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TAKING ADVANTAGE OF EMERGING
TECHNOLOGIES IN CLINICAL PRACTICE
This volume includes the proceedings of the
Thirty-Eighth Annual Moyers Symposium
February 26–27, 2011
Ann Arbor, Michigan
Editor
James A. McNamara, Jr.
Associate Editor
Kristin Y. De Koster
Volume 49
Craniofacial Growth Series
Department of Orthodontics and Pediatric Dentistry
School of Dentistry; and
Center for Human Growth and Development
The University of Michigan
Ann Arbor, Michigan
©2012 by the Department of Orthodontics and Pediatric Dentistry,
School of Dentistry and
Center for Human Growth and Development
The University of Michigan, Ann Arbor, MI 48109
Publisher’s Cataloguing in Publication Data
Department of Orthodontics and Pediatric Dentistry and
Center for Human Growth and Development
Craniofacial Growth Series
Taking Advantage of Emerging Technologies in Clinical
Practice
Volume 49
ISSN 0.162 7279
ISBN 0-929921-00-3
ISBN 0-92992.1–45–3
No part of this publication may be reproduced, stored in a retrieval system, or
transmitted in any form by any means, electronic, mechanical, photocopying,
recording, or otherwise, without the prior written permission of the Editor-in-
Chief of the Craniofacial Growth Series or designate.
DEDICATION
Photograph: Per Kjeldsen.
It is with great sadness that we dedicate this volume to our close
friend and colleague, Dr. Tiziano Baccetti, who died in a tragic accident in
Prague on November 25, 2011. Tiziano just had given a “brilliant, energetic
and humorous” keynote address at the 9th International Orthodontic Sympo-
sium for which he received a standing ovation.
Tiziano had a long history with the Moyers Symposium, beginning
in 1995. He appeared at least a dozen times on the Symposium and Pre-
Symposium programs over the years, the last time in 2010 (see photo). He
was the most frequent contributor to the Craniofacial Growth Monograph
Series since its inception in 1975, including two chapters in this volume.
Tiziano was Assistant Research Professor in the Department of Or-
thodontics at the University of Florence. He also was Thomas M. Graber
Visiting Scholar in the Department of Orthodontics and Pediatric Dentistry
at Michigan. He had a continuing impact on our orthodontic residents, both
during their residency and afterwards, as well as our faculty and staff.
Tiziano had friends and collaborators worldwide with whom he
shared his enthusiasm for life. He was a charismatic individual who had an
impact professionally and personally far greater than his years. Tiziano was
One of a kind – there is a hole in our hearts with his passing.

CONTRIBUTORS
ABEER ALHADIDI, Post-Doc Research Associate, Department of Di-
agnostic Sciences, University of North Carolina, Chapel Hill, NC.
DANIEL E. ATKINS, W.K. Kellogg Professor of Community Infor-
matics, Professor of Electrical Engineering and Computer Science, Asso-
ciate VP for Research Cyberinfrastructure, The University of Michigan,
Ann Arbor, MI.
TIZIANO BACCETTI, deceased, former Assistant Research Professor,
Department of Orthodontics, The University of Florence, Florence, Italy;
former Thomas M. Graber Visiting Scholar, Department of Orthodontics
and Pediatric Dentistry, School of Dentistry, The University of Michi-
gan, Ann Arbor, MI.
SHELDON BAUMRIND, Professor, Department of Orthodontics, Uni-
Versity of the Pacific, San Francisco, CA.
LUCIA H.S. CEVIDANES, Assistant Professor, Department of Ortho-
dontics and Pediatric Dentistry, School of Dentistry, The University of
Michigan, Ann Arbor, MI.
CAUBY MAYA CHAVES JR., Associate Professor, Department of
Orthodontics, School of Dentistry, Universidade Federal do Ceará, Bra-
zil; Visiting Researcher, Department of Orthodontics and Pediatric Den-
tistry, School of Dentistry, The University of Michigan, Ann Arbor, MI.
LUCA CONTARDO, Assistant Professor, Department of Medical, Sur-
gical and Health Sciences, School of Dentistry, University of Trieste,
Trieste, Italy.
SEAN CURRY, Technical Advisor, UOP and AAOF Legacy Growth
Collection, Talent, OR; private engineering consultant, Talent, OR.
ADRIANA DA SILVEIRA, Chief of Orthodontics, Dell Children’s
Craniofacial & Reconstructive Center, Austin, TX; Adjunct Professor,
University of Texas at Austin, Department of Biomedical Engineering,
Austin, TX.
WILLIAM D. ENGILMAN, Clinical Instructor, Department of Ortho-
dontics, University of Louisville, Louisville, KY; private practice, Lou-
isville, KY.
LORENZO FRANCHI, Assistant Professor, Department of Ortho-
dontics, The University of Florence, Florence, Italy; Thomas M. Graber
Visiting Scholar, Department of Orthodontics and Pediatric Dentistry,
School of Dentistry, The University of Michigan, Ann Arbor, MI.
LAURA R. IWASAKI, Associate Professor, Division of Orthodontics
and Dentofacial Orthopedics, School of Dentistry, University of Missouri
– Kansas City, Kansas City, MO.
LYNN A. JOHNSON, Professor and Assistant Dean for Dental Infor-
matics and Innovation, School of Dentistry, The University of Michigan,
Ann Arbor, MI.
GREG JORGENSEN, private practice of orthodontics, Rio Rancho,
NM.
OLEG KROKHIN, Assistant Professor, Department of Internal Medi-
cine, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba,
Canada.
MANUEL O. LAGRAVERE VICH, Clinical Assistant Professor, Uni-
Versity of Alberta, Orthodontic Graduate Program, Edmonton, Alberta,
Canada.
JAMES A. McNAMARA JR., Thomas M. and Doris Graber Endowed
Professor, Department of Orthodontics and Pediatric Dentistry, School of
Dentistry; Professor, Cell and Developmental Biology, School of Medi-
cine; Research Scientist, Center for Human Growth and Development,
The University of Michigan, Ann Arbor, MI.
MARY KAY MILLER, Internet Marketing and Website Consultant,
Orthopreneur Marketing Solutions, East Rochester, NY.
MAJA OVSENIK, Professor, Department of Dental and Jaw Orthopae-
dics, University of Ljubljana, Ljubljana, Slovenia.
BEATRIZ PANIAGUA, Department of Computer Science, University
of North Carolina, Chapel Hill, NC.
GIUSEPPE PERINETTI, Research Associate, Department of Medical,
Surgical and Health Sciences, School of Dentistry, University of Trieste,
Trieste, Italy.
JASMINA PRIMOZIC, Medical Faculty, Department of Dental and
Jaw Orthopaedics, University of Ljubljana, Ljubljana, Slovenia.
WELLINGTON J. RODY JR., Assistant Professor, Division of Ortho-
dontics, Faculty of Dentistry, University of Manitoba, Winnipeg, Mani-
toba, Canada.
CRAIG SCHOLZ, Director of Emerging Technology, Orthod II Com-
puter Systems, Ames, IA. -
ROBERT P. SCHOLZ, Editor, Technobytes, American Journal of Or-
thodontics and Dentofacial Orthopedics, Discovery Bay, CA.
KIRT E. SIMMONS, Director, Craniofacial Orthodontics, Arkansas
Children’s Hospital, University of Arkansas Medical School, Little
Rock, AR.
RONALD J. SNYDER, private practice of orthodontics, Apple Valley,
MN.
MARTIN STYNER, Department of Computer Science, University of
North Carolina, Chapel Hill, NC.
PREFACE
The generation of patients seeking any kind of medical or dental
care today research and read on the Internet, using websites and social
networking as significant factors in how they decide on what kind of care
to seek and where. Communication has moved from snail mail and the
telephone to the Internet, fiberoptics, instant messaging and social net-
Working. On the horizon is the electronic patient record that is accessible
by involved clinicians anytime, anywhere (cloud computing) as well as
accessing the record with mobile devices and Voice-over Internet Proto-
col (VoIP). In addition, we have seen the DICOM files of cone-beam CT
and the STL files of the surfaces of the dentition and adjacent soft tissue
Structures become part of routine patient care in some offices, along with
Computer-assisted treatment planning of patients undergoing corrective
Surgical procedures.
The topic of emerging technologies in clinical practice was ad-
dressed during the 38" Annual Moyers Symposium, which was held at the
University of Michigan on Saturday, February 26, and Sunday, February
27, 2011. In past years, the focus of the Symposium has been primarily
Orthodontics and craniofacial biology; this year we broadened the scope
of the Symposium to include all providers of patient care.
The Presymposium (actually the 37th Annual International Con-
ference on Craniofacial Research) was held on February 25, 2011 in the
4th Floor Amphitheater of the Horace H. Rackham Building. This meet-
ing featured papers relevant to orthodontics, technology and craniofacial
biology that were presented by an international group of investigators.
Several of these papers that were relevant to the topic of technology are
included as chapters in this volume.
As in previous years, the Symposium honored the late Dr. Robert
Edison Moyers, Professor Emeritus of Dentistry and Fellow Emeritus
and Founding Director of the Center for Human Growth and Develop-
ment at the University of Michigan. This meeting was co-sponsored by
the School of Dentistry and the Center for Human Growth and Develop-
ment.
We want to recognize the enormous contribution of Kris De Koster,
the Associate Editor of the Craniofacial Growth Series, for her efforts on
this book. For the past four years, Kris has facilitated the publication of
this annual volume through her interacting with the authors, editing, ma-
nipulating a variety of figure formats and formatting the layout of the
book. It is always a challenge for us to produce such a volume in the time
frame prior to the next Symposium; Kris has a stellar record of producing
a high quality book within this limited period of time.
We thank the contributors for sending us their material in a
timely fashion. We also recognize Lauren Sigler, our former research
assistant and now dental student at the University of Michigan, for her
help in validating the references provided by the contributors.
We acknowledge Sunil D. Kapila, the Chair of the Department
of Orthodontics and Pediatric Dentistry, for providing the financial re-
sources to underwrite partially the publication of this book. We also must
thank Twila Tardif, the Director of the Center for Human Growth and
Development, for the continued financial and moral support of the Moy-
ers Symposium provided by the Center. s
We continue to be fortunate in working with the same staff from
the Office of Continuing Dental Education in their organizing and run-
ning the Presymposium and Symposium. We thank Michelle Jones,
Debbie Montague and Karel Barton for managing both meetings in such
a smooth and efficient fashion. We wish Debbie good fortune in the fu-
ture following her retirement from the School of Dentistry earlier this
year.
James A. McNamara
Ann Arbor, Michigan
November, 2011
FRIENDS OF THE SYMPOSIUM
Chester S. Handelman
Robert J. Isaacson
Katherine A. Kelly
William Womack
TABLE OF CONTENTS
Contributors
Preface
Friends of the Symposium
Dedication
The Emergence of Cyberinfrastructure-enabled Discovery
and Learning
Daniel E. Atkins
The Electronic Patient Record: How It Affects the Private
Practitioner
Kirt E. Simmons
Social Media: What Every Clinician Should Know
Greg Jorgensen
Connecting the Dots: Are You Up to Speed Integrating Your
Internet Marketing Plan?
Mary Kay Miller
Mobile Device Trends
William D. Engilman
A Telecommunications Primer
William D. Engilman
Cloud Computing in Dentistry
Lynn A. Johnson
Cloud Computing
Craig Scholz
New Tech for Dummies
Robert P. Scholz
The Use of 3D Imaging to Advance Your Practice
Lucia H.S. Cevidanes, Cauby Maya Chaves Jr.,
Abeer Alhadidi, Martin Styner, Beatriz Paniagua
3D Virtual Surgical Planning for Orthognathic Surgery
Adriana Da Silveira
19
33
55
81
105
115
123
133
155
Landmarks in Three-dimensional Imaging, Development and
Usage
Manuel O. Lagravere Vich
Gingival Crevicular Fluid as a Source of Biomarkers of
Patient Responsiveness to Orthodontic Treatment
Giuseppe Perinetti, Luca Contardo, Tiziano Baccetti
Oral Fluid-based Diagnostics and Applications in
Orthodontics
Wellington J. Rody Jr., Laura R. Iwasaki, Oleg Krokhin
Suresmile". An Eight-year Clinical Perspective
Ronald J. Snyder
Using Facial Laser Scanning for Assessing Facial Symmetry:
A Prospective Study in Children Affected by Crossbite
Jasmina Primožić, Tiziano Baccetti, Lorenzo Franchi,
Maja Ovsenik
The AAOF Craniofacial Growth Legacy Collection:
A Powerful New Tool for Orthodontic Teaching and
Research
Sheldon Baumrind and Sean Curry
| 7 |
| 97
223
263
281
297
THE EMERGENCE OF CYBER-
INFRASTRUCTURE-ENABLED DISCOVERY
AND LEARNING
Daniel E. Atkins
ABSTRACT
Cyberinfrastructure is increasingly an indispensable platform for the academic
enterprise of discovery, learning and practice, with healthcare being no excep-
tion. Although the raw capacity of the technology continues to grow exponen-
tially, the socio-technical challenges of adoption move much more slowly. The
challenge and opportunities for universities is the ability to use cyberinfrastruc-
ture as a platform for enhancing authentic knowledge communities and expand-
ing their scope and participation in time and distance. The knowledge commu-
nity model stresses the interconnection between learning about, learning to do
and learning to be a member of a community of practice. The provisioning and
application of cyberinfrastructure in universities should be guided by the goal to
enhance these three types of activities and their synergistic interaction. In this
chapter, the author suggests a more comprehensive model for the role of cyber-
infrastructure to support distributed knowledge-based activities including re-
search, training and practice in orthodontics. Using a four-quadrant model of
collaboration, the author argues that a cyberinfrastructure platform that makes
use of the four modes of collaboration (same time, same location; same time,
different location; different time, same location; different time, different loca-
tion) offers the opportunity to structure or restructure the flow of work to opti-
mize the overall effectiveness of the organization. Cyberinfrastructure used to
support four-quadrant knowledge communities is the key to Scaling up access to
higher education in ways that never will be possible in a predominantly bricks
and mortar university model.
KEY WORDS: cyberinfrastructure, collaboration, universities in the digital age,
four-quadrant organizations
Although many technologies have transformed the course of
human history, the pace and impact of digital information technology are
unprecedented. In little more than half a century, we have moved from
mammoth computer temples with the compute power of a digital wrist
Cyberinfrastructure-enabled Discovery
watch to an ecosystem of billions of microelectronic computation devi-
ces, linked together at nearly the speed of light and executing critic com-
plex programs with astronomical quantities of data. The merger of digital
computing, communication and storage has produced critical infrastruc-
ture now often referred to as cyberinfrastructure. Cyberinfrastructure is
increasingly an indispensable platform for the academic enterprise of
discovery, learning and practice, and healthcare is no exception. Al-
though the raw capacity of the technology continues to grow exponen-
tially, the socio-technical challenges of adoption move much more
slowly. We are just beginning to exploit the transformative potential in
all lines of knowledge-based activities including orthodontic research,
education and practice.
The National Science Foundation',(NSF) has been a leader in
enabling the creation and use of cyberinfrastructure for open scientific
research and education. It supported universities in the purchase of time-
shared mainframe computers and more recently has funded a portfolio of
supercomputer centers as a national resource. The NSF also played a
seminal role in the transfer of the experimental Advanced Projects Re-
search Agency (ARPA, 2011) net into the more inclusive National Sci-
ence Foundation Network (NSFNET, 2011), which in turn sparked the
creation of the modern ubiquitous Internet as we now know it. Through a
series of investments in digital library research, the NSF accelerated the
dominance of the digital information revolution and laid the technologi-
cal groundwork for Google. Research in computer science has provided
the seeds for much of the digital technology commonly used today.
Nanotechnology research has contributed to breakthroughs in sensor
technology that are revolutionizing scientific instrumentation.
In the 1980s, the NSF research community began to realize that
the integration of computing, communication, sensing and activation
technologies offered the potential for “laboratories without walls” that
could be connected but geographically distributed to relax the constraints
of distance and time in collaborative, often interdisciplinary, research.
The NSF also realized that there were both significant technical and so-
cial challenges to be solved in order to reach the full potential of the col-
laboratory and change what research is possible, how research is done
and who participates. The collaboratory has evolved as both a means to
support research as well as an object of research, building upon the fields
of computer-supported cooperative work (CSCW), human-computer in-
teraction (HCI) and, more recently, social networks. From this perspec-
Atkins
tive, high-performance computing is part of a larger opportunity to use
cyberinfrastructure as a platform for high-performance collaboration.
The term collaboratory was coined in 1989 to describe this new
type of cyberinfrastructure-enabled research environment (Wikipedia,
2011). It was defined more fully and endorsed in 1993 with a report from
the National Academies of Science. The NSF issued a report (Atkins et
al., 2003) from a Blue Ribbon Panel that made an even stronger claim
for the potential for collaboratories and more generally for cyberinfra-
structure, namely that it had the potential to revolutionize science and
engineering. p
Although this term has become used widely (1.6 million hits in a
Google search conducted in August, 2011), numerous other terms are
used for similar concepts including science gateway (104,000 Google
hits), science hub (241,000 Google hits) and virtual research environ-
ment (220,000 Google hits). Collaboratories also are related closely to
distance learning, telemedicine and similar concepts beginning with “dis-
tance” or “tele.” Prefixes such as “virtual-,” “distance-” or “tele-” often
suggest a downgraded sense of participation or even a desire to eliminate
the need for physical presence.
In this chapter, the author suggests a more comprehensive model
for the role of cyberinfrastructure to support distributed knowledge-based
activities including research, training and practice in orthodontics. It ar-
gues for the use of the term all-quadrant organizations instead of terms
like virtual organization because this broader term subsumes the concept
of virtual organization and does not exclude collaboration at the same
time in the same place.
Figure 1 is a two-by-two matrix illustrating all four variations of
collaboration in the same and different times and locations. People (P)
can communicate at the same time in the same location (ST-SL); at a
different time in different locations (DT-DL) through, for example,
email; at the same time and different locations (ST-DL) through, for ex-
ample, video conferencing; or at different time and the same location
(DT-SL) through working together at a fixed location at different times
to build an object or treat a patient in a hospital room.
In addition to linking people to communicate, cyberinfrastructure
can link information (I) and facilities or tools (F) in all of these quadrants
to enable knowledge work to be done by teams, over and above discuss-
ing work together. For example, geographically distributed researchers can

Cyberinfrastructure-enabled Discovery
Time
Same Different
(synchronous) (asynchronous)
P. Physical meetings P. Shared physical artifact
..º. Same || Physical books,journals º...
-- c. FWetlabs, studios, shops º
º-.9 abs
§§
O P. Email
§ 3 P:AM conference |-intelligent agents
O Different EWeb search - gent ag
F-Autonomous
observatories
|
Key: P:People, Enformation, F. Facilities
F: Online instruments
Figure 1. Four- or all-quadrant organizations offer additional modes of
interaction between people, information and facilities.
operate online observatories remotely together in real time in what they
call “campaign mode” and later federate and analyze these data from
these instruments at different times in different places. Distributed teams
can collaborate to design a physical object and then fabricate it at an on-
line facility. The ST-SL quadrant still will remain the most precious
quadrant (and perhaps the most expensive), but cyberinfrastructure pro-
vides three other quadrants for collaboration that people and organiza-
tions may need to adopt to remain competitive.
A cyberinfrastructure platform offers the opportunity to structure
or restructure the flow of work to optimize the overall effectiveness of
the team using all four quadrants of the workflow. Keeping in mind that
the ST-SL quadrant often is the most precious of the quadrants, the other
three quadrants can be used to increase the benefit of the time that people
have together face to face. Rather than advocating for either virtual or
physical, we are advocating virtual plus physical. How can knowledge
communities use not just physical presence, not just virtual presence, but
rather all four quadrants systematically for maximum benefit? The chal-
lenge is to discover within a particular community the nature of the ca-
pabilities needed and how the workflow of the community best maps on
to or flows through the four quadrants.
So far the design of specific collaboratories has focused on sup-
porting the needs of small teams of two to ten members. Researchers typ-
Atkins
ically work with a network of small teams often overlapping in member-
ship with individuals playing varying roles in various teams such as
leader, member or observer. The two-by-two matrix (Fig. 1), therefore,
has a third dimension, namely the interoperability between specific four-
quadrant collaboratories associated with specific teams with specific sets
of information, tools and facilities.
The activities of organizations are performed by many overlap-
ping and interoperable teams of people such as those in a university or
healthcare delivery system. The promise of cyberinfrastructure is to en-
able these teams to carry out their mission more effectively and poten-
tially even expand their mission by becoming all-quadrant organizations.
For example, the large lecture hall experience for students is not neces-
sarily the best use of their face-to-face (ST-SL) time. If the lectures were
recorded allowing students to learn the material in different places at dif-
ferent times, than the face-to-face time could used for small group inter-
action. Applied to a global level, it is easy to imagine lab facilities acces-
sible to all students regardless of time or place, thereby giving students in
developing countries access to first-rate facilities.
As mentioned earlier, collaborating at ST-SL often is regarded as
the best form of collaboration, while virtual or remote participation is
considered less desirable. With regard to computer-supported collabora-
tive work, however, there is the concept of “beyond being there” (Hollan
and Stornetta, 1992) or “better than being there” that asserts that the re-
sults of collaboration in some instances can be better in distributed set-
tings than in physical proximity.
One example is the possible advantage of anonymity. Cyberin-
frastructure-enabled anonymous discussions have been shown to lead to
more frank deliberations that are less dominated by the boss than are
those conducted in a more traditional setting. It also enables anonymous
role-playing in educational games for people who may otherwise be un-
convincing in physical presence. For example, Professor Frederick
Goodman at the University of Michigan used cyberinfrastructure to con-
nect schools around the world for intensive, term-long exercises such as
a simulation of the Arab-Israeli conflict. Acting anonymously, young
inner-city schoolgirls were effective in playing the role of Arafat in ways
that would not have been possible in physical presence. The 2008 NSF
report entitled Beyond Being There: A Blueprint for Advancing the De-
sign, Development and Evaluation of Virtual Organizations elaborates
such opportunities.
Cyberinfrastructure-enabled Discovery
Cyberinfrastructure is having a profound impact on the conduct
of science and making significant inroads into the humanities. The emer-
gence of “web 2.0” (the shift from information to the information plus
participation), together with the movement toward open educational re-
Sources and the increasing ubiquity of broadband networks, are brewing
a perfect storm of opportunites for open, participatory learning. Cyberin-
frastructure, for example, is playing a significant role in the National
Education Technology Policy (NETP, 2010) report from the Obama
White House entitled, Transforming American Education: Learning
Powered by Technology. The report outlines cyberinfrastructure-enabled
opportunities around assessment by measuring what matters, teaching by
improving learning through connected learning and productivity by en-
hancing learning outcomes while managing costs.
The challenges and opportunities for universities is the ability to
use cyberinfrastructure as a platform for enhancing authentic knowledge
communities and for expanding their scope and participation in time and
distance. The knowledge community model stresses the interconnection
between learning about, learning to do and learning to be a member of a
community of practice. The provisioning and application of cyberinfra-
structure in universities should be guided by the goal to enhance these
three types of activities and their synergistic interaction. Universities are
fundamentally about participation in authentic knowledge communities;
it is the collection of communities that universities open to their students
as much as their formal pedagogy that make them such valuable sites for
learning.
Finally, all-quadrant knowledge communities hold the promise
to scale up access to higher education for the growing number of people
worldwide who are qualified to enter a university but for whom none is
available. Sir John Daniels, former Vice-Chancellor of the Open Univer-
sity in the U.K. and now CEO of the Commonwealth of Learning (Van-
couver, Canada), offers the following eye-opening data:
• Half of the world’s population is under 20 years old.
• Today, there are over 30 million people qualified to
enter a university, but no place available. During the
next decade, this number will grow to 100 million.
• In most of the world, higher education is mired in a
crisis of access, cost and flexibility. The dominant
forms of higher education – campus-based, high cost,
Atkins
limited use of technology – seem ill-suited to address
global education needs in the decades ahead.
• To meet this staggering global demand, a major uni-
versity needs to be created every week.
Cyberinfrastructure used to support all-quadrant knowledge
communities is the key to scaling up access to higher education in ways
that will never be possible in a predominantly bricks and mortar univer-
sity model.
REFERENCES
“ARPANET.” Wikipedia, The Free Encyclopedia. Wikimedia Founda-
tion Inc., August 2011. http://en.wikipedia.org/wiki/ARPANET
Atkins DE, Droegemeier KK, Feldman SI, Garcia-Molina H, Klein ML,
Messerschmitt DG, Messina P, Ostriker JP, Wright MH. Revolution-
izing science and engineering through cyberinfrastructure: Report of
the NSF blue-ribbon advisory panel on cyberinfrastructure. 2003: 1-
84. http://www.nsf.gov/od/oci/reports/atkins.pdf
Building Effective Virtual Organizations: An NSF workshop. Washing-
ton DC, January 14–16, 2008. www.ci.uchicago.edu/events/VirtOrg
2008/
“Collaboratory.” Wikipedia, The Free Encyclopedia. Wikimedia Foun-
dation Inc., August 2011. http://en.wikipedia.org/wiki/Collaboratory
Hollan J, Stornetta S. Beyond Being There. Proceedings of the SIGCHI
conference on the human factors in computing systems. Chicago
1992. http://scholar.google.com/scholar?q=%22beyondtbeing Hthere
%22&hl=en&as_sdt =0&as_vis-1&oi=scholart
National Collaboratories: Applying Information Technology for Scien-
tific Research. Washington, DC: National Academy Press 1993.
http://www.nap.edu/openbook.php?record_id=2109&page=79
“National Science Foundation Network.” Wikipedia, The Free Encyclo-
pedia. Wikimedia Foundation Inc., August 2011. http://en.wiki-
pedia.org/wiki/National_Science Foundation Network
National Education Technology Plan 2010. U.S. Department of Educa-
tion. http://www.ed.gov/technology/netp-2010
THE ELECTRONIC PATIENT RECORD: HOW IT
AFFECTS THE PRIVATE PRACTITIONER
Kirt E. Simmons
ABSTRACT
An electronic patient record (electronic digital form of a health record) includes:
electronic medical record (EMR), electronic dental record (EDR), electronic
health record (EHR) and personal health record (PHR). With EMRS/EDRS (the
electronic form of paper charts classically used), information does not travel
easily out of a practice, while an EHR is a longitudinal electronic record of
health information generated by multiple encounters in any care delivery setting.
An EHR is “built” to share information on the patient between health facili-
ties/providers, so all involved can access it. The EHR reaches out beyond health
organizations that originally collected information and ideally includes all den-
tal, medical and other records in essentially “real time” and is “qualified” and
“certified” by the government. A PHR is a patient-created electronic record that
conforms to certain interoperability standards (same as EHRs), therefore allow-
ing PHRs and EHRs to interact. The primary factor “driving” change to EHRs is
the Health Information Technology for Economic and Clinical Health Act
(2009), with an objective of providing health care providers accurate and com-
plete information about a patient's health, so they can give safer care at lower
costs (with implementation by 2016). The Act provides incentive payments to
eligible professionals to adopt, implement, upgrade or demonstrate meaningful
use of certified EHR. It also specifies new privacy, security and accessibility
provisions for all healthcare providers. Besides government promotion, it is be-
coming obvious that third party payers, many malpractice/liability insurers, pri-
vacy/security regulations, pharmacies/DEA and new (or updates to) imaging
hardware/software may require their clients to be EHR compliant.
KEY WORDS: electronic patient record, electronic health record, personal health
record, electronic dental record
INTRODUCTION
Prior to engaging in a discussion of the electronic patient record
(EPR), it is imperative to provide some definitions, as there are some
Electronic Patient Records
common discrepancies in the terms associated with the electronic patient
record. An electronic patient record is simply an electronic or digital
form of a health record, including the following examples and their ab-
breviations/acronyms: electronic medical record (EMR), electronic den-
tal record (EDR), electronic health record (EHR) and personal health
record (PHR). A word about acronyms is appropriate now, since the U.S.
Federal Government Agencies, including the Office of the National Co-
ordinator for Health Information Technology (ONC), are enamored with
acronyms; they use acronyms in their definitions of other acronyms and
even as part of other acronyms. On the ONC website, for instance, there
are five web pages of Health Information Technology (HIT) acronyms
(see www.healthit.hhs.gov).
What are the different forms of electronic patient records? An
electronic medical record (EMR) is simply an electronic form of the pa-
per medical charts classically used in a clinician’s office and contains the
medical and treatment history of the patients in a single practice. The
EMR allows clinicians to track clinical/financial/other data over time and
easily identifies patients due for preventive screenings or checkups. The
EMR also allows the clinician to check certain patient parameters – such
as blood pressure readings or vaccinations – and potentially to monitor
and improve the overall quality of care within that practice. The major
problem with an EMR is that information contained within it does not
travel easily out of the practice.
An electronic dental record (EDR) is simply the dental equiva-
lent to the EMR; this term describes what almost all dental professionals
who are using “electronic records” currently are keeping. It contains the
dental and treatment history of patients in one practice (although this
may be a large group practice with multiple clinicians). It has the same
problem as an EMR in that information in the EDR does not travel easily
out of the practice and typically does not integrate with other medical
data.
An electronic health record (EHR) is a longitudinal electronic
record of patient health information generated by one or more encounters
in any care delivery setting. Included in this information are patient
demographics, progress notes, problems, medications, Vital signs, past
medical history, immunizations, laboratory data and radiology reports
(per the Healthcare Information and Management Systems Society, or
HIMSS). The EHR focuses on the total health of the patient in that it
reaches out beyond the health organizations (clinicians’ offices or hospi-
tals) that originally collect the information. They are built to share infor-
10
Simmons
mation with other health care providers and the information moves with
the patient between health facilities/providers. In addition, EHRs are de-
signed to be accessed by all persons involved in a patient’s care, includ-
ing the patients themselves. Indeed, that is an explicit expectation in the
Stage 1 definition of “meaningful use” of EHRs (“meaningful use” is a
term developed by the ONC to describe use sufficient to apply for funds
set aside to increase EHR adoption). An EHR ideally would include all
dental, medical, pharmacy, chiropractic and other records in essentially
“real time” and be “qualified” and “certified” as such.
A “qualified” EHR, per Section 3000, Definitions, of Subtitle A,
Part 1, of Title XIII in the American Recovery and Reinvestment Act
(ARRA) of 2009, includes an electronic record of health-related informa-
tion on an individual that contains patient demographic and clinical
health information, such as medical history and problem lists, and has the
capacity to:
• Provide clinical decision support;
• Support physician order entry;
• Capture and query information relevant to health care
quality; and
• Exchange electronic health information with and in-
tegrate such information from other sources.
Many advantages have been touted for EHRs. Among these are
their ability to consolidate all dental, medical, pharmacy, chiropractic
and other records in a single location; their ability to allow emergency
departments to be aware quickly of any life threatening conditions, even
if the patient is unconscious; the ability of a patient to log on to his/her
own record and see the trend of lab results over a period of time, which
can help motivate patients to take their medications and keep up with the
lifestyle changes that have improved the numbers; and the ability of the
EHR to be stored offsite securely so it is not lost in disasters (i.e., hurri-
canes, tornados, fires).
Other features include: lab results run last week already are in
the record for a specialist to access without running duplicate tests; pre-
scriptions, notes and orders are legible; notes from a hospital stay can
help inform discharge instructions and follow-up care, especially if the
patient will be followed up in a different (more local) care setting; pa-
tients seeing new clinician/clinic do not have to enter their/their child’s
information or carry paper copies with them; and public health officials
and researchers more readily can be alerted to, respond to and research
11
Electronic Patient Records
illness trends (SARS, Swine Flu, influenza), treatment differences, out-
comes differences and the like.
A personal health record (PHR), sometimes called a patient-
controlled health record (PCHR), is a patient-created electronic record
that conforms to certain interoperability standards (the same as EHRs). It
can be drawn from multiple sources and is managed, shared and con-
trolled by the individual patient. The patient may or may not choose to
grant other entities access to it in that the PHR is controlled by the pa-
tient (unlike EHRs). The intent is to allow PHRs and EHRs to interact if
desired and allowed by the patient.
There are many factors currently driving the change to EHRs:
Congress, The American Recovery and Reinvestment Act (ARRA) of
2009 (including the Health Information Technology for Economic and
Clinical Health Act [HITECH]), the President, Third Party Payers (e.g.,
Medicaid, insurance companies), technology and software vendors,
Standards Organizations [DICOM, HL7], public demand (in response to
natural disasters), researchers and public health organizations.
One of the most prevalent of these driving forces is the HITECH
Act. The objectives of the HITECH Act are to leverage health informa-
tion technology (IT) so health care providers will have:
• Accurate and complete information about a patient's
health so they can give the best possible care, whether
during a routine visit or in a medical emergency;
• The ability to better coordinate the care they give (es-
pecially important if a patient has a serious medical
condition);
• A way to share information securely with patients and
their family caregivers over the Internet (for patients
who opt for this convenience); and
• The chance to allow patients and their families to take
part in decisions about their health care more fully.
Per the framers of this legislation, this increased access to health infor-
mation will help clinicians diagnose health problems sooner, reduce
medical errors and provide safer care at lower costs. This legislation also
claims widespread use of health IT can make our health care system
more efficient, reduce paperwork for patients and doctors, expand access
to affordable care and build a healthier future for our nation.
12
Simmons
The overseer of the EHR in the U.S. is the Office of the National
Coordinator for Health Information Technology (ONC). This office was
set up to support adoption of health IT and promotion of a nationwide
health information exchange to improve health care. The ONC is part of
the Office of the Secretary for the U.S. Department of Health and Human
Services (HHS). It is directed by the position of National Coordinator of
the ONC and was created in 2004, through an Executive Order and legis-
latively mandated in the HITECH Act of 2009.
Important issues include how the EPR will be accessed and
where it will be stored. Individual PHRs will be kept by patients and
stored by them (USB, CD, DVD). For EHRs, several potential options
have been proposed, including the National Health Information Network
(NHIN), an as yet unidentified national repository, or within Health In-
formation Exchanges (HIES) that are specific regional/area/network re-
positories.
The details of storage have not yet been finalized at this time, but
such storage will require standards for accessibility of the data, whether
in a single, central repository or in multiple HIES.
The NHIN was formed to create a common platform for health
information exchange across diverse entities, within communities and
across the country. Its purpose was to promote a more effective market-
place, greater competition and increased choice through accessibility to
accurate information on health care costs, quality and outcomes. In es-
sence, this is what generally is thought of as the “ideal”: a single, na-
tional, all-inclusive database for all citizens. An HIE, on the other hand,
is a state or regional program set up to ensure the development of health
information exchange within and across their jurisdictions.
The HIEs currently are being advanced as a more readily imple-
mented means of meeting the aggressive EHR implementation timelines.
Of course, in order for different HIEs to be able to interact and “play
well” with each other, they all need to be “speaking the same language,”
which requires accepted standards. The standards that are relevant for
EHRs include the Digital Imaging and Communication in Medicine (DI-
COM) standard that is the established standard for the exchange of digi-
tal information between medical imaging equipment (i.e., radiographs,
photographs, digital models, cone-beam computed tomography) and
other systems. Hospitals long have used the DICOM standard in their
radiology departments, which allows any type of radiograph obtained at
one hospital to be transported, accessed and used at any other hospital,
13
Electronic Patient Records
regardless of their radiologic software program. Another EHR standard
in use is the Health Level 7 (HL7) standard, which is the established
standard for data exchange, management and integration to support clini-
cal patient care as well as the management, delivery and evaluation of
healthcare service (i.e., billing, demographics, outcome measures).
What is the timeline of the EHR'? In his 2004 State of the Union
address, President George W. Bush set as a goal for most Americans to
have a universal EHR by the year 2014. In 2009, Congress passed the
ARRA and HITECH legislation, which established further guidelines for
the development, adoption and implementation of the EHR. Per this leg-
islation, by 2010 the rules, definitions (especially for “meaningful use” –
a term used in the legislation), certification process and certification bod-
ies were identified and developed. *
In 2011, Stage 1 of the implementation process will be com-
pleted. Stage 1 consists of “Data Capture,” the electronic capture of
health care information in a standardized format. In 2013, Stage 2,
known as “Data Aggregation,” electronic exchange of the collected
health information will occur in order to improve the quality of care. In
2015, Stage 3, “Data Use for Outcome Impact” will be used as needed to
improve the quality, safety and efficiency of healthcare through clinical
decision support (CDS) and patient management tools.
By 2016, full implementation (i.e., all healthcare providers will
fully be using and all persons will have an EHR) will be completed. The
legislation initially provides for financial incentives if healthcare provid-
ers/organizations “qualify,” but these incentives quickly change to disin-
centives for those who do not comply. For instance, in 2011 healthcare
providers who do not begin e-prescribing drugs (i.e., “writing” a certain per-
centage of their prescriptions) will have payments reduced through Medicaid.
This discussion leads to consideration of the Medicaid EHR In-
centive Program legislated by the HITECH Act. This program provides
incentive payments to eligible professionals and eligible hospitals as they
adopt, implement, upgrade or demonstrate meaningful use of certified
EHR technology in their first year of participation and demonstrate
meaningful use for up to five remaining participation years. There are
minimum Medicaid patient volumes to be eligible, which differs by state.
The program is offered voluntarily by individual states and territories and
begins as early as 2011, depending on the state.
14
Simmons
Eligible professionals (including dentists) can receive up to
$63,750 in funds over six years if they choose to participate in the pro-
gram and meet all requirements. There are no payment adjustments un-
der the Medicaid EHR Incentive Program. By contrast, just to be confus-
ing, the Medicare EHR Incentive Program provides incentive payments
to eligible professionals and hospitals that demonstrate meaningful use of
certified EHR technology.
Participation in the Medicare Program can begin as early as
2011, with eligible professionals able to receive up to a maximum of
$44,000 over five years under the Medicare EHR Incentive Program for
treating patients who qualify under Medicare. In addition, if the eligible
professionals provide services in a Health Professional Shortage Area
(HPSA), they qualify for additional incentives above the $44,000 maxi-
mum under the Medicare EHR Incentive Program.
For maximum incentive payment, Medicare-eligible profession-
als must begin participation by 2012. For 2015 and later, Medicare eligi-
ble professionals who do not demonstrate meaningful use successfully
will have a “payment adjustment” (read: reduced payment or penalty) in
their Medicare reimbursement. In order to qualify for these Medi-
caid/Medicare EHR Incentive Programs, eligible healthcare providers
must use a certified EHR program and demonstrate meaningful use of
the program for their patients. For dentistry, as of early 2011, only one
EHR dental software program meets the federal guidelines and has been
certified as such.
A reasonable question for most dentists might be “Who cares?”
There is no federal deadline for adoption of EHRs by dentists who do not
submit claims to Medicare; the thought can be, “Since I do not mess with
Medicare/Medicaid, it is not going to affect me.” Unfortunately, although
you may not “mess” with the public payer programs, the legislation is
going to “mess” with you! Specifically, new privacy and security provi-
sions (on top of current HIPAA requirements) and accessibility require-
ments are among the ARRA/HITECH legislation provisions, including:
• Privacy and security provisions extended to “business
associates” (e.g., laboratories);
* Breach notification requirements;
* Health information privacy education requirements
for your staff;
15
Electronic Patient Records
• A requirement to honor withholding of protected
health information from a health plan when a patient
pays for treatment “out of pocket;”
• A prohibition of the sale of protected health information;
* A requirement for patient authorization for marketing
and fundraising-related activities;
* New accessibility requirements to patient information
(i.e., patients may request an electronic copy of their
record and it must be provided and in a timely fash-
ion); and
• It authorizes patients the right to request an “audit
trail” of all access to their record (i.e., who, when and
why anyone accessed their record for any reason).
The final rules have not yet been established, but it is advisable
for all practitioners to remain aware of these upcoming requirements and
be prepared to meet them before they are enforced. Theoretically, a “cer-
tified” EHR program takes these requirements and provisions into ac-
count, so if one purchases and implements these programs in their prac-
tice, many of these provisions will be able to be met. Unfortunately, for
any “early adopter” dentists who wish to implement a certified EHR pro-
gram for their practice, only one is available at this time. Several compa-
nies, although not certified currently, have indicated they were aware of
the situation and were planning eventually to introduce a certified pro-
gram. Again, it is advised that you keep up to date with your practice
management software company for updates or “modules” to meet these
requirements and insist they be provided if the software company is not
considering these issues.
There are some other implications of this push for EHR adoption
for dentistry. These include e-prescribing (submitting prescriptions digi-
tally online) ability and monitoring as well as the adoption of the Sys-
tematized Nomenclature of Dentistry (SNODENT), which was designed
by the American Dental Association for use in the electronic health and
dental records environment and essentially is a single accepted “diction-
ary” of dental terms in order to standardize/digitize everything “dental.”
There also is a requirement of diagnosis codes for payment (long
common in medicine, the ADA currently is updating claim forms to in-
clude up to four diagnosis codes since some large dental insurers are add-
ing diagnosis codes to claim requirements), as well as requirements by
16
Simmons
insurers and dental boards that all images, notes, models, letters and bill-
ing be provided in a standardized digital format.
It also is wise to remember some of the other intents of an EHR
according to the government are their supposed ability to “decrease
costs,” potentially due to their intended ability to monitor “quality meas-
ures” and adjust healthcare practices “appropriately” (through further
legislation, payment adjustments, fees). They also will provide for “life-
time” radiation exposure monitoring because certified EHRs will have
the capability of recording radiation exposure data and reporting it.
The reporting described above potentially could be a big issue
for those dentists taking or prescribing cone beam computed tomographs
(CBCTs) since the Federal Department of Agriculture (FDA, under
which the HHS resides), per their “Initiative to Reduce Unnecessary Ra-
diation Exposure from Medical Imaging” issued in February 2010, is
looking closely at CTs. This publication reports that approximately 89%
of the yearly exposure of the U.S. population is due to CTs, despite the
fact that CT scans account for only 26% of the total of all imaging pro-
cedures. Although “medical” imaging is used by the FDA in the title,
dentistry definitely is included; the first table in the FDA’s publication
specifically includes “dental x-ray.” Of particular interest to orthodon-
tists and pediatric dentists is the point the publication stresses concerning
the deleterious impact of ionizing radiation on younger individuals that is
greater than that for adults.
In that the government will be promoting and advertising the
EHR heavily in all provider settings, patients quickly will expect dental
offices to be EHR compliant as this becomes commonplace in the other
“healthcare” settings to which they are exposed. According to the ONC,
more than 21,000 providers had initiated registration for the EHR incen-
tive programs during the first month it was available (January, 2011) and
more than 45,000 additional providers had requested information or reg-
istration help from regional extension centers during this same time.
In addition, it quickly is becoming obvious that third party pay-
ers will require offices to interact with them in an EHR-compliant fash-
ion (because it will save them money and resources), due to potential
legal implications many malpractice/liability insurers may require their
clients to be EHR compliant, privacy/security regulations essentially will
require it (i.e., each office must have a “Privacy & Security Officer,” per
DHHS Guideline 45 CFR, Part 146), pharmacies/DEA likely will re-
17
Electronic Patient Records
quire, and lastly new (or updates to) imaging hardware/software will re-
quire DICOM compatibility.
FINAL REMARKS
Lastly, on a personal note, if and when one is contemplating
PHR options, it is useful to take into account the findings of a “Roundta-
ble on PHRs” the ONC conducted and published in their blog of Decem-
ber 3, 2010. At the PHR roundtable, four panels of experts and industry
representatives explored the growth of PHRs, focusing on the nature and
adequacy of privacy and security protections.
The key message from this roundtable was that PHRs grow in
value when people find them useful and 'trustworthy. Their usefulness
grows as they are able to pull information readily from EHRs and other
sources of clinical information, as well as from monitoring devices and
mobile applications. The usefulness increases even more as that informa-
tion can be organized to help people with their particular healthcare con-
cerns and inform clinical decision making.
18
SOCIAL MEDIA:
WHAT EVERY CLINICIAN SHOULD KNOW
Greg Jorgensen
ABSTRACT
Marketing has changed: interruptive marketing is out and inbound marketing is
in. The Internet has evolved from a brochure display rack to a Starbucks where
collaboration is the key. Social media is any web-based service that facilitates
interaction between users. Examples of social media include social networks,
blogging (publishing), microblogging, media sharing (photo, audio and video),
social bookmarketing, and product and professional reviews. New patients find
our offices via dentist referrals, referrals from their friends and through their
own research. Social media not only disseminates information about our prac-
tices, it also creates loyalty in our current patients that encourages them to refer
their friends. Although there are thousands of web-based services that qualify as
social media, there are some that are better suited to promoting dental practices
than others. Five social media services have been selected that will provide a
good starting point for dental practitioners, including: Twitter, YouTube, a prac-
tice blog, Facebook and Google Places. The pros, cons and uses of these sites
are discussed. Once the practice has set up its presence on social media sites, it
needs to develop a strategy for keeping it up to date and publicizing it to its pa-
tients.
KEY WORDS: social media, marketing, Internet, online, new patients
SOCIAL MEDIA DEFINED
The “New Internet”
Although the “consumer” Internet has been around since the
1980s, there has been a fundamental shift in the way that users perceive
and interact with it in the past six or seven years. Before 2004, the Inter-
net was essentially an electronic version of the brochure racks found in
the lobbies of hotels. Websites were simply static brochures that de-
scribed products and services — essentially ads for our businesses. Visi-
19
Social Media
tors could read only what the businesses wanted them to see. It was a
one-way street.
In the mid-2000s, the information technology world started talk-
ing about a “new Internet” dubbed “Web 2.0.” It was characterized by
web applications that facilitated collaboration between users. While the
old Internet (Web 1.02) limited users to viewing content that businesses
had posted themselves, Web 2.0 encouraged social interaction between
users and the creation of user-generated content. The development of
Web 2.0 brought with it a lexicon of new terms like social networks,
blogs, wikis and video sharing. If Web 1.0 was a brochure rack, today’s
web is more of a water cooler or a Starbucks where friends and col-
leagues meet to discuss ideas and products that are important to them.
Outbound vs. Inbound Marketing
Historically, we never have had to look for advertising – it found
us everywhere; on TV, the radio, in newspapers and magazines. Adver-
tisers interrupted whatever we were doing to present their products. Un-
fortunately, these advertisements could not focus on those most likely to
be interested, so a shotgun approach was applied. Consumers do not like
being interrupted as evidenced by the rise of Tivo and XM-Radio; they
are willing to pay for avoiding advertisements. Consequently, only 18%
of TV ad campaigns are profitable (Weber, 2007). And yet we all buy
products and want information when we need it. Enter “inbound marketing.”
Inbound marketing is a style of marketing that focuses on being
found by customers. Godin (1999) refers to this as permission marketing.
Scott (2010) suggests that with inbound marketing, businesses must now
“earn their way in,” whereas with outbound marketing, they used to have
to “buy, beg or bug their way in.” Businesses earn the trust of consumers
by publishing useful information on blogs, getting great reviews and then
benefiting from the recommendations of buyers’ friends. Seventy-eight
percent of consumers trust peer recommendations (http://blog.nielsen.
com/nielsenwire/consumer/global-advertising-consumers-trust-real-friends
-and-virtual-strangers-the-most/), while only 14% believe advertisers
(Weber, 2007). Social media is the vehicle for inbound marketing.
Social Media
Social media are web-based sites and services that facilitate in-
teraction between users. Kaplan and Haenlein (2010) add that this tech-
nology allows the creation and exchange of user-generated content. Na-
20
Jorgensen
tions (2011) defines media as an instrument of communication and social
media as communication on a two-way.
There are many forms of social media, but there is always one
common thread – collaboration between users. While there are no hard
and fast definitions about what constitutes social media, there are some
undisputed categories: social networks; publishing or blogging; photo
sharing; audio; Video; micro-blogging; Social bookmarking; product re-
Views; and business reviews.
Social Networks
A social network is a group of people who come together be-
cause they have something in common. They come together online and
their commonality could be anything: they may live in the same commu-
nity, work at the same company, have graduated from the same school or
be interested in the same hobbies. Although online social networks come
in many forms, they all share some common features. Perhaps the easiest
way to explain this is to look at the largest social network, Facebook.
The first common feature of almost any social media service is a
user profile. Users are required to share some information, but they typi-
cally have some say over what and how much is published on the site.
The information in this profile is where community members indicate
what they have in common (i.e., schools, hobbies) that allows others to
connect with them. Most social networks use some type of “friending”
protocol allowing users to select with whom they will interact. There are
many different ways that users collaborate on Facebook. The most com-
mon way is by posting your “status” (what you are doing, thinking or
feeling at any given moment) on your “wall.” Not only can you share
your thoughts, you also can share pictures, videos and links. When you
post something on your wall, it is spread over the social network for all
of your friends to see. The collaboration begins when they see your post
and “like it,” comment on it or pass it along to their friends.
The information, pictures or links appear on another page or fea-
ture of Facebook called a news feed. This is a constantly updated posting
of the things that your friends are thinking, doing or feeling. In addition
to posting things on your wall and news feed, users also can communi-
cate with each other using messages (much like email) or in real time
using a built-in chat feature. Additional features of this social network
are a calendar of events, photo albums and optional pages containing
documents or notes that you wish to share. Social networks are essen-
21
Social Media
tially a family or class reunion, a travel log, an event calendar and/or a
communication tool all combined into one.
Blogs
Blog is a social media vehicle derived from the phase “web log.”
It is an online log or journal about any topic the author wishes to share.
In years past, publishing original content for all to see required talent,
training and a contract. Today, anyone can create his/her own blog for
free with very little know-how required. Blogs began as a scrolling text
entry that looked like a journal. In recent years, however, the features of
blogging software have allowed blogs to look exactly like a regular web-
site; many of the websites you frequent today may be built on blogging
software which is undetectable as such. Hints that you are reading a blog
include:
1. It is updated constantly and may even have dates on
the posts and articles in chronological order;
2. There is a way to interact with the author via social
media links or comment boxes;
3. Archived articles which you can search for and ac-
cess; and/or
4. Some way to “subscribe” to the author’s “regulars”
posts.
Some of the most common blogging platforms include Blogger
(now owned by Google), Wordpress, Tumbler and Typepad. Each has its
own advantages. Some are easy to use while others are more customiza-
ble. Done right, you probably never will know which product the author
is using. Blogs are published on hundreds of thousands of topics that
share thoughts, information or instructions. One key feature mentioned
previously is the ability to subscribe to the author’s posts using email or
an RSS feed. RSS stands for “Really Simple Syndication.” The reason
RSS is so valuable is that instead of logging onto multiple websites or
blogs for new information, updates automatically come to you because
the software “pushes” the updates to your cell phone or computer. RSS
readers are programs that collect updates and present them in a readable,
standardized format.
Microblogs
A microblog is a small blog. The easiest way to think about it is
like a global text messaging system. The best example of this genre of
22
Jorgensen
social media is Twitter, which is a service that has only one way to share
information – a status update box. Each communication or “tweet” is
limited to 140 characters. The number 140 was selected because that is
the maximum number of characters that can be sent in a text messages on
a cell phone. Like most online social media services, users have friends
(or in the case of Twitter, “followers”) and each status update is posted
on the “feed” of those friends. Because the transmissible data is limited
to 140 characters, Twitter lends itself to short frequent updates. While
most websites or blogs are updated only monthly or weekly, Twitter
statuses usually are updated multiple times per day. p
Twitter quickly gained popularity by fans wanting to follow the
day-to-day activities of their favorite celebrities. For many, this is still
their primary use. Some big businesses have been able to harness the
power of Twitter to improve their customer service. Dell and Comcast,
for example, have social media specialists who do nothing but monitor
cyberspace for mentions of their brand. Tools like Tweetdeck and Hoot-
suite can be used to “listen” for a particular keyword being tweeted from
anywhere in the world. When a complaint about Comcast’s Internet or
cable service comes across the Twitter network, Comcast's social media
people are on top of it immediately. Besides customer Service, some
businesses use Twitter to announce events, post weather statuses, educate
their followers or share interesting links.
Media Sharing Sites
The category of social media sharing services includes sites that
share videos (YouTube), music (Pandora and iTunes), photos (Flickr and
Picasa) and presentations (Slideshare). At first glance it may not be obvi-
ous why these services are considered social media, but all require the
creation of user profiles and allow collaboration between users. You-
Tube, for example, allows viewers to rate videos and make comments. It
also facilitates the sharing of links to its content via other social media
services. The same holds true for Flickr, iTunes and Slideshare. The “so-
cial” aspects of these sites allow users to save time and find content more
quickly that is entertaining, useful and worthwhile.
Social Bookmarking
One interesting type of social media is social bookmarking.
While most Internet browsers have some way to allow you to save links
to pages previously visited, social bookmarking sites like Delicious take
bookmark management to a new level. Instead of just storing the link of
23
Social Media
an interesting site for you, Delicious allows you to tag or categorize your
link so that you can find it more easily later on. In addition, as with other
social media services, Delicious allows users to publish their bookmarks
in a central location so that their friends can share the links that they find
noteworthy.
Digg and Reddit not only share bookmarks, they promote the
sites that their users find most interesting and important. Readers “vote”
on pages, posts and sites and leave comments, providing the Social ele-
ment found in all social media services.
Product and Service Reviews
Seventy-eight percent of consumers trust peers more than adver-
tisers (http://blog.nielsen.com/nielsenwiré/consumer/global-advertising-
consumers-trust-real-friends-and-virtual-strangers-the-most/). That inher-
ent trust in our friends is the foundation for sites that rate products and
Services. Most of us think of amazon.com as an online shopping mall.
Besides having a huge inventory of everything imaginable, usually avail-
able the next day via FedEx, the social media component of amazon.com
can be a useful tool as we try and determine which of the available prod-
ucts will meet our needs. It is not uncommon to log onto amazon.com to
buy a particular product only to find that others also have not had a good
experience.
Not only are there social media sites like Amazon and Epinions
that rate products, there also are a growing number of sites that rate serv-
ices including UrbanSpoon and Yelp (restaurants), Travel Advisor (ho-
tels and restaurants) and Angie’s list (contractors and handymen). On the
rise are rating sites for doctors and other professionals. Sites that rate
dentists and orthodontists include Dr. Oogle, HealthGrades, Angie’s List
and Google Places.
THE RELATIONSHIP BETWEEN SOCIAL MEDIA
AND NEW PATIENTS
Dentist Referrals
In order to understand how social media can help lead patients to
our offices, an overview of how new patients end up in our chairs is war-
ranted. The most “old-fashioned” source of patients is a referral from the
patient’s general dentist who typically sees his patients a couple of times
each year and is usually the first professional to recognize the need for
braces. Although the percentage of patients that come to our practices via
24
Jorgensen
dentist referrals fluctuates, these referrals are responsible for a significant
number of our patients.
Patient Referrals
Although patients usually do not diagnose malocclusions in their
friends’ mouths, they do discuss their experiences in our offices. When a
patient is informed that s/he needs braces, the dentist often makes a refer-
ral to a specific orthodontist. While some patients call and schedule with
this recommended doctor, others just hear that their child needs braces
and go immediately to their friends for information about “their’ ortho-
dontist.
Self-Referral
More patients now are researching and selecting doctors on their
own by searching the Internet. While they may become familiar with a
name through referrals, advertising, sponsorships or community in-
volvement, their ultimate choice is influenced heavily by what they dis-
cover online. Practice and professional organization websites contain
information to help evaluate a doctor’s training and qualifications.
The Role of Social Media
Social media efforts most commonly are directed at our own pa-
tients and the “self-referrers” just described. Consistent social interaction
helps keep our current patients connected (loyal) to the practice and en-
courages them to refer their families and friends. They also can perform
a valuable service for future patients by sharing their experience with our
offices via reviews and testimonials. Social media also helps potential
patients find our offices on their own and learn more about us.
WHICH SOCIAL MEDIA SERVICES ARE MOST
RELEVANT TO OUR PRACTICES.”
Main Practice Website
Regardless of how they find it, the ultimate goal of our social
media effort is to direct new patients to our main practice website, pro-
vide information about our services and get them to schedule initial con-
Sultations. The practice website is the hub of all online activities. It can
be effective only if patients can find it.
The most impersonal way for patients to find our website is
through a search engine like Google or Bing. Those who search for
25
Social Media
words like braces, orthodontist and Invisalign are the same people who
used to look at ads in the Yellow Pages to help them select their doctor.
Whether or not you desire patients who find you on their own (many
times price shoppers looking for the “best deal”), it is important that all
patients be able to find your website. Indeed patients who are referred to
us via their friends or dentist more readily accept treatment than those
who find us on their own. Consumers value an endorsement from a
friend on Facebook much more than merely accepting the result of Goo-
gle search. For this reason, we would be wise to incorporate social media
into our overall practice-building strategy.
Hundreds of sites now qualify as part of the social media land-
scape. The following are suggested as those that will give your practice
the most “bang for the buck.” •
#5 Twitter
Twitter is a micro-blogging service that can be thought of as a
global text-messaging system for your practice. While your text mes-
sages or “tweets” are broadcast to the entire Twitter network, only those
who have chosen to “follow” you actually will see them.
A Twitter account is free, easy to set up and easy to maintain.
Getting registered takes less than five minutes and requires the least
amount of setup of any social media site. Unlike other services that re-
quire elaborate homepages, photo uploads and the entry of a lot of in-
formation about you and your business, Twitter limits you to a 160-
character profile, a profile picture and an online name. After your ac-
count is set up, content needs to be created. Twitter can be used to notify
patients of upcoming events, recent website/blog updates, weather up-
dates or if your schedule is running on time.
Twitter has been included in my list for two reasons. First, it can
benefit your practice by improving communication with your current
patients. Second, it increases your credibility with Google. Google search
algorithms are designed to discern the authority or validity of sources so
that users receive the most accurate results in their search. Although
those algorithms change constantly, it is believed that a website associ-
ated with 2,000 followers is a more credible source than a site with only
20 or 30 followers. Theoretically, a person followed by more people
must be more authoritative!
Unlike other social media services to be described, Twitter re-
quires frequent updates or “tweets.” This might be an assignment that
26
Jorgensen
you can delegate to a staff member. The most difficult part of getting the
Twitter ball rolling is getting followers; this is a challenge facing all so-
cial media campaigns and will be discussed later.
Twitter’s greatest weakness is that if your patients or prospective
patients are not using Twitter actively, they will never see your messages
and your efforts will be wasted completely. It is estimated that less than
7% of our online patients actually use Twitter (Webster, 2010). Twitter
should be an adjunct only to support a much larger Social media campaign.
#4 YouTube
YouTube is the number one video-sharing site on the Internet. Its
integrated search engine is second only to Google in the number of
searches performed daily.
Creating a practice YouTube channel can serve as a hub for dis-
seminating video information to your patients. Links to videos on your
YouTube channel can be placed on your main website, into emails and
electronic newsletters, into Facebook posts and Twitter tweets, as well as
on blogs. Allowing YouTube to host your videos keeps your site running
faster and points those who find your content on YouTube back to your site.
Examples of videos that can be posted on YouTube include prac-
tice information videos, how-to videos (i.e., brushing), videos about pa-
tients and patient events (i.e., patient appreciation parties).
With video cameras built in to most cell phones and still cam-
eras, capturing video is not difficult. Dedicated video cameras (like the
Flip) cost less than $200 and give great results. Although this is easy to
do, making, editing and posting videos takes time. Like Twitter, creation
and posting of practice videos on your YouTube site might best be dele-
gated to a staff member or part-time employee with some video-making
experience.
#3 A Blog
A blog is an online collection of chronological articles dealing
with every topic imaginable. Blogs have become much more sophisti-
cated in recent years such that recognizing the difference between a blog
and a website is difficult. Practice blogs can contain information about
the doctor, the staff, practice policies, practice philosophies, new tech-
niques, new products, events or anything else that your patients or poten-
tial patients may find interesting.
27
Social Media
Starting a blog is included as the #3 best implementation of so-
cial media because Google regards blog entries as new content; each
blog entry is a new page on your website. Unlike the static pages of your
main website, your blog changes every time you add a post. Google no-
tices the new content and deems your site as more up-to-date and rele-
vant than competitors whose site remains unchanged week after week.
Another benefit is that the content of each blog post is searchable by In-
ternet search engines. Both of these advantages are directly linked to
Search Engine Optimization (SEO; which is an entirely different topic
altogether). If a patient is looking for information on how to adapt a
mouth guard to be worn with braces and finds your site, he may regard
you as an “in the know” orthodontist and contact you for additional in-
formation or possibly an appointment.
Although integrating a blog into your website will require some
work on the part of your IT people, most blogging software is free. Some
orthodontic website companies can even be paid to update your blog on a
regular basis. The benefit of writing your own blog is that you know the
issues that are most important to your patients and can address them for-
mally online. This allows doctors and staff members to refer patients to
the website for answers to common questions like, “Why doesn’t your
practice take Medicaid?” or “How old should my son be before I bring
him in to see you? The ability to “park” thorough answers to frequently
asked questions online can be a huge time savings and get more people
to check out your webpage.
#2 Facebook
Facebook is the largest social network in the world today. People
currently spend more time on Facebook than they do searching Google
or looking at porn (the former #1 use of time on the Internet). As dis-
cussed earlier, Facebook is an online community of friends, relatives,
coworkers, classmates and even patients who come together to keep
track of what is going on and make new acquaintances.
Facebook is included as an important social media resource for
your practice because two-thirds of your patients and their parents are
already on it. It is free, easy to use and it can be fun and interesting. Up-
dates arrive on your patients’ news feeds without them having to navi-
gate to your website. Facebook fans are those who have chosen to re-
ceive your updates and not just random people getting hit by a shotgun
approach. Facebook updates can include information about current practice
28
Jorgensen
events, new products and services, information about the doctor and
staff, and interesting things about your patients and their activities. You
can highlight honors and awards the doctor or his patients receive. You
can notify patients about new articles on your blog. You can post pic-
tures and videos that might be of interest to your fans. Facebook is perti-
nent because it is where your patients are “hanging out.”
To get started with a Facebook fan page, you first need a per-
sonal page. If you do not have one of these yet, ask your staff how to get
one; I guarantee they know how. Once you have a personal profile, you
can create a fan page. If you feel overwhelmed by the idea of setting up
your own, there are many companies and consultants who can help you
with this task. Additionally, the AAO has an article on its website that
provides a step-by-step guide on how to do it yourself.
#1 Google Places Page
It might surprise you that a Google Places page is noted as the #1
Social media site needing your attention right now. A Google Places page
link appears on Google next to your name when someone performs a
search for your business and is created for you automatically with or
without your authorization.
Google Places allows business owners to edit the content of their
existing listing or to add a new listing to Google’s local database. By
ensuring that basic information is up-to-date and providing additional
details (i.e., photos, hours and coupons), business owners can stand out
on the map to attract more customers.
Google Places Pages help users find the best sources for infor-
mation across the entire web, including business-listing details, reviews,
photos and nearby public transit. There are Places pages for a broad
range of “places,” including places like a business, park, point of interest,
transit stop or an entire city. Google Places has become the online “Yel-
low Pages.”
A Google Places page has basic phonebook information like
name, address and phone number as well as a contact email. Addition-
ally, there is an automatic map showing where you are located, a picture
of the business (from Google Earth), driving directions, information
about hours and parking, and even a link to mass transportation in your
area. Although there is a link to your website, your Places Page already
contains much of the information found there including your logo, de-
scription of your business, profile statement, the brands you carry (i.e.,
29
Social Media
Damon or Invisalign), the forms of payment you accept, along with pho-
tos and videos of your practice.
What qualifies your Google Places page for a social media serv-
ice, however, is the presence of reviews. These reviews are not only
those entered directly into Google, they are consolidated from other In-
ternet sites such as Yahoo, Yelp, Dr. Oogle and HealthGrades.com. You
have no control over these reviews (unless they are flagged as inappro-
priate) and they may be helpful or damaging depending upon what they
say. Reviews are critical to how your business is seen by the Google
search engine.
The most important thing to getting your Places Page to show up
on the first page of Google’s search results is “claiming” your site. You
most likely will not have to create your own Places Page, however. You
can find it most easily by typing your name and your zip code into the
Google Search box. Once there, you will see “Edit This Place” or “Busi-
ness Owner,” either will get you one level deeper where you will be able
to claim the business. Google will verify that you truly are the owner
with an automated phone call to your business. You will need to verify
your business at work since you will be given a PIN code by the phone
service that you will need to enter into a dialogue box on your computer.
Once you have claimed that you are, in fact, your business, you can edit
and enhance the information that appears.
WHERE TO FROM HERE!
Develop a Social Media Strategy
Put down in writing how you are going to incorporate social me-
dia into your practice’s overall marketing plan. Have your main website
updated to facilitate a social media campaign and make sure your Google
Places Page is accurate. Set up each social media service right away and
get started. Make goals for frequency of updates and who will perform
them. Your YouTube site should be updated monthly. Your blog and
Facebook fan page should be updated weekly (more than that can get
annoying and people may “unlike” you). You also should have someone
monitor the reviews showing up on Google Places on a weekly basis.
Most Twitterers expect daily updates.
Start Creating Content
Everything does not need to be perfect before you get started; get
started today. You can claim your Google Place page tonight and can
30
Jorgensen
create a Facebook profile along with a fan page for your practice in about
an hour. Opening a Twitter account will take you less than three minutes.
Just think, you could be tweeting before you go to bed tonight. Find
those in your practice who already are familiar with social media and
delegate some of the responsibility for content. Hire patients to help you
make Videos and take pictures for your site; they already do that for their
own sites. Make it your goal to give your patients and potential patients
value for Visiting your sites.
Get the Word Out
Once you have content for your patients to enjoy, let them know.
Incorporate social media icons into your website, blog, letters, emails
and other forms of advertising. Use one form of social media to promote
your other sites (i.e., announce your newest blog post on Facebook and
Twitter). Have contests that encourage Facebook “likes” and Twitter
“follows.” Print up cheap business cards that contain the links to your
sites. Place a kiosk computer at your front desk or rig an iPad so that par-
ents can “like,” “follow” or review you while they are still at your office.
CONCLUSION
Social media will affect how we do business regardless of
whether or not we choose to participate. Patients talk about us and al-
ways have. Now they have a much more efficient way of doing so.
Most importantly, no matter how excited you get about social
media, realize that making friends online takes time just like making
friends in the real world. You have to be in it for the long haul and may
not see measurable results for some time. The long-term result, however,
will be that you will become part of the online discussion; ultimately,
this will translate into more patients for you and your practice.
REFERENCES
Godin S. Permission Marketing: Turning Strangers Into Friends, and
Friends Into Customers. New York, NY: Simon & Schuster 1999.
Kaplan AM, Haenlein M. Users of the world, unite! The challenges and
opportunities of social media. Business Horizons 2010:53:59-68.
Nations D. "What is Social Media?” http://webtrends.about.com/
od/web.20/a/social-media.htm. (C) 2011.
Scott DM. The New Rules of Marketing and PR: How to Use Social Me-
dia. Blogs, News Releases, Online Video, and Viral Marketing to
31
Social Media
Reach Buyers Directly. 2nd ed. Hoboken, NJ: John Wiley & Sons
Inc., 2010.
Weber L. Marketing to the Social Web: How Digital Customer Commu-
nities Build Your Business. 1st ed. Hoboken, NJ: John Wiley & Sons
Inc., 2007.
Webster T. “Twitter Usage in America.” http://www.edisonresearch.
com/home/archives/2010/04/twitter usage_in_america_2010_1.php
(April 29, 2010).
32
CONNECTING THE DOTS:
ARE YOU UP TO SPEED INTEGRATING YOUR
INTERNET MARKETING PLAN2
Mary Kay Miller
ABSTRACT
Success in any business environment today requires grabbing the attention of the
most entrepreneurial and tech-friendly generations in history. They also are the
most overstressed and distracted demographics to date. Failing to understand
and develop marketing strategies that appeal to your patient market and their
personal preferences – both in learning and information gathering – may be a
deterrent to practice growth and success. It is my opinion that most orthodontists
and their teams have minimal knowledge and training when it comes to
designing and implementing an Internet marketing program to attract new
patients and build their business for the future. This chapter reviews some of the
general concepts required to create an effective Internet marketing plan along
with an explanation of how the search engines such as Google-, Yahoo- and
Bing-organized and index websites and social media in local search.
KEY WORDS: Internet marketing, search engine optimization (SEO), website
design, local search, mobile marketing
The landscape on the Internet is changing at lightning speed. It is
important that orthodontists and their marketing team understand how
the Internet works to maintain or advance their competitive edge with an
integrated marketing plan that reaches targeted consumers of all ages.
The Internet affords you the opportunity to promote all your per-
Sonal public relations marketing messages quickly, full-time, inexpen-
sively and with the least amount of effort. While each marketing strategy
works as a stand-alone program in your practice, integration of your cur-
rent internal and external programs under one umbrella of exposure is
much more effective to promote your business. This approach is no dif-
ferent than integrating an effective practice management software pack-
33
Internet Marketing Plan
age to streamline the day-to-day operations of your practice and treat-
ment delivery.
Due to the explosion of mobile technology, information gather-
ing on cell phones and the introduction of the iPad, we must consider all
factors and determine its affect on your current marketing programs for
maximum results. Historians already are predicting that Smartphones and
the iPad will revolutionize how consumers use the Internet in the future —
and it is only just beginning.
The Internet still is in its infancy and the learning curve is over-
whelming, to say the least. Advances in digital technology are moving at
warp speed and updates are nonstop. To make it even more challenging,
many business owners and their staff are unfamiliar with how all the
pieces of an integrated internet marketing puzzle work together correctly
– a program that includes their website, social media, offline internal and
external marketing strategies and now mobile marketing.
Exploring this new world of marketing is an eye opener. The In-
ternet is the rocket fuel that can help your business take off, but it is YOU
who must set it in motion. Understanding how all the different pieces of
the Internet marketing puzzle work together is key to your online success.
INTERNET MARKETING DO OR DIE WITH SEARCH ENGINE
OPTIMIZATION (SEO)
Five pieces of the Internet marketing puzzle include:
1. SEO: The first and most importance piece of the puz-
zle for online exposure;
Attract new patients to your website;
Engage them with your marketing message;
Call to action to schedule an appointment; and
5. Track results for return on investment (ROI).
What Is SEO2
Search Engine Optimization (SEO) is “the science and art” of
achieving higher visibility on the search engines. In September 2010 in
the U.S., Google handled 66% of search queries followed by Yahoo with
17%, according to ComScore, a company that measures the digital
world. In March 2011, Google reportedly handled 97% of mobile search
UISCTS.
;
34
Miller
Google dictates the rules of engagement when it comes to Inter-
net visibility and page ranking. Google is the dominant search engine and
can be considered “King of the Internet.” SEO rules are based on mathe-
matical algorithms programmed to index keyword text and HTML cod-
ing in:
• WebSites
• Blogs
• Press releases/articles
• Social networking sites (e.g., Facebook and Twitter)
• YouTube and Videos p
Why Is SEO Important?
• It improves the number of visitors who can find and
choose your website or social media on the search
engines in your local area to increase new patient re-
ferrals to build your business.
• It improves natural or “organic” search engine results
in page ranking.
• It interacts with local business listings in Google
Places, Yahoo and Bing.
• It levels the competitive playing field for orthodon-
tists, dentists and pediatric dentists.
Your website and social networking sites are one among mil-
lions. The greater the number of competitors, the harder it is to appear on
page one in local areas, especially in a major metropolitan demographic.
SEO will make or break your Internet presence.
Search engine spiders or “Google bots” are programmed to read
the mathematical algorithm only. These Google bots:
• Cannot understand your written content;
* Do not care what your website looks like;
• Can not see photos or watch video; and/or
* Do not care about quality customer service, treatment
delivery or experience level. -
If you do not follow their rules, you might as well be invisible in
the eyes of today’s tech savvy consumers researching online for ortho-
dontic treatment providers in your area during all hours of the day and
night.
35
Internet Marketing Plan
What Are Search Engines Programmed to Notice or Index in the Algo-
rithm?
The algorithms used to rank your website, in relationship to your
competitors and similar websites across the country by each search en-
gine, are a blend of over 50 different variables. They include search en-
gine data, website structure, approximate traffic click-through rate, site
performance and other factors that are kept secret to deter spammers.
Your business can have an outstanding page rank, but still be invisible to
consumers in search, if the meta tag coding of your website is incorrect
for major “consumer” keywords used in local search. Meta tags are little
lines of code that are placed between the ‘HEAD- and the 3/HEAD-
tags in your site's HTML code. They are designed to give search engines
instructions on what your page is about and how they should treat it.
These tags are not displayed to humans visiting your site, but they can be
used to influence the way your site appears in the search results.
Top major consumer keywords are orthodontist, Invisalign,
braces, orthodontics + locations and zip codes. Minor consumer key-
words are invisible braces, cost of braces, clear braces, adult orthodontics
and early treatment orthodontics.
Most Important Algorithm Variables in Order of Importance
1. Domain name: When choosing a domain name, use
major consumer keywords and location vs. branded
practice name for best results (e.g., Houstonorthodon-
tist.com or Houstonbraces.com).
2. Meta tags are based on keywords “consumers” use
when searching for an orthodontist. They are added
to source coding in your website by your webmaster.
They allow the website owner the ability to some-
what control how your web pages are described to the
search engines.
* Title tag: Defines your business and location to
the search engines. The title tag is the text dis-
played in the very top bar of an Internet
browser or above the description tag in search
results (Figs. 1-2).
36
Miller
COrthodontist. Braces. nºsauga. in Anoka, MN. Champiºn, Elk River - Windows internet Explorer
ºº - ºr wowºcom
Figure 1. Title meta tag of an orthodontic website. The title tag should
be added by your webmaster when the site is created based on most
commonly used orthodontic keywords in local search.
Orthodontist, Braces, Invisalign. In Anoka, MN, Champlin, Elk River
Orthodontist Dr. Bruce Dormanen of WOW Orthodontics in Anoka, Champlin, Elk River,
Princeton, MN offers invisalign, braces, and outstanding customer...
www.wowortho.com/- Cached - Similar- º
Figure 2. A “snippet” of information a consumer finds on search results
after typing in keywords “orthodontist Anoka MN.” It contains the “ti-
tle meta tag” and “description meta tag” of the practice added by the
webmaster to attract new patients in local search engine results. Google
stopped reading “keyword tags” in their algorithm years ago as a deter-
rent to spamming.
-
3. Back links (incoming links to a website or web page)
to your site from outside sources: Proof to search en-
gines that people are interested in your website.
4. Click through rate or number of visitors to your
website: Bolstered by patient login services, patient
rewards programs, Internet contests and social media
drive current patients to your website to increase traf-
fic and improve or maintain page ranking.
5. Written text on page: Consumer and local keywords
should be added to written text on home page in first
few sentences and sprinkled throughout page.
6. Longevity of the site: If changing domain name or
designing a new website, 301 redirect is critical to
maintain history. Practices just entering the game
with their first website will find it difficult to rank in
competitive areas, especially a start-up practice.
7. Alt tags on photograph: Keyword code photographs
so search engines know what they are about for re-
lated content to optimize site.

37
Internet Marketing Plan
Meta tags and coding can be updated to improve page ranking of
an existing site without complete site redesign. The algorithm is chang-
ing all the time; it is your responsibility to keep up with the latest up-
dates. Most updates do not affect meta tag coding once set up correctly
for local search.
Avoid the use of flash websites or flash headers with artwork to
display contact information on your website. Flash is a multimedia
platform used to add animation, Video and interactivity to web pages.
Flash is used frequently for advertisements, games and flash animations
for broadcast. In an orthodontic context, flash items includes practice
name, doctor’s name(s), address(es) and phone number(s). Search en-
gines are programmed to read text, not photographs. Have you ever tried
to copy and paste content off the Internet and you could not highlight it
with your mouse? This problem occurs because the content was created
using Flash. Flash content also is not compatible with iPads and many
Smartphones. Flash uses photographs; HTML uses text. Remember,
Google bots cannot see photographs.
2010 GOOGLE UPDATES IN ALGORITHM: HOW IT
AFFECTS ORTHODONTIC WEBSITES AND BLOGS
June 2010: Speed of your site download time (measured in milliseconds)
affects page ranking in relationship to competitors. Design concepts to
avoid that slow down speed:
• Flash sites and moving flash headers.
• Photographs sized incorrectly for web use.
• Poor website architecture: Use a reputable webmas-
ter. Search engines favor WordPress format, an open
source blog tool and publishing platform that is de-
signed for speed, setup and easy editing.
• Video hosted on same server as website. Use You-
Tube, Amazon Video storage or ask webmaster to
host on separate server from website.
June 2010: Back links vs. traffic:
• Backlinks are incoming links to a website or web
page; traffic is the load on a communications device
or system. One of the principal jobs of a system ad-
ministrator is to monitor traffic levels and take ap-
propriate actions when traffic becomes heavy.
38
Miller
• Traffic to the site should be congruent with the num-
ber of back links added to the site as proof of relevant
COntent.
• This update was added to level the playing field for
businesses using SEO Specialists adding back links to
sites without increasing traffic accordingly.
October 15, 2010: Google local places update (maps area) and still ongo-
ing today:
* Google Places or the Maps area was reformatted
completely to accommodate easy access for consum-
ers using smart phones and iPad with mobile search.
• The SEO coding of your website is integrated in
many areas with your maps listings. This integration
will affect page one ranking in populated areas.
• Correct SEO setup of your website, verification of
maps listings and the number of reviews posted in the
maps area affects your overall page ranking.
A website alone no longer is enough to maintain or increase
page ranking in major metropolitan areas and towns with multiple com-
petitors. Social media sites that link directly to your website and each
other increase traffic to your site and create back links to improve or-
ganic page ranking on Search engine results page.
DETERMINE INTERNET MARKETING GOALS BEFORE
IMPLEMENTING SOCIAL MEDIA MARKETING
Doyle (2011) provided detailed research and insights on manag-
ing the evolving search and social climate for optimum results. This re-
port is distributed by Marketing Sherpa (www.marketingsherpa.com), a
resource that publishes useful news, case studies and best practices data
about Internet and integrated marketing. This company has monitored the
search marketing landscape yearly for the past seven years.
Results of Study
Search engine marketing has changed dramatically in the past
year and much more so than previous years. Sixty percent of businesses
surveyed report they are including SEO and social media in their market-
ing plans.
39
Internet Marketing Plan
More marketers reported SEO, rather than social media, as a
“very effective” way to:
• Increase brand or product awareness;
• Increase website traffic;
• Increase lead generation (new patients); and/or
• Increase offline sales revenue or production.
On the flipside, more marketers said social media was a “very ef-
fective” way to:
• Improve branding or reputation; or
• Improve public relations.
SEO marketing strategies are more effective at attracting atten-
tion of consumers to a business. However, social media is more likely to
increase positive thinking around a product, service and brand name.
Understanding Consumer Search Habits
* 40% of all search queries contain a city, state or zip
code (as of January 2011).
• 3 BILLION local searches every month.
• 82% researching online, follow up with offline local
action.
• 61% eventually made local purchases.
• Local search is used more often than both online and
offline Yellow Pages (think twice before contracting
yellow page, dexknows.com and superpages.com
services).
* Local maps listing on page one grabs attention first.
Consumers seldom venture to the second page in
maps or organic page ranking.
• Consumers click on the maps listings with most re-
views, both positive and negative.
• The higher your page rank, the more “consumers”
will click on your website. Forty percent of consum-
ers searching online click on the #1 website found in
organic page ranking.
• Above the fold in first three “organic” is considered
“prime Internet real estate.”
• In 2008, statistics report only 30% of consumers
would click on paid advertising. In 2010, it has
40
Miller
dropped significantly to only less than 5%. If you al-
ready are listed in the maps area and have a good
page rank, you might be smarter shifting online paid
advertising dollars to different areas of your market-
ing plan for better return on investment. Tracking ac-
curate results is critical when determining success.
--- - Invisaliºn - Trust lence.
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* Invisalign Right for You? Free consultation ORIGINAL VER SION
*37 W North Ave, chicagº, IL-1312,554-2100-piectiºns
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suite 800, 539 WNorth Avenue, chicagº-1 (312,542-3370-Directiºns
- Paid Advertising
incoln Park Dentist Dr.Sooº.com
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2554 N. cis-street-suite too, chicago me, 327-0014-piections
Places for orthodontist near chicago.il.
º Shobel Dentistry-chicago Dental office --- tº Google reviews
www.strobeldentistry.com-25E washingtonStreet, suite 1917, Chicago-(312)728–3135
º Pentalwoºs at seats. Dº Itasaºis & Associates -º- 12 Google reviews
www.dentalworks.com-2 North Statest, Chicago-(312) 20:1-1610
º Spector Howard Epps-- Place page
w-smilesandbraces.com -30 N. Michigan Ave+1812, Chicago-tºtz,726–9528
Find Chicago Dºctor
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º MG Dentistry - -2 Google reviews - - -
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*dentalmedicinechicago.info-30 North Michigan Avenue #1329, Chicago-tº 12)782-2844 offices Maº - Dentistry Appi.
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---------- --
Figure 3. Illustration of page one search listing for keywords “orthodontist Chi-
cago.” The highlighted yellow area is paid advertising. The area A-G with red
balloons is local maps listings with reviews that correspond to balloons on the
map. A-G listings are based on location rather than SEO shown in Figure 4. The
green area is the “organic” or “natural” search engine results pages a search en-
gine returns for a given search query.

41
Internet Marketing Plan
- Tucson Orthodontist Braces. For adults. Kids & Teens
-º-º-º-º-º-º:
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schedule Your Appointment Today.
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orthodontist Iucson Azºraces Tucsonlinvisalign Tucson-
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Orthofºros F.C. in Tucson, A2 (Arizona)-Orthodontists. Drs. Grob, Donovan, and K-car
offer affordable orthodontic treatment with braces and Invisalign
-on-º-º-º-o-o-º-n --G----on-ºn-on-on-
1751 West Orange Grove Road #111, Tucson
(520)257-1849
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www.drawinau-Cached
Tucson & Crovalley Orthodontists, offering Awide Selection of clear Braces
Specializing in Invisalign, Damon & Lingual Braces. For children, Teens & Adults
Contact Us-Appointments-Fractice Events-Before & After
º 5747 East 5th street. Tucson -(520)745-0554
"this place is great best-orthodontistintucson"-yellowpages.com (3)
yahoo.com (1)
Iucson Orthodontics. Braces Tucson Az. Orthodontist-
www.supersmitz.com/-Cached
Tucson A-Orthodontists. Dr Pearcy & Dr Raksanaves provide Braces, invisalign, and
other orthodontic treatment to adults and children. 520-742-1232.
1320 west In-Road. Tucson
º (520)742-1232
Leber Orthodontics. Orthodontist Tucson AZ. Braces -
------------
Leber orthodontics, a family tradition located intucson, Arizona. Cutting edge
technology for your braces and your smile including digital x-rays, Invisalign, ...
1647 navernonway+2. Tucson
520) 735-2323
doctoroogle.com (1)
cialist-T in SierraVista AZArizona-Andrew. -
www.braces by drºew.com/-Cached
Andrew Rosen Orthodontics is your Tucson, Sierra Vista, and Green Valley, AZ (Arizona)
orthodontic practice offering braces for children, teens, and adults.
1855. North Kolb Road. Tucson
(520) 290-0500
insiderpages.com (1)-doctoroogle.com (1)
Dr. Don Braces-Orthodontist Providing P lized Orthodontic-
------------------
Dr. Don Braces is located in Tucson, Arizona. Our priority is to provide the highest quality
personalized orthodontic care for you in a friendly and comfortable.
50.27 East Grant Road. Tucson
5201885-0344
Day John woos -
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Tucson, azeºtº-4505. what exactly is orthodontics? Is Dr. Day a good orthodontist?
is orthodontics really expensive? Is Orthodontics only for teenagers?
720 North Country Club Road. Tucson
(5201325–5658
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access to search Engines alonce
Place page
se-ºut-----
In 2011, Google added a second version of
search query which combines both maps
and "organic" listing for #1 - 7 page rank.
I I
º
As Google continues to update their
algorithm for local search moving
forward, it is still undetermined whether
figure 3, figure 4, or both will be found in
local search query in the future.
This illustrates why SEO is so important to
the visibility of your website. Websites
relying solely on maps listing and not SEO
risk losing their Internet exposure with
most popular consumer keywords.
























Miller
*— Figure 4. Illustration of page one, search listings for keywords “orthodontist
Tucson.” In many areas of the country, a new version of search query is found
with latest algorithm updates in 2011. Paid advertising area in yellow remains
the same; however, the maps area and “organic” search area is combined and
page ranking is determined by SEO rather than location. Websites ranked 8-11
are found below the maps area in green area rather than 1-10. There is no rhyme
or reason why Google displays one version vs. another and results can vary from
one day or week to the next.
Test Your Website for Success
You do not know what you do not know until you know it!
Before you determine the best course of action when creating an
effective Internet marketing program that integrates all the different
pieces of Internet marketing synergistically, you first must know how
your website ranks on the search engines for all major orthodontic key-
words in your local area. Your website is the “hub” of your Internet mar-
keting presence. If your website is not found in at least one of the top
three positions in “organic” page ranking in local search, you are losing
new patients to your competitors and a wealth of opportunity to build
your practice.
* Go to www.orthopreneur.com for access to a free
training video and tracking spreadsheet to determine
how your website is ranking on Google in local
search.
• Enter your name and email address in the designated
area on the homepage to receive a link to watch the
training video.
• Follow the instructions to test the visibility of your
website. Then repeat again for social media sites,
such as your blog, videos on YouTube and Facebook.
Are your sites found easily using local search key-
words?
* The ultimate goal is domination or multiple listings of
your practice on page one with your website and so-
cial media. This is not possible in major competitive
areas, but realistic in many suburban and outlying lo-
cations.
43
Internet Marketing Plan
Social Media Marketing to Improve SEO and Organic Page Ranking of
Your Website
Blogging is the most powerful SEO marketing tool available to-
day to promote your business and all forms of social media:
• It allows you to drive current patients to your website
and other forms of social media.
* Plug-ins integrate blogs with social media to auto-
matically post to Facebook, Twitter and RSS feeds,
all in one step.
• Blogging creates back links to your website and other
social media sites. When set up and optimized cor-
rectly, it will rank on page, one in local search in
many areas and sometimes outperform your website.
• A WordPress blog can be setup to look exactly like a
website with an integrated blog setup, eliminating the
need for a separate website, a tactic recommended for
first time website users. A WordPress blog format has
the ability to out-perform websites on the search en-
gines and your staff has complete back-end access to
edit all pages of the website. They easily can edit text,
add photos, upload video and add new pages to the
website without contacting your webmaster. Training
is minimal, format is similar to Microsoft Word and it
does not require a background in HTML or CSS for
website design once the site is created.
ePress releases promote practice products and services as well
as community efforts. Such releases increase traffic to website, create
back links when set up and optimized correctly and have the ability to
rank on page one in Some local areas.
Online articles highlight knowledge and treatment expertise in
the field of orthodontics. They increase traffic to website, create back
links when set up and optimized correctly and have the ability to rank on
page one in smaller local areas. Paid releases are recommended vs. free
releases.
YouTube and Video. Video is the preferred form of communica-
tion by consumers today. It is easy and inexpensive to create yourself, or
it can be outsourced to professionals. When set up and optimized cor-
rectly, video can be found on page one in local search. It drives consum-
ers to your website for more information and directs them to contact your
44
Miller
office for a new patient exam. Once created, it indefinitely offers 24/7
availability.
Facebook is not a suggested form of Internet marketing if your
main goal is to improve SEO or page ranking of website for visibility. It
is, however, a great social media platform with which to brand your prac-
tice and communicate with current patient base to build personal rela-
tionships between appointments. To be found in local search, the user-
name must be optimized correctly during setup and the fan base must
return frequently and socialize on the site. It is difficult to achieve page
one ranking on search in competitive areas. p
Forrester Research (www.forrester.com) is a technology and
market research company that provides pragmatic advice to global lead-
ers in business and technology. In the latest report by Forrester, social
networking is rated #10 out of 10 recommended online marketing tactics
to build a business.
Twitter is not a suggested form of Internet marketing if your
main goal is to attract new patients. In this author’s opinion, Twitter is
low on the list of social networking platforms and targets too small a
percentage of patients to be of value.
WHAT WORKED YESTERIDAY MAY NOT WORK TODAY
... AND WHAT WORKED TODAY
MAY NOT WORK TOMORROW
Reputation, treatment modalities and customer service are no
longer the only important factors for a thriving business. Savvy market-
ers of any age and experience level understand the Internet is an integral
part of the marketing mix when presenting a practice to today’s con-
sumer. The “perceived value of treatment and return on investment” in
the eyes of the public is the heart of any marketing program today. There
is no better vehicle to communicate your marketing message and to build
trust than an SEO online marketing strategy.
That being said, the foundation of any marketing program is that
good customer service and treatment delivery has been, and always will
be, the foundation of any successful marketing program, no matter what
the marketing medium.
If your foundation is weak, all the latest and greatest marketing
tools available are not going to make up for the lack of key business ele-
ments. The Internet and word of mouth referrals are the preferred form of
45
Internet Marketing Plan
communication among friends, family and professionals today. With So-
cial media taking over the Internet and the latest updates that Google
continues to incorporate into local search, your business either can pros-
per like never before or suffer irreparable harm in the blink of an eye.
A comprehensive marketing plan includes a collection of both
online (Internet, email, social media) and offline (TV, newspapers, direct
mail) marketing strategies designed to get the word out in your local
area. This plan is streamlined to target consumers in the marketing me-
dium they are most comfortable using, rather than aiming wildly with
anything and everything available and hoping that something will stick.
How you choose to spread the word is critical to the long-term success of
your practice in a highly competitive orthodontic marketplace. “PR” no
longer means public relations; it stands for “perception and reality.”
If you do not promote yourself exactly the way you want your
business perceived in the marketplace, no one else is going to do it for
you, especially when up against Savvy online marketing competitors.
Connecting the Dots
There is a continuing debate today on which type of marketing
medium is king among today’s tech savvy consumers. As an Internet
marketing consultant, I do not preach that online marketing is better than
any single marketing medium. My concern is that the different marketing
mediums are not connecting with one another for maximum results. The
GAP between them, if bridged, would optimize how they flow and work
together as one.
It is an inconvenient truth that marketing via multiple media
types is a far better strategy for any business rather than relying too heav-
ily on just one. Unfortunately, many practices experienced this problem
too late, especially in the current economic climate. So many practices
are either online or offline and rarely venture across the gap in an intelli-
gent way that takes advantage of all mediums congruently. Understand-
ing your practice demographic and communication preferences for each
age group will help you develop the most effective marketing strategies
for optimum results.
Prospective new patients or parents often are required to travel
across many marketing mediums to connect with your practice, such as:
* Newspaper ads, direct mail campaign or email blasts
to your website for more information;
46
Miller
• Phone opportunities to schedule a complimentary
consultation;
• Word of mouth search for more information on Goo-
gle, Yahoo or Bing;
• Read a review on a local search;
• Find your website or blog post;
• Watch a YouTube Video;
• Send them to your website to find a phone number for
a free consultation;
• Blog post;
• Facebook;
• Twitter; and/or
• WebSite.
With all the different scenarios, your future patient families are expected
to jump through hoops to find you and in the process, they also find your
online competitors. What if the marketing program of your competition
is more engaging?
What Does This Mean?
This multi-media circus is forcing new patient prospects to be-
come acrobats as they try to follow your sales path toward the goal you
have in mind with the outcome they seek. The bad news is most business
owners and marketers are not making this journey any easier for the pro-
spective new patient. In fact, many new patients are lost in the gap if
programs are not set up and integrated correctly to promote your busi-
116SS.
The Internet marketing landscape has changed dramatically in
2010, much more so than in previous years, especially in search market-
ing and, specifically, local search. Offline internal and external market-
ing strategies have remained relatively static. Between the growth of so-
cial media, the release of search innovations and the increase in local
search habits by consumers online, the current marketing climate hardly
is recognizable from its state just a short time ago. This evolving envi-
ronment challenges marketers and generates speculation as to what is
coming next.
SEO has been an essential component of many successful Inter-
net marketing programs for more than a decade, but despite the proven
return on investment (ROI) capabilities of SEO, there is a surprisingly
47
Internet Marketing Plan
large percentage of practices that have not implemented this marketing
strategy into their programs.
The growing traffic and popularity of social media has some of
the most loyal search marketers questioning the future of search. How-
ever, search engines are still receiving billions of searches per month.
Most recent Internet marketing reports rate SEO a better choice than so-
cial networking when attracting new patients. If you overlook SEO
strategies, your competitors would be happy to take your place in the
rankings and capitalize on new patient traffic you could have been at-
tracting yourself.
The key to success in today’s Internet market is to focus on man-
aging the many changes in the search, social media and mobile climate
as well as targeting consumers that respond to more traditional offline
marketing modalities such as newspapers, TV and direct mail.
Put simply, to expose your business to all opportunities available
today, incorporate marketing campaigns to include offline, online and
mobile worlds, which all work in sync to cast your marketing message
out and reel in as many new patients as you can in a highly competitive
orthodontic market.
Quality new patients want to follow the Yellow Brick Road to
your front door, not navigate through hoops to find you. Nothing I am
saying is actually new here; we are simply looking at all the marketing
options to try to connect the dots, such as:
Blogging
* Do you regularly post at least twice per month on or-
thodontic or dental content of interest to consumers?
* Do your blog posts create back links to improve your
website ranking and increase exposure on the Internet?
* Are you running Internet contests from your blog to
control the traffic to your website, Facebook, You-
Tube and other Internet mediums to increase your ex-
posure and dominate Google?
Do Your Blog Posts Automatically Post to Facebook?
• Video on YouTube: Is your setup for both your You-
Tube site and individual video search engine opti-
mized to be found on page one in a local search?
48
Miller
Marketing with Facebook
* Do you have a business welcome page greeting new
patients with a practice overview branded to match
your website or do you leave it up to them to try and
decipher your wall?
* Are less than 20% of your postings promoting your
practice?
* Do you concentrate on interesting content for every-
one rather than discussing who is getting their braces
on and off?
• What percentage of your patients (active, recall and
retention) actively are participating on Facebook? Is it
a good return on time and investment?
Understanding the logistics of your current Internet marketing
Setup affords you the opportunity to step back, evaluate and reconnect
with your current strategies. What are the goals of your Internet market-
ing program: increasing new patients, practice branding and reputation,
or both? Are your marketing dollars targeting areas for best?
Evaluate your goals objectively and then create a strategic pro-
gram that works best for you online, offline and in a well-rounded pro-
gram targeting all ages and communication styles for best results.
ADDITIONAL STATISTICS WORTH CONSIDERING
WHEN CONNECTING THE DOTS
In the United States, 250 million people have cell phones, equal-
ing 82% of the population.
• Four out of five teens carry a wireless device and the
majority (57%) views their cell phone as the key to
their social life.
* Two thirds of mobile phone users are active users of
text messaging. This observation means 1.8 billion
people actively text today. Globally, there are twice
as many active users of text messaging than there are
active users of email.
* The average open rate (a measure primarily used by
marketers as an indication of how many people
“view” or “open” the commercial electronic mail they
send out) of an email in the third quarter of 2010 was
49
Internet Marketing Plan
22% with the click-through rate on a link of only
5.9%. The click-through rate is a way of measuring
the success of an online advertising campaign. This
measure is obtained by dividing the “number of users
who clicked on an ad” on a web page by the “number
of times the ad was delivered.” Keep these variables
in mind when determining how much time you spend
creating a newsletter and email blasts to increase traf-
fic to your website vs. other marketing programs in
your office.
* Text messages are read within an average of 15 min-
utes of receipt with a response time within 60 min-
utes. While 65% of email is spam, less than 10% of
texting is spam at the time of this lecture.
* Text messaging research reveals U.S. women ages 12
to 30 years old spend twice as much time with their
cell phones as women 40 and older. Marketing charts
(“Women and Digital Life” study, 2009) reveals more
than 80% of U.S. women now use a wireless device
but only 17% are using a smart phone (i.e., iPhone or
Blackberry).
• The average 2010 direct mail response rate is 1% or
less. If you cover your costs and still make a profit, it
is considered successful. However, if you take that
same budget and utilize it elsewhere (e.g., in a com-
munity Service project, upgrade contests and prizes to
increase word of mouth, or video for your website
available 24/7 indefinitely), will you receive a better
return on investment for the future? Food for
thought....
Additional SEO and Social Media Report Results
• More than half of the marketers polled had no formal
or informal process in place for SEO, even though it
has been around for over ten years.
• The vast majority of in-house staff managing social
media programs have no formal education and mini-
mal understanding on how to implement an integrated
SEO and social media program effectively.
50
Miller
• Mobile search: the majority of businesses report that
mobile search currently has no impact on their busi-
ness. Even though it is in the early stages of devel-
opment and not used commonly as a marketing me-
dium, however, it is expected to impact businesses in
the future.
• Personalized search (refers to search engine’s capabil-
ity to gather search results based on a user’s search
history and typical behavior) launched by Google on
December 2009. The education and healthcare indus-,
tries are the least likely to be impacted negatively. I
have seen no adverse affects so far with my clients
optimized correctly in local areas.
• Video search is the ability for search engines to index
Video content in search results, when relevant, using
consumer keywords. Currently 50% report no impact
on business via video search results. This low re-
sponse may be due to incorrect set-up and difficulties
in measuring results. Businesses, especially in the
healthcare industry, that understand social media and
how it works are reporting better than average results
with video.
* The search engine market is dominated by Google. Its
efficient mathematical algorithm, innovative search
enhancements and obsession with relevance truly sets
them apart from all other search engines. Google cap-
tivates 80% of the search market in the U.S. Loyal
users find it difficult to switch.
Facebook is not the tool of choice to improve SEO page ranking
of your website, but it is effective when branding your practice and reputation.
Why Pay Attention?
The explosion of the use of wireless (iPad) and mobile devices in
the past few years influenced this new update by Google heavily, making
Way for technological advances in this area. If you are thinking about or
Currently are redesigning a new website, I suggest you include a mobile
site design addition to your package and be done with it. If you have a
Website that was updated or created recently, I suggest you consider add-
ing a mobile site in the not-too-distant future.
51
Internet Marketing Plan
• In 2008, the total number of global mobile Internet
users (1.05 billion) surpassed the total number of PC
web users (1 billion) for the first time (WapReview,
2009).
* Smartphone and wireless usage is growing eight
times faster than PC growth for consumer use. In
many third-world countries, it is their only contact
with the outside world.
• According to comScore (2010), 234 million Ameri-
cans age 13 years and older are mobile phone sub-
scribers.
• Mobile Access 2010 Report:
O
There are 47 million-plus daily mobile Inter-
net users in the U.S., according to a Pew In-
ternet and American Life Project report.
In the past year, 38% of U.S. cell phone users
accessed the Internet from their phones. That
is a 13% jump from last year, when 25% of
U.S. cell phone users reported mobile Internet
use. However, this number still is considera-
bly less than mobile users using text messag-
1ng. -
In 2010, only 33% of the total U.S. population
had mobile Internet access. Cost is an issue
for many, especially the young. Only 17% of
mothers have Smartphones. The majority of
use is for business applications.
Take a look at your website via mobile by Smartphone or wire-
less by iPad to determine the following:
* Does your site upload quickly?
* Is your contact information with address and phone
number readily visible?
• Does your video work?
—-mm
→ Figure 5. Multiple listings on search engine results for local keywords
“Braces Macedon” (local area Macedon, NY). Different pages of the same web-
site dominate the page results for local orthodontic keywords.
52
Miller
Flash websites, most flash headers and video in most video for-
mats other than .mpeg4 are not visible on mobile technology or wireless.
Therefore, if your contact information is listed in your flash header or
your practice video is not embedded from YouTube, visitors cannot con-
nect the dots with your marketing information through mobile means.
Ongoing Major Google Places (Maps) Updates (November 17, 2010)
Until now, the same domain listing did not appear more than
twice in search engine results pages (SERPS). Now this limit has up-
dated, which could cause competing sites to lose page ranking (Fig. 5).
Are you a winner or loser with your current coding?
Google braces macedon
About 2,310,000 results (0.19 seconds)
º Everything Orthodontist Rochester Pittsford NY Invisalign Braces Macedon
sº Images Rochester NY orthodontists located in Pittsford, Rochester, and Macedon (New York) Damon
Braces and Invisalign at Get it Straight Orthodontics 14612.
videos º Cached
* News Orthodontist Rochester Pittsford NY Invisalign Braces Macedon.
º Shopping Rochester NY orthodontists located in Pittsford, Rochester, and Macedon (New ...
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Testimonials, orthodontist, Pittsford, NY. Rochester, New York.
Get It Straight orthodontists invite you to read what patients are saying...
geºlºgº -º-º-º-º-º-º-cached
RubberBand Wearl Gett Straight Orthodontics Macedon.
Rochester NY orthodontists located in Pittsford, Rochester, and Macedon (New ...
Show search tools º ºg B Cº -- Cached Similar
* Show more results from get-it-straight com
Brighton, NY
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53
Internet Marketing Plan
CONCLUSIONS
Internet marketing is here to stay and will continue to explode as
a major marketing contender to build your practice. Who knows what the
future will bring as new technology advances both online and offline.
Proactively integrating new trends as they develop into your current
marketing programs, along with connecting the dots for prospective new
patients, will help you expedite and improve how you promote your
business for the future.
REFERENCES
comScore. http://www.comscore.com/Press_Events/Press Releases/2010
/5/com-Score Reports March 2010 U.S. Mobile Subscriber Mar-
ket Share
Doyle J. Marketing Sherpa: 2011 Search Marketing Benchmark Report –
SEO Edition. The Effectiveness of SEO and Social Media Objec-
tives:7-8.
WapReview, MWC09, Feb 2009. http://blog.wapreview.com/3019/
Women in Digital Life Report. May 2009. http://www.srgnet.com/?page
id=2
To contact the author for additional information, please email her
(marykay@orthopreneur.com) or call toll free (877.295.5611).
54
MOBILE DEVICE TRENDS
William D. Engilman
ABSTRACT
The adoption rate of mobile devices and mobile applications is phenomenal and
shows little indication that consumers will grow tired of mobile computing any-
time soon. The extensive proliferation of mobile devices and mobile communi-
cation infrastructure offers new opportunities for practitioners to serve their pa-
tients. Mobile communications hold the potential to deliver new services, sup-
port existing patients and attract new patients. This chapter examines mobile
communication, its growth and how practitioners can put new strategies to work
to serve an increasingly mobile population.
KEY WORDS: mobile communications, mobile devices, mobile applications, mo-
bile health care, mobile trends
Rapid advances in mobile communications technologies and
mobile communication infrastructure are changing everything from the
way we pay our bills to the way we make purchase decisions. In addi-
tion, manufacturers are introducing a wide array of mobile communica-
tions devices that can take advantage of this new infrastructure. At the
same time, service providers are creating new mobile applications that
allow users to locate products and services, make purchases, control
equipment remotely, watch television, generate mobile content, interact
with mobile social networks and entertain themselves, all with a single
device.
Although mobile devices like the iPhone and iPad have gener-
ated much media interest, how can we be sure that mobile computing is
here to stay? Government expenditures and subsidies that support infra-
structure creation are one good indicator that mobile computing is poised
to grow in the near future. In the past two fiscal years, the Obama Ad-
ministration created a $7.3 billion spending commitment for the creation
of broadband infrastructure in rural parts of the United States (Depart-
ment of Agriculture, 2009; Department of Commerce, 2010). The goal is
55
Mobile Device Trends
to introduce high-speed Internet to areas where it either is not available
or only is available at a significant cost to the end-user.
The Federal Communications Commission (FCC), working in
conjunction with the United States Department of Agriculture (USDA),
the Rural Utility Service (RUS) and the National Telecommunications
and Information Agency (NTIA), has determined that wireless Internet
access is preferred highly for this task in that it can be deployed without
significant construction costs, can support a large number of users at a
low per-user cost and access devices are available readily. In certain ar-
eas, wireless Internet access will be used to replace aging copper infra-
structure that is not suitable for the delivery of high-speed Internet. In
other instances, wireless technology will allow users to receive Internet
access (and in some cases, terrestrial telephone service) for the first time.
In addition, the National Broadband Plan (NBP), one outcome of
the Omnibus Broadband Initiative (OBI), recommends the expenditure of
more than $15 billion in the next decade from the current Universal Serv-
ice Fund (USF) to ensure that Americans have appropriate and affordable
access to broadband services throughout the country (Federal Communi-
cations Commission, 2010).
Further, the NBP recommends the provision of targeted funding
to support and expand states’ 3G network coverage for mobile communi-
cations. 3G networks largely are expected to serve as the basis of 4G
coverage in the near future.
THE GROWTH OF MOBILE COMPUTING
In early 2010, the International Telecommunication Union (ITU)
announced that there were 4.6 billion cellular devices in use at the end of
2009; the number of global subscriptions was expected to exceed five
billion in 2010 (International Telecommunications Union, 2010). The
global economic slowdown had no significant impact on the adoption
rate of mobile cellular services; in fact, the ITU noted that the availabil-
ity of advanced mobile devices were driving mobile growth in the devel-
oped world and the delivery of mobile health services and mobile bank-
ing were significant factors in the adoption rate of mobile cellular serv-
ices in developing nations.
Of key importance in the growth of mobile computing are:
1. The emergence of communications standards that
support high data transfer rates;
56
Engilman
2. Miniaturization;
3. The development of low-cost, lightweight-yet-
powerful rechargeable batteries;
4. Low power consumption chipsets that provide sig-
nificant processing power;
5. Improvements in memory and data storage; and
6. Touch screen and gesture-recognition technologies.
The most well-known wireless communications standard for
wireless networking is 802.11, which was developed by the Institute of
Electrical and Electronics Engineers (2010). 802.11 is a set of standards
that governs the way wireless network devices work in the 2.4, 3.6 and 5
GHz frequency ranges. These radio frequencies are unlicensed, which
simply means that the FCC does not require users or devices that use
these frequencies to have a special license or certification.
The 2.4 GHz operating frequency is popular, so many devices
operate within this frequency range. This frequency can penetrate walls
and other solid objects, offers a maximum data transfer speed of 11 Mb/s
and propagates signals for a significant distance. Non-network devices
(e.g., cordless telephones, wireless mice and keyboards, microwave ov-
ens, amateur radios, signaling and monitoring equipment, remote con-
trols and Bluetooth headsets) also operate in this frequency range.
Higher frequencies, like the 3.6 and 5.0 GHz ranges, offer a
maximum data transfer rate of 54 Mb/s, but have trouble penetrating
walls and other solid objects. High frequencies offer a fast data transfer
rate, but only in close proximity when a clear line of sight to the receiver
is available.
802.11n, one of the newest additions to this standard, offers
comparatively high data transfer rates over longer distances. 802.11n
devices operate in both the 2.4 and 5.0 GHz spectrums, but the potential
for signal interference and degradation still is a concern. The 802.11n
standard offers a theoretical maximum data transfer rate of 150 Mb/s at
the higher operating frequency and has a maximum indoor operating
range of more than 200 feet. 802.11b, 802.11g and 802.11n devices often
are compatible with each other.
Device standards like 802.11 mean that different manufacturers
can make devices that interoperate easily and consume a known quantity
of power. Users can be certain that their mobile devices work in many
different circumstances, connect to networks in an easily understandable
way and exchange data at reasonably fast rates.
57
Mobile Device Trends
3G AND 4G NETWORKS
Recently, the terms “3G” and “4G” have received a lot of press
as they relate to cellular voice and data services. 3G refers to a set of
standards published as International Mobile Telecommunications-2000
(IMT-2000). The IMT-2000 documents were used as a framework for
the development of additional standards and improvements designed to
support the third generation of mobile telecommunications. 4G – the
standards for which still are in development – refers to further advances
that represent the evolution of 3G services.
There are no specific standards that produced services now
called 1G and 2G. These designations were applied retrospectively and
refer to the earliest developments in cellular technology. 3G services and
those that came before them were designed to carry voice data to a car-
rier’s cellular network. In contrast, 4G services were designed with non-
voice data transmission as their primary payload.
While carriers use the term 4G and sell 4G services, there is no
precise industry-accepted definition of 4G. Purists prefer to use the term
proto-4G or 3.9G to indicate that the services marketed today have not
received the imprimatur of the standards organizations responsible for
developing and publishing service definitions for use by the industry.
That having been said, there are some distinct comparisons one can make
between 3G services, which emerged around 2001 and 4G services that
became available in limited areas in 2006.
3G Network Characteristics
To meet the standards of a 3G network, according to the defini-
tions and standards publishes in IMT-2000, a network must meet the fol-
lowing minimum standards:
1. The network must offer users a minimum data trans-
fer rate of 200 kb/s over a wide area.
2. The network must be digital.
3. The network must provide voice and video telephone
services.
4. The network may (but is not required to) support
TCP/IP-based applications (International Telecom-
munications Union, 2007a).
Some intermediate developments have advanced the capabilities
of 3G network services, but still do not meet the working definition of
4G services. These services are referred to as 3.5G, 3.75G or sometimes
58
Engilman
3G long-term evolution (LTE). Enhanced 3G services may provide
TCP/IP application support and data transfer rates that exceed 1 Mb/s.
Services such as 3G LTE may raise compatibility issues with older 3G
services and 3G-compliant devices because they are not backward com-
patible with the older 3G and earlier standards.
4G Network Characteristics
Even in the absence of fully defined standards, there are some
accepted conventions for the characteristics of an advanced mobile net-
work. According to the ITU, an advanced cellular network consists of all
of the following:
1. The network is entirely IP-based and packet switched.
2. The network must offer peak data rates of between
100 Mb/s and 1 Gb/s based on the user and applica-
tion.
3. The network must allocate network resources and
available bandwidth dynamically, based on demand.
4. The network must ensure a smooth data handoff when
information travels between carrier networks (Inter-
national Telecommunications Union, 2007b).
The ability to scale resources dynamically is important because
users on IP-based networks typically share the available bandwidth. In
the case of 4G networks, the dynamic allocation of network resources
calls for the network to increase the amount of available bandwidth at
network cells whenever user demand warrants it. In essence, the pro-
posed 4G standards will include minimum quality of service provisions.
Other important developments that created the demand for to-
day’s mobile computing devices include the miniaturization of compo-
nents and significant improvements in battery technologies. Improve-
ments in miniaturization and the introduction of new conductive materi-
als enhance the processing power of small devices. Advances in battery
technology mean that today’s batteries are lighter, safer and more power-
ful than ever. Low-power consumption chips allow mobile devices to
operate longer on a single charge, extending their utility and making the
devices more practical and attractive to users (ICT Results, 2008; Cox,
2009).
One cannot underestimate the impact of advances in memory
and data storage on the development of mobile devices (Kurzweil Accel-
erating Intelligence, 2010). When improved memory, processing power
59
Mobile Device Trends
and data storage are combined, the result is a fast and powerful comput-
ing device. These improvements, in turn, enable the use of complex ap-
plications, including those that process time-sensitive data like Voice and
streaming video, touch screen controls and gesture recognition. This ex-
ceptional combination of power, speed and storage space allows both
devices and applications to provide a meaningful user experience.
The final element in this mix is cost. Manufacturers and service
providers alike are keenly aware that the demand for mobile devices is
driven largely by the cost of the technologies and the cost of service.
High entry costs reduce the number of consumers dramatically. By mak-
ing low-cost, high-performance mobile devices that operate on widely
available, relatively low cost networks, manufacturers reasoned that the
demand for wireless services would grow significantly and that is exactly
what has happened.
It should come as no surprise that the adoption of mobile devices
increased dramatically once capable, affordable mobile devices met up
with capable, affordable wireless networking services. If one looked at
the adoption rates of computing technology in the last fifty years, one
will find that the most significant adoption rates have been measured in
just the last few years.
Thomas Watson, Jr., once the head of IBM, often is misquoted
as saying in 1943 that he believed, “There was a world market for about
five computers.” No credible evidence suggests that Watson ever made
such a remark, but it is safe to assume that neither he nor anyone else in
1943 could have predicted a worldwide demand of nearly two billion
mobile devices (Maney, 2003).
Initially, computers occupied entire rooms, were reserved only
for the largest business enterprises and academic environments and could
cost millions of dollars. Beginning in the early 1950s, IBM built a market
for its mainframe computers. Although IBM competed with seven other
major manufacturers, combined demand for the computers reached per-
haps 10,000 units (Maps of World, 2007a). With the development of the
minicomputer in the 1960s, demand for computing power edged upward,
but full-fledged business computing was still a speck on the horizon.
Digital Equipment Corporation (DEC), the company that pio-
neered and popularized the minicomputer in the late 1960s, carved a
niche for itself in the growing market of business computing. When its
minicomputer first was introduced, it sold about 40,000 of the devices
almost immediately (Maps of World, 2007b). Throughout the 1970s,
60
Engilman
computing devices became both more powerful and less expensive, and
offered a favorable alternative to mainframe computing. By the late
1970s, minicomputer sales outpaced mainframe sales by a ratio of about
12:1. Even so, fewer than 85,000 minicomputers were sold in 1979 (Pel-
key, 2007).
During the same time period, advances in telecommunications
perfected innovations like digital subscriber services, which had been
introduced in the 1960s. At the time, the telecommunications carriers
could have – but did not – offer these services to end-users. Instead, the
digitization of voice data largely was reserved for business use and for
backhaul — the movement of large volumes of aggregated data from Point
A to Point B along the carrier’s long-haul networks.
The first personal computers were in production by the mid-
1970s. By 1980, the combined annual market for personal computers
exceeded one million units per year (Reimer, 2005a). This increased
number of units represents the point at which computers had been minia-
turized and reduced in cost such that both businesses and individual users
could afford them. .
By 1984, manufacturers were selling more than six million units
per year. By 1994, consumers were purchasing computers at the rate of
40 million units per year. In just ten years, the demand for personal com-
puters had increased by nearly 700 percent. By 2004, annual PC sales
reached nearly 175,000,000 units (Reimer, 2005b).
The demand has yet to abate. In 2009, PC sales exceeded 300
million units for the first time and demand was expected to grow 20% to
more than 366 million units in 2010 (Gartner Research, 2010). Portable
computers like netbooks and notebooks will contribute significantly to
the seemingly insatiable demand for personal computers. By 2012,
worldwide PC sales are expected to reach 440 million. That forecast re-
cently was revised downward to account for the significant growth in the
sales of mobile devices – specifically tablet computers (Gartner Research,
2011). Consumers now fuel a worldwide demand for desktop and laptop
computers that is poised to exceed one half billion units per year by
2013.
Since the early 1980s, computers have been integrated into the
educational system at all levels, the result of which is a generation of
users who expect a ubiquitous, competent computing experience wher-
ever they go. This expectation is driven in part by innovations like the
World Wide Web, which itself is just a scant 20 years old. Users rou-
61
Mobile Device Trends
tinely turn to the Internet for news, information, commerce, entertain-
ment, education and even companionship. The Internet is available 24
hours per day, seven days per week seemingly for the sole purpose of
providing for the needs of each individual user. The mantra of the Inter-
net is, “It’s all here!” The Internet offers a level of openness and utility
that few other institutions can offer.
The expectation of a ubiquitous, competent user experience also
is driven by applications like search engines, which dedicate themselves
not just to finding what the user is looking for, but also to predicting
what the user wants (Munchbach, 2008). Search engines comb a remark-
able amount of data to supply information for which the user is looking.
In true “Wizard of Oz” fashion, search engine companies decidedly are
un-open about what they do and how they do it. For search engines, “Pay
no attention to the man behind the curtain” is de rigueur, but they control
much of what the user sees on the Web and, by default, the mobile Web.
In the process of divining what a user wants, the search engines
have created new industries designed to make the most of what the user
sees. Search engine optimization (SEO) – a method of creating content
that is attractive especially to search engines and local searches – focused
searches based on the user’s geographic location, context-sensitive
search engine advertising and location-based services all were unheard of
just ten years ago.
The owners of the billions of mobile devices in use now are fuel-
ing the demand for mobile computing. According to Cisco, mobile net-
work traffic has nearly tripled each year between 2008 and 2010. In 2010
alone, global mobile data traffic grew 2.6-fold compared to 2009. Ex-
perts predicted that the growth rate of global mobile traffic in 2010
would be 1.49%; the actual growth rate was 159% (Cisco, 2011).
Areas of growth in mobile traffic include video. In 2010, mobile
video traffic comprised more than 50% of all global mobile data for the
first time. In 2009, video accounted for 49.8% of mobile data and is pre-
dicted to account for nearly 53% of all mobile traffic in 2011 (Cisco, 2011).
When it comes to mobile, fast connections are the order of the
day. Connection speeds among mobile users doubled in 2010. Globally,
the average mobile connection in 2010 was made at 215 Kb/s compared
to an average connection speed of just over 100 Kb/s in 2009. Among
Smartphone users, the average connection speed exceeded 1 Mb/s, up
from 625 Kb/s in 2009 (Cisco, 2011).
62
Engilman
Smartphones play, and will continue to play, a growing role in
the adoption of mobile services. Currently, Smartphones account for
13% of mobile devices but generate nearly 80% of global handset traffic.
In 2010, Smartphones generated on average 24 times the amount of mobile
data that more traditional, feature-based mobile handsets did (Cisco, 2011).
Choice in Smartphones also is driving the demand for Smart-
phones and mobile services. While the iPhone is identified almost uni-
versally as the Smartphone of choice and experts wonder who will come
up with the “iPhone killer,” sales of Android phones are equal approxi-
mately to those of the iPhone (Cisco, 2011). p
Confirmation of this phenomenon can be seen in the amount of
traffic that the Smartphones generate. At the beginning of 2010, iPhones
generated four times more global mobile traffic than did their closest
Smartphone competitor. By the end of 2010, the vaunted iPhone gener-
ated just 1.75 times the amount of mobile data of its closest Smartphone
competitor. Given that the amount of Smartphone data traffic is not drop-
ping, it is clear that highly desirable and competitive options to the
iPhone have entered the marketplace (Cisco, 2011).
Smartphones are not the only devices competing for space on the
mobile landscape. In 2010, non-Smartphone mobile use also increased
2.2-fold. Non-Smartphone mobile handsets add an average of 3.3 Mb of
data per month to the global mobile networks. Add to that the more than
three million tablet computers that now are connected to mobile net-
Works. On average, tablet computers generate five times as much data as
Smartphones do and 40 times as much data as traditional mobile hand-
sets (Cisco, 2011).
Far and away, laptop computers still reign supreme in the world
of mobile computing. With an installed user base approaching 100 mil-
lion, laptops generated an average of 1.7 GB of mobile data per month in
2010, compared to 1.1 GB of data monthly in 2009 (Cisco, 2011).
If more people use laptops, and laptops generate significantly
more data than Smartphones do, why is everyone focused on Smart-
phones? The answer is not all that complex. Smartphones and tablets
travel better than do laptops. They are more mobile. Smartphones and
tablets can go places and do things that laptops, for everything they can
do, cannot do comfortably.
Need directions while driving? Want to do a quick restaurant
search? Send a quick email? Check your bank account balance? You can-
63
Mobile Device Trends
not boot up your laptop while driving or walking down the street, and
even if you could, would it have access to a network? Would the network
be secure? Not without additional hardware or built-in 3G/4G capabili-
ties. In contrast, Smartphones always are connected to the network and
enable people to do simple tasks in one minute or less. They meet the
user’s need for responsiveness in ways that larger computing devices do
not and cannot.
Mobile devices have combined the best of telecommunications
Services, electronics and computer science to create powerful, light-
weight, user-friendly devices, applications and services that meet the
needs of users who simply know nothing of life outside the Information
Age. The same devices also appeal strongly to those who remember
“how it was done in the old days” and have no desire to go back.
Here’s something to consider: 48 million people who do not
have electricity at home have mobile phones. By itself, that statistic
makes an elegant statement about the way mobile devices empower peo-
ple who never have had access to the basic trappings of life in the 21st
century. It also explains why mobile computing is here to stay.
MAKING YOUR WAY ON THE MOBILE WEB
The mobile Web is here to stay. In the same way you look to the
Web for services that are valuable, as a service provider, you also need to
provide value for those seeking your services. One easy way to make
your mark on the mobile Web is to start with your existing Web page.
How does your existing website appear to a mobile browser'? If you have
never asked that question, there is a good chance that your website does
not look good. This is unfortunate because the mobile-friendliness of
your Web page either can move you up or down in the mobile search
engine rankings when people look for your services (but not necessarily
you specifically) using a mobile browser. Mobile browsers do not always
handle JavaScript, Flash or even cascaded style sheets (CSS) correctly;
sometimes they do not handle them at all.
The quickest and kindest thing to do in this case is to remove all
of these things from your site. Removing them from your site, however,
means that you will be removing them from users who come to you via a
desktop computer with a fully functional browser that can manage all of
these things. So who do you aim for – the mobile or non-mobile user?
What does a mobile-friendly Web page even look like? If you change
your website to accommodate mobile browsers, will that impact your
64
Engilman
search engine rankings for non-mobile searchers? Can your website de-
liver one set of pages for mobile browsers and another set for non-mobile
users?
The short answer is that you can make Web pages that are served
up to the user based upon the kind of device they use. Your site can de-
tect the user’s browser type and issue one layout for the user who is
browsing from a desktop computer and another layout for users who are
searching for your services on a Smartphone.
By improving your site to detect the way in which users search
for you and then accommodating their search devices, you can accom-
plish at least two things: improving your mobile search engine rankings
and improving your customer service.
Improving your search engine rankings is huge. When someone
is looking for an orthodontist in your local area, the best place to be is on
the first page of the search engine results. Why? No one but the most
dedicated searcher goes to the second page of search results and virtually
no one at all goes to the third page. If your practice is listed on the fourth
page of the results, you will never be seen.
With simple changes, you can ensure the efficient delivery of in-
formation to customers and potential customers, no matter how they
come to you. This increased visibility will be a big help to the mother
who is looking for your office phone number while driving or the new
patient who is unsure how to find your office. It also preserves the func-
tion of your website for the user whose browser is prepared to take it all
111.
How can you check your website to see whether or not it is mo-
bile-friendly? The World Wide Web Consortium (W3C) offers the W3C
mobileOK Checker, an online tool that will assess your website and
quantify how mobile-friendly your website really is. The tool is located
at http://validator.w3.org/mobile/.
Simply type in the URL of your website and the mobileOK
Checker will rate your site in terms of critical, severe, medium and low
failures in specific categories. The mobileOK Checker will evaluate your
site for its use of standard HTML, the size of the pages on your site, the
network usage your site requires and how well you have considered the
mobile user when it comes to page design.
If you manage your own website and are good with HTML and
basic computer programming, you can modify your existing site rela-
65
Mobile Device Trends
tively painlessly by setting up a “mirror” domain for mobile users, and
adding a little bit of code that detects and responds to the type of browser
from which a request for information is coming.
Your Web server will refer mobile users to your mobile domain
and skip the programming that might trip up the mobile browser. In mo-
bile browsing, simpler is always better. If the Web server determines that
an information request is coming from a non-mobile user, it will serve up
the site exactly as it always has in the past.
So what goes into making a mobile-friendly page? Mobile
browsers are big on simplicity so they like standard HTML and plain
text. They do not like long URLs, JavaScript, cascaded style sheets, an-
chored images, scripts and all of the other things you may have added to
your site to make it attractive. •
Remember, the average mobile connection in 2010 was 215
Kb/s. Smartphones have much better data rates – more like 1 Mb/s, but a
graphics-intensive website quickly will overwhelm a mobile browser.
Removing these things for the sake of a mobile browser also signifi-
cantly decreases the mobile browser's download time and improves the
mobile user’s experience. In the end, meeting the user’s needs is what it
is all about.
If you have concerns that your page will not look first-rate, a
good thought to keep in mind is that mobile users primarily are interested
in getting fast, accurate information. With mobile computing, function is
king. Esthetics matter only to the extent that they support the user’s pri-
mary mission of getting information.
If someone manages your website content, let him/her know that
you want to make your site friendly to mobile browsers. Again, the
modifications are simple and can be tailored to deliver content to specific
mobile devices if you want to add that level of detail. While this may
sound complicated and/or expensive, it is not.
MOBILE WEBSITE RESOURCES
If you are interested in exploring a tutorial on the subject or
learning more about making mobile friendly Web pages, you can visit
http://www.mikeindustries.com/blog/archive/2005/07/make-your-site-
mobile-friendly. This URL is somewhat out of date, but you can get a
feel for what to do to make your site more mobile friendly.
66
Engilman
Google offers the Google Mobilizer, which allows a user to enter
a URL. The Mobilizer then returns a mobile-friendly version of the page
by stripping out all potentially mobile-unfriendly HTML code. This ap-
proach requires nothing of the site provider and everything of the user. If
your user does not know about Mobilizer or does not take the time to do
this, you will lose out in mobile searches. The Mobilizer is located at
http://www.google.com/gwt/n.
Search Engine Optimization Basics
When you are finished thinking about how the mobile browser
sees your website, take a few minutes to think about how the search en-
gine sees your site. The search engine can be your best friend or your
worst enemy when it comes to doing business on the Web, so providing
the search engine with what it wants is a great way to ensure that your
potential patients can find you easily.
If you perform a Google search for orthodontist [ZIP code] and
fill in the brackets with your ZIP code (or city), where does your practice
fall in the search engine results? If you have never stopped to consider
your search result position, think about this: some of your competitors
have thought about it and have taken steps to ensure that their website
appears higher in the results than yours does. If you want to know who is
thinking ahead of you, look at the advertising (also known as “sponsored
links”) in the search results.
Search engines make decisions about page rank based on “rele-
vance.” As mentioned earlier, relevance is determined by a proprietary
formula that the major search engines are loath to reveal. Google says
that its relevancy formula considers more than 200 factors. Not all fac-
tors are deemed equal, of course. Observers note that certain actions have
an impact on how the search engine sees a website and interprets the
2 66
site’s “relevance” to a particular search term or phrase.
Generally speaking, placement in the search engine results can
be improved by taking some relatively standard steps. Google has pub-
lished its Webmaster Guidelines, which provide specific details on what
improves your page from Google’s standpoint. This guide is updated pe-
riodically as Google updates its ranking algorithms.
Google favors sites that are text oriented and that use standard
HTML structure. Title tags, Alt tags, links from other sites related to
yours, indexing and the use of keywords within the site text also help
improve your page’s rank in Google. Conversely, broken links on your
67
Mobile Device Trends
site, the use of images in favor of text, the lack of Title and Alt tags,
links from irrelevant external sites and non-standard HTML usage can
damage your Google rank (Google, 2011).
Google differentiates between mobile and non-mobile browsers,
so domains that offer a mobile-friendly version will be ranked higher
when a mobile browser requests information. Mobile friendliness will
not necessarily help your page rank if the searcher is coming from a non-
mobile browser, but if your overall site traffic increases because you of
fer a mobile-friendly version of your site, your overall rank may move up
simply because you are receiving more site visitors.
Good placement in search engines is the result of a consistent ef-
fort on a site owner’s part to make sure that the site contains highly valu-
able, fresh content that is relevant to search requests. Regularly adding
new content and updating existing content will ensure that the search
engine “spiders” – which visit and review page content — come back to
your site often.
If you hire someone to do search engine optimization (SEO) for
your site, understand that no one can guarantee your business a number
one position in Google searches except Google, and not even they do
that, even for their Ad Words customers. Avoid firms that promise oth-
erwise. Do not resort to illegitimate techniques to drive traffic to your
site. Avoid firms that generate meaningless links to your site; Google
will penalize your site for using techniques that attempt to inflate your
site rankings artificially.
MOBILE SEARCH: WHO IS LOOKING FOR YOU2
Mobile search holds the potential to drive a lot of actual traffic
into your business. Searching is a major component of mobile traffic, so
it makes sense to prepare your site to handle visitors who come to you
through routes other than your traditional referral network.
In terms of mobile search, Google is the major player and con-
trols 97% of the mobile search market. Yahoo! and Bing divide the re-
maining two percent (Macquarie [USA] Equities Research & Efficient
Frontier, 2011).
Not surprisingly, Google receives nearly all its revenue from
paid mobile advertising. In that mobile search comprises about 15% of
all search volume through Google, it makes sense to pay close attention
to Google’s guidelines when designing your mobile site or buying a mo-
bile-oriented advertising campaign.
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Engilman
According to Google, mobile search volume grew 500% be-
tween 2008-2010 (Sterling, 2010). This rate of growth is consistent with
the adoption rates of mobile devices and indicates that search plays an
important role in the mobile user’s experience. Local searching is espe-
cially important because mobile users are more likely to act on their
search results. Local advertising, mapping and click-to-call features are
targeted specifically toward mobile searchers.
Regardless of how you access Google, the search engine
“knows” where you are geographically, based upon the IP address asso-
ciated with your query. Using this information, the search engine can
supply context-relevant local advertising and information in its search results.
Mobile search can take geo-location even farther. Rather than
simply displaying local advertising, Google and other search engines
aggregate data from multiple sources on the subject of a search. A query
on your orthodontic practice may produce links to your site, but the
Search also may bring up data over which you do not have control, such
as a map of your site including the building address, phone number,
street view photos and directions; photographs related to your business;
reviews of your service from other sites; news about you or your prac-
tice; professional development materials you may have created; and serv-
ice and cost comparisons of you and your local competitors.
While you may not control much of the information the search
engines produce about your practice, you can take advantage of the re-
Sources out there to help drive more customers to your site. Talk with
your patients about ratings and reviews. Encourage them to put in a good
word for you on service-related ratings sites.
Take advantage of your professional memberships and include
their certifications on your website. These elements can help boost your
“relevance factor” when it comes to search engine rankings. Consider how
you can incorporate online services, such as online appointment schedul-
ing or online bill payment. Busy customers may not have time during the
day to schedule an appointment, but can self-schedule if your website
can provide the information they need. Online payment options may in-
crease your receivables by providing another easy way to pay for serv-
1CCS.
Friending on Facebook, Tweeting on Twitter: The Top Mobile Apps
If you are ready to go beyond the search engine, you also can
take advantage of mobile applications to build a social network for your
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Mobile Device Trends
business. If you are not already on Facebook, you can open a free Face-
book account that will enable you to see connections between you and
your “Facebook friends.” It also will allow you to see connections be-
tween your Facebook friends and their Facebook friends.
For businesses, Facebook is an interesting tool. You can make a
“fan page” for your business and your patients who use Facebook can
join your list of Facebook fans. On your business page, you can help
keep patients up to date on changes to your practice, new products or
services you offer, special offers, or events and activities in which you
participate.
Depending on how you use your Facebook page, it can become a
good word-of-mouth referral system that is driven by your existing pa-
tients to help you reach out to their friends, family and neighbors. An-
other benefit is that Facebook currently is the number one mobile appli-
cation in use in the world.
Google Maps is the number two mobile application, so it is a
good idea to spend some time with it. If you do nothing else, take a min-
ute to claim your business listing on Google Places. By claiming your
business listing, you can ensure that the search engine has the correct
information about your business. You also can add photographs of your
choosing, make special offers to first-time or returning visitors and get
information about who is searching for your business. Business listings
on Google Places are free.
The Weather Channel and Pandora Radio currently occupy the
third and fourth spots in terms of mobile application popularity. While
there is not much you can do to take advantage of these sites, it should be
noted that mobile users are interested keenly in the weather and personal-
ized radio stations. Use this observation as a cue to add a little weather
bug or a link to Pandora Radio to your site; some of your mobile users
may appreciate it.
Google Search rounds out the list of the top five mobile applica-
tions. It should be noted however, that more than half of the Google
searches conducted by iPhone users come from the browser toolbar.
About 40% of Google searches coming from the iPhone come from the
Google home page and only 10% of Google’s mobile searches on the
iPhone come from the Google Search application. If you have claimed
your business listing and have done a good job of making your site visi-
ble to Google, you will get a lot of traffic from Google Search without
doing anything special.
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Engilman
Social Networking and Your Practice
Users – mobile or otherwise – have gravitated to social network
sites because they put users in contact with other people who share the
same interests, have the same problems or need the same information. Ad
hoc social groups form all the time on social networks, but it can be a
great way to maintain personalized contact with your patients.
Facebook now offers good filtering that enables you to separate
your business network from your personal and professional social net-
works. You can publish something to your personal page that only your
friends and family will see and information to your business site that
only your patients will see. If you are unsure about setting permissions,
Facebook offers a tool that will show you exactly what someone on your
“friend list” will see. You can tailor your settings to suit your needs.
Twitter is an interesting site that takes advantage of the short-
message service (SMS) protocol to send out brief messages to people
who “follow” you on the service. You can “tweet” patients about new
products and services, general reminders, new developments, news or
anything you like. The maximum message size is 160 characters, so if
you use Twitter, remember, “Brevity is the soul of wit.”
Augmented Reality: For Real?
Augmented reality is a relatively new addition to mobile com-
puting. Augmented reality is defined loosely as real information that is
augmented by computer generated imagery or information. Currently,
augmented reality is being used experimentally in advertising, context-
sensitive help, navigation, local search, entertainment and fieldwork.
Other applications may include augmented reality in remote device con-
trol, medical imaging, and design and development work.
Augmented reality applications are not developed thoroughly at
this time, but applications soon may exist to help orthodontists enhance
treatment plans and help patients visualize post-treatment results.
Location-based Services
One of the darlings of mobile applications is location-based serv-
ices which are interesting especially to mobile users because they are
designed to make the best use of mobility. Location-based services cur-
rently include information and alerts, navigation assistance, people find-
ing, traffic monitoring, instant advertising, couponing and other time-
sensitive applications.
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Mobile Device Trends
Some businesses are turning to location-based services as a new
revenue stream. By offering instant deals and discounts, loyalty bonuses
and coupons, businesses can take advantage of mobile users in the im-
mediate area who are prepared to make purchases.
At first blush, location-based services do not seem to offer much
promise for orthodontic practices; however, instant advertising always is
possible. Location-based services also may be used to provide instant
reminders of upcoming appointments when your patients happen to be in
the vicinity of your office.
Applications like Foursquare may not be all that useful for pro-
moting your practice, but you may find that you can reach your patients
with other mobile apps like Brightkite. Brightkite’s business functions
are designed to help you reach out to your customers and personalize
your business contact with them.
Some mobile applications have limited utility because they only
work on certain devices. If you plan to begin offering location-based
Services or use location-based communications tools, be sure that the
app(s) you choose will allow you to reach a large number of patients.
Another consideration is the amount of time it may take to up-
date several different online patient connection points. If you have a
Facebook page and a Twitter feed, an application like Gypsii will allow
you to update both feeds simultaneously from one location.
IS E-COMMERCE COMING TO A PRACTICE
NEAR YOU”
Electronic commerce (e-commerce) may be one area in which
your administrative procedures change directly due to mobile technol-
ogy. One of the interesting features of mobile devices is that some of
them possess the ability to link to the user’s credit account. Users simply
transfer payments to a merchant via their mobile phone instead of swip-
ing a credit card or writing a check.
In the relatively near future, your practice may be faced with the
reality of handling mobile payments. Near-field communications (NFC)
technologies are being incorporated into credit cards and mobile devices.
NFC chips work in a range of 4 cm or less and can authorize payments
from credit cards or bank accounts. In addition to completing payments,
NFC technologies can be used for mobile advertising, near-field net-
working and electronic key applications.
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Engilman
In late 2010, the three largest mobile carriers in the United States
agreed to participate in the joint development of a standard platform to
affect the use of NFC technology for mobile payments (Clark, 2010). A
widely accepted mobile payment platform means that this standardized
technology will be built into a significant number of mobile devices in
the near future.
In addition to the carrier support, both Google and Apple have
said that their future mobile devices (specifically the Android phones, the
iPhone and the iPad) will support NFC for the purpose of mobile pay-
ments (Kharif, 2011). For older mobile devices, the payment platform
will be extended through the use of microSD cards. Any mobile device
that can accept a microSD card can be turned into a mobile payment de-
vice. While mobile payments are not here yet, it is clear that they will be
in the near future.
You may need to modify your merchant account services to in-
clude the ability to accept mobile payments. In the meantime, you can
investigate more traditional e-commerce solutions that allow your pa-
tients to make online payments from their credit cards or checking accounts.
Quick! What's a QR Code?
You have seen QR codes, even if you do not know what they
are. A Quick Response (QR) code is a next-generation two-dimensional
(2D) bar code that encapsulates information (http://prepressure.com). QR
codes originally were designed for manufacturing and store machine-
readable information. Camera phones equipped with QR reader software
can decipher the barcode and take certain actions, like display a text
message, open a Web page, send an email or exchange a vCard with the
user’s mobile device.
QR codes are taking on a new life outside of manufacturing.
Businesses now are using QR codes to supply additional information to
mobile device users on advertising, business cards, email marketing and
more. QR codes can contain anything from text information to special
offers. To generate a QR code, visit: http://qrcode.kaywa.com/.
Other free QR code generators can be found online. Once your
information has been encoded, you can save the code to your hard disk in
a standard file format and then reprint it on business cards, payment cou-
pons, advertising or on whatever you like. The QR code can encode
many different types of information and can accommodate a variety of
both inventive and ordinary uses.
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Mobile Device Trends
Gaming
Gaming and social gaming both play a big role in driving the
adoption of mobile devices. Many users choose to load games onto their
mobile devices. Social gaming adds the ability to play with or interact
with certain other players. Often, the object of a social game is the game
experience itself. To complete the game objectives, a user often must
seek help from friends, acquaintances or other players whom they may or
may not know in “real life.”
The attraction of games and gaming is powerful, but you may
not want to develop online social relationships with patients. That does
not mean that you cannot use the attraction of games and gaming in your
practice. Consider this: if you have a busy practice and encounter delays
in delivering services to patients due to scheduling mishaps or chroni-
cally late patients, think about adding a few iPads or other tablets to your
waiting room. If you are running behind schedule, your younger patients
may appreciate the break. You also may find that your patients start ar-
riving a little early for their appointments to ensure they have time for
some Angry Birds or Labyrinth Lite.
Mobile Applications: A Broad Base
There are a significant number of mobile applications available
for download. Many applications (“apps”) are free or available for a
nominal charge. Apps enable Smartphones and tablets to perform tasks
from navigation to calculating instantaneous gas mileage based on driv-
ing styles. General Motors (GM) makes a mobile application that can
start a GM vehicle remotely and one of the most popular iPhone applica-
tions brightly illuminates the display screen, turning the iPhone into a
flashlight.
Healthcare professionals also will find a growing body of appli-
cations designed to empower patients with health care information, in-
cluding their personal health care records (AHIMA, 2011a). Microsoft
and Google offer just two of about 30 free Web-based PHR applications
available to individuals. Additional software products and fee-based
services exist as well (AHIMA, 2011b). The AHIMA actively encour-
ages patients to begin and maintain their own personal health records.
Such records may provide invaluable assistance to caregivers
and family members of chronically or terminally ill patients; seniors who
may not have the benefit of nearby relatives; travelers who become ill or
74
Engilman
injured while away from home; students who live away from home while
studying; and children who may require medical assistance while at
school, or who are under the care of multiple providers.
Over time, mobile devices are expected to play a greater role in
the creation, maintenance and access of personal healthcare records. As a
healthcare provider, your patients may turn to you for advice and infor-
mation about their care and treatment plans, and may ask you to assist
them in the creation of their personal healthcare records. Minimally, you
should review you practice policies on providing information to patients from
their medical records and assess your ability to deliver it in a digital format.
CONCLUSIONS
Mobile devices definitely are a part of today’s landscape and will
continue to play an important role in the way people live, work, learn and
play. There are significant opportunities to incorporate mobile devices
and mobile device friendly practices into your business. In addition to
supporting your ability to deliver services, mobile devices can help pro-
mote your practice, maintain contact with patients, potential patients and
referring practitioners, streamline payment processes and improve cus-
tomer service.
REFERENCES
AHIMA. Choose A PHR. http://myphr.com/resources/choose.aspx.
Searched March 2011 a.
AHIMA. Personal Health Records. http://myphr.com/. Searched March
2011b.
Cisco. Cisco visual networking index: Global mobile data traffic forecast
update 2010-2015. http://www.cisco.com/en/US/solutions/collateral/
ns341/ns325/ns337/ns'705/ns827/white paper c1 1-520862.html (Feb-
ruary 1, 2011).
Clark S. AT&T, Verizon, T-Mobile confirm Isis mobile payments joint
venture. http://www.nearfieldcommunicationsworld.com/2010/11/16/
35043/att-verizon-t-mobile-confirm-isis-mobile-payments-joint-venture/
(November 16, 2010).
Cox J. Growing "power gap" could force Smartphone tradeoffs.
http://www.networkworld.com/news/2009/092809-smartphone-trade-
offs.html (September 28, 2009).
75
Mobile Device Trends
Department of Agriculture. Broadband initiatives program: Broadband
technology opportunities program. Notice. http://www.ntia.doc.gov/
frnotices/2009/FR_BBNOFA_090709.pdf (July 9, 2009).
Department of Commerce. BTOP/NOFA fact sheet_12210.
http://www.broadbandusa.gov/files/BTOP_NOFA Fact_SheetO12210
.pdf (January 22, 2010).
Federal Communications Commission. National Broadband Plan Execu-
tive Summary. http://www.broadband.gov/plan/executive-summary/
(March 16, 2010).
Gartner Research. Gartner lowers PC forecast as consumers diversify
computing needs across devices. http://www.gartner.com/it/page.jsp?
id=1570714 (March 3, 2011).
Gartner Research. Gartner says worldwide PC shipments to grow 20 per-
cent in 2010. http://www.gartner.com/it/page.jsp?id=1313513 (March
4, 2010).
Google. Search Engine Optimization (SEO) webmaster tools help.
http://www.google.com/Support/webmasters/bin/answer.py?answer-3
5291 (March 20, 2011).
Institute of Electrical and Electronics Engineers (IEEE). IEEE 802.11
wireless local area networks. http://standards.ieee.org/about/get/802.
802.11.html (February 15, 2010).
International Telecommunications Union (ITU). ITU defines the future of
mobile communications. http://www.itu.int/newsroom/press_releases/
2007/30.html (October 19, 2007a).
International Telecommunications Union (ITU). ITU global standard for
international mobile telecommunications ‘IMT-Advanced. '
http://www.itu.int/ITUR/index.asp?category=information&rlink=imt-
advanced&lang=en&display=paper (November 16, 2007b).
International Telecommunications Union (ITU). ITU sees 5 billion mo-
bile subscriptions globally in 2010. http://www.itu.int/net/press
office/press_releases/2010/06.aspx (February 15, 2010).
Kharif O. Apple plans service that lets I-phone users pay with handsets.
http://www.bloomberg.com/news/2011-01-25/apple-plans-service-
that-lets-iphone-users-pay-with-handsets.html (January 25, 2011).
Kurzweil Accelerating Intelligence. Silicon nanocrystals break minia-
turization barrier for memory chips. http://www.kurzweilai.net/silicon-
76
Engilman
nanocrystals-break-miniaturization-barrier-for-memory-chips (Septem-
ber 1, 2010).
Macquarie (USA) Equities Research & Efficient Frontier. US internet
mobile search scaling fast: Google dominating. http://www.efrontier.
com/sites/default/files/US_Mobile Search.pdf (March 3, 2011).
Maney K. The Maverick and His Machine: Thomas Watson Sr. and the
Making of IBM. New York, NY: John Wiley & Sons Inc., 2003.
Maps of World. Mainframe Computer. http://www.mapsofWorld.com/
referrals/computers/types-of-computers/mainframe.html (2007a).
Maps of World. Minicomputer. http://www.mapsofWorld.com/
referrals/computers/types-of-computers/minicomputer.html (2007b).
Munchbach A. Google announces ‘Google Instant, ' predictive search
results as you type. http://www.bgr.com/2010/09/08/google-instant/
(September 8, 2010).
Pelkey J. Entrepreneurial Capitalism and Innovation: A History of Com-
puter Communications 1968-1988. http://www.historyofeomputer
communications.info/Book/5/5.1 MinicomputersDistributedDataPro-
cessingMicroprocessors.html (2007).
Prepressure.com. QR (quick response) codes. http://www.prepressure.
com/library/technology/qr-code (March 6, 2010).
Reimer J. Total share: 30 years of personal computer market share fig-
1//’6S. http://arstechnica.com/old/content/2005/12/total-share.ars/3
(December 14, 2005a).
Reimer J. Total Share: 30 years of personal computer market share fig-
1//'éS. http://arstechnica.com/old/content/2005/12/total-share.ars/10
(December 14, 2005b).
Science Daily. Pushing the limits of computer chip miniaturization:
ScienceDaily. http://www.sciencedaily.com/releases/2008/01/0801
12083626.htm (January 14, 2008).
Sterling G. Google: Mobile query growth “dramatically higher ” than
PC. http://searchengineland.com/google-mobile-query-growth-
dramatically-higher-than-pe-38203 (March 16, 2010).
GLOSSARY OF TERMS AND ACRONYMS
3G: Term that refers to current mobile communications and network
standards that are based on voice communication.
77
Mobile Device Trends
4G: Term that refers to future mobile communications and network stan-
dards that are based on data transfer.
Augmented Reality: Real imagery that is augmented by computer-
generated imagery or information.
Brightkite: Mobile application that enables businesses to personalize in-
formation and distribute it to customers, users or clients.
E-commerce: General term to describe purchases and other monetary
transactions that are conducted on the Internet.
Foursquare: A location-based mobile application that supports people-
finding and similar social functions.
Google: Primary Internet search engine. Google controls a significant
share of both mobile search and mobile advertising.
Google Maps: A mapping tool provided by Google that can provide
navigational and location-based information.
GPS: Global Positioning System. Satellite based system that provides
terrestrial navigation data.
Local Search: Internet search that provides search results based on the
user's physical location.
Location-based Services: Services that are delivered via the Internet that
are based on the user's instant location.
Mobile Applications: Software applications that are designed specifically
for use on a mobile device.
Mobile Browser. A web browser designed for use on a mobile device.
Mobile Devices: A portable device that can be carried by an individual
and that can connect to a mobile network. Such devices can send and
receive voice and data information.
Mobile Searching: Search services designed to provide information to
users who are moving as the search is being conducted.
Mobile Web: Web sites and services designed to meet the needs of mo-
bile users.
Personal Health Record: A personally constructed and maintained record
of health services delivered to an individual.
Quick Response Code: A multi-dimensional barcode that stores informa-
tion upon which mobile devices can act.
Search Engine: A tool designed to locate information using the Internet.
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Engilman
Search Engine Ranking: The order in which search engine results are
delivered to the user.
Search Engine Results: The results of a search engine query.
Social Gaming: Multi-player Internet-based games whose primary pur-
pose is to provide social interaction.
Social Networking: Internet-based applications that enable users to inter-
act and share information on a social basis.
79

80
A TELECOMMUNICATIONS PRIMER
William D. Engilman
ABSTRACT
Voice-over Internet Protocol (VoIP) has the potential to support the modern
orthodontic practice by reducing costs, adding customer Service functions and
leveraging the practitioner’s existing data network infrastructure. While VoIP
provides familiar communication services, the adoption of VoIP is not without
concern, however. VoIP differs significantly from the traditional telecommuni-
cations services most practitioners currently use. This chapter examines tradi-
tional telecommunications services, the delivery of digital data across both digi-
tal and analog transmission networks, VoIP technology and its adoption consid-
erations.
KEY WORDS: Voice-over IP, VoIP, IP networking, PSTN, digital communications
Voice-over Internet Protocol (VoIP) is the latest innovation in
telecommunications technology. It seems like a major leap forward when
you consider that telephones have not changed much since Alexander
Graham Bell introduced them in the late 1800s. The biggest innovations
in telephony were designed to support the growth of the public switched
telephone network (PSTN). Throughout its history, however, the basic
assumption underlying the PSTN was that its users would be talking to
each other. The VoIP revolution extends the global PSTN by using the
vast array of interconnected data networks throughout the world.
PSTN in the United States largely was built by AT&T when it
had a monopoly on telephone services. By virtue of its position in tele-
communications, AT&T also was responsible for some of the earliest
modernizations in the telecommunications industry. These moderniza-
tions, originally developed to support the company’s long-haul network,
eventually made their way into the “last mile.” The last mile is the final
leg of copper wire that carries analog phone service to the subscriber.
VoIP eliminates the decades-old fundamental distinction be-
tween voice and data because in the world of digital telephony, voice is
81
A Telecommunications Primer
data. This chapter will discuss the evolution of the PSTN and the innova-
tions that have made VoIP possible. It also will offer a basic explanation
of VoIP services, what modern VoIP services can offer and how you can
incorporate them into your practice.
THE PUBLIC SWITCHED TELEPHONE NETWORK
(PSTN)
PSTN is a generic term used to describe the infrastructure of a
telecommunications provider that sells services to the general public
(Bigelow, 1992). PSTN providers deliver both last-mile service (i.e.,
service directly into the subscriber’s home or office) and long-haul serv-
ice (i.e., access to the toll-, long-distance and international telephone
networks). *
The PSTN uses a system of unique addresses (i.e., phone num-
bers) to route calls to their destinations. In the United States, this system
is known as the North American Numbering Plan (NANP) and is regu-
lated by the Numbering Plan Administrator (NPA).
A telephone number consists of a three-digit area code, a three-
digit exchange and a four-digit station ID. Station is another term for the
end-user’s telephone. The telecommunications companies refer to the
area code as the NPA. The exchange number is known as the NXX and
the combined area code and exchange are called the NPA-NXX. The
NPA-NXX combination is called a rate center, which usually is the
name of the locality. In rural areas, one rate center may cover several
small towns or areas. In smaller cities, one rate center covers the entire
city. Large cities may be divided into several rate centers that may or
may not allow local calls to each other.
The NPA-NXX information is important because it determines
how a telephone call is routed through the PSTN and the premiums that
may apply to the transport. A Canadian website called the Local Calling
Guide (http://localcallingguide.com) is an excellent Internet resource that
identifies the operational components of the PSTN as it exists in the
United States and Canada. The Local Calling Guide will identify the
NPA and NXX of a phone number, local rate centers, incumbent and
competitive local exchange carriers in the area and their Operating Com-
pany Numbers (OCN), cellular networks, switch designations and physi-
cal locations of the telephone switches, local access and transport area
(LATA) definitions and other significant information.
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Engilman
A LATA is a regional calling area in which a telecommunica-
tions provider may offer exchange telecommunications and access serv-
ices. The LATA designation originally was developed when AT&T was
divested of its regional operating companies in 1984. The Local Calling
Guide site is maintained daily and is a comprehensive resource for per-
Sons interested in the PSTN.
To see how the PSTN works, consider a telephone call from end
to end. The subscriber picks up the telephone and dials. The telephone is
connected directly to its rate center switch by copper wiring that enters
the caller’s home or office. The telephone handset converts the caller’s
dialing signals to distinctive tones (or patterns in the case of pulse dial-
ing), which are carried on copper wiring to the central office, the first
switching point in the PSTN.
PSTN switches are located physically at the central office. A
single central office may house hundreds of switches. Because of the
physical limitations of copper, the central office normally is located
within a mile or two of the subscriber’s station. The copper wiring be-
tween the central office and the subscriber’s location is known as the last
mile because most often, it literally is a mile or more in length. This por-
tion of the provider’s copper infrastructure also is known as the local
loop.
The switch decodes the dialing information and determines how
the call must be routed to get to its ultimate destination. The central of
fice switch assumes that an incoming call is local unless the dialing in-
formation is pre-pended with an area code. The switch only knows about
itself, other local rate centers and the toll center, where non-local calls
are sent. It searches its database of other exchanges in its own rate center.
If it finds a match, it hands off the call to the appropriate switch or to the
appropriate station if the call is meant for another of its own stations.
If the dialing information is not pre-pended with an area code
and the switch cannot find the requested local exchange, the switch will
issue an error called an intercept. The intercept, which is accompanied
by some distinctive tones, may be issued even before the caller has com-
pleted the dialing information. A pre-recorded message will inform the
caller that the dialing information is not valid.
If the dialing information is pre-pended by an area code, the
telephone switch hands the call up the network to another switching of-
fice, known as a toll center. The toll center has switches that can “see” a
larger portion of the PSTN and can route calls to other non-local toll cen-
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A Telecommunications Primer
ters within the caller’s LATA, as well as to the primary center, which is
the entry point into the long-distance network. The network then routes
the call back down the network to the recipient’s central office and on to
the correct station.
If the call is a long-distance call, the central office switch will
hand the call up the network to a primary center. The primary center may
need to hand the call to another switching center if the call destination is
in another state or on another carrier’s network, or forward the call to a
long-distance switch closer to its final destination if the destination is
also on the originating network or in the same state. The call proceeds
back down the PSTN until it is routed to the correct receiving station.
In much the same way, international calls carry additional dialing
information and are routed to international carriers, then to the appropriate
country, then into the PSTN in the recipient country for final routing.
CIRCUIT-SWITCHED NETWORKING
No matter how a call is routed through the PSTN, a completed
call – one in which two stations are connected – forms a temporary pri-
vate pathway, called a circuit, between the two stations (Hioki, 1990).
The PSTN resources devoted to that circuit cannot be used for any other
calls until the two parties disconnect from the network. More parties can
be added to the circuit — such as is the case with three-way calling – only
through the use of additional resources that bridge more stations into the
circuit. Once the parties disconnect, the physical resources used by the
temporary circuit can be reassigned to other calls.
Each temporary circuit (phone call) represents the use of some
of the physical resources of the telecommunications carrier. Periodically,
the physical resources of the carrier will be consumed completely, mean-
ing no new circuits can be made at the instant a caller tries to place a call.
In this case, the caller will receive an intercept stating, “All circuits are
busy. Please hang up and try your call again later.” The exclusive con-
sumption of physical resources represents one way in which telephone
calls can be routed from place to place. It also is the source of one of the
biggest disadvantages of the PSTN.
Digital Services on the PSTN
A variety of digital services, typically delivered over copper in-
frastructure, are available through the regulated telecommunications car-
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riers. This section offers a brief explanation of some of the most popular
services and the major differences between them.
Asynchronous Digital Subscriber Line (ADSL)
The digital phone services we use today as consumers – primar-
ily DSL, ISDN and T1 lines – were developed as part of a much larger
effort to digitize voice traffic. Initially, DSL services were designed to
help the phone company move large Volumes of Voice traffic easily and
inexpensively through its long-haul network.
Consumer DSL services, which include Asynchronous Digital
Subscriber Line (ADSL) and Integrated Services Digital Network
(ISDN) among several others, first were marketed to businesses. Only
after the advent of the personal computer and subscriber demand for
faster data transfer arose was ISDN marketed to last-mile residential and
Small business customers.
ADSL services enable the simultaneous delivery of voice and
data services over standard telephone lines. In addition, it allows multiple
users to share a single voice-and-data connection. Variations of ADSL
(e.g., ADSL 2 and ADSL 2+) can achieve data rates of as much as 20
Mb/s, depending upon a number of factors, not the least of which is the
quality of the copper telephone wires.
ADSL offers asynchronous data transfer, which means that the
Service allows inbound data to move faster than outbound data. Put an-
other way, it means that you can open web pages faster than you can
send files.
ADSL is a hybrid service that combines traditional telecommu-
nications with digital data transfer. The ADSL service relies on two mo-
dems at either end of the local loop. The modem converts the user’s
Voice and data into digital signals, which then are transmitted across both
lines (multiplexing) and encoded as Asynchronous Transfer Mode
(ATM) packets for transmission over a digital network. When the sub-
scriber is receiving data, the modem at the central office decodes the in-
bound data from the ATM network and sends it to the subscriber’s mo-
dem for re-conversion to useable information.
ADSL is relatively inexpensive and allows a faster data transfer
rate than analog modems do. ADSL can provide voice and data services
without major infrastructure changes in the network and enables
Workgroups to share a single voice and data connection.
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The quality and maximum data transfer rate of ADSL services
depend upon the quality of the copper lines, both at the subscriber’s end
and at the central office. Like traditional voice services, ADSL services
are limited by the subscriber’s distance to the central office. ADSL serv-
ices may not be available in all areas or its maximum speed may be lim-
ited significantly.
INTEGRATED SERVICES DIGITAL (ISDN) NETWORK
ISDN is another popular digital telecommunications service that
can deliver both voice and data. Unlike ADSL, ISDN is not delivered
over traditional copper phone wiring. Because it uses a different trans-
mission medium, ISDN offers some distinct advantages over ADSL.
An ISDN line is divided into 24 channels, only 23 of which are
used for data transfer. The 24th channel is reserved for signaling and call
control. Each channel has a maximum symmetrical data rate of 64 Kb/s.
ISDN operates as a full-duplex service, meaning that the upload and
download data rates are the same. Symmetrical data transfer is helpful
for users who produce data and send it to other users via the network.
ISDN services typically are delivered (or “provisioned”) in one
of two ways: as Basic Rate ISDN (BRI) or Primary Rate ISDN (PRI).
BRI services offer two data channels (called bearer channels or B-
channels) and one 16Kb/s control channel (also called a delta channel or
a D-channel).
BRI service offers a maximum data throughput of 128 Kb/s. If
the service is used for both voice and data, an incoming or outgoing call
will drop the maximum data transfer rate to 64 Kb/s. PRI offers 23 64
Kb/s B-channels and one 64 Kb/s D-channel. When provisioned exclu-
sively as a PRI data service, ISDN offers a maximum data transfer rate of
1.472 Mb/s. When provisioned exclusively as a PRI voice service, the
ISDN line can handle a maximum of 23 simultaneous voice calls.
An ISDN line does not have to be an “all or nothing” proposi-
tion. A carrier can provision just a few channels on a PRI for voice serv-
ice, data service or a combination of voice and data services. Unneeded
channels may be left dark. Normally, when PRI service is fractionalized,
the customer indicates the number of channels that should be dedicated
to voice service and the number of channels that should be dedicated to
data service. Unless you are using the entire line, carriers will not provi-
sion an odd number of channels for either voice or data service. They
also may impose minimum requirements for provisioning a line.
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Using this approach, a set number of inbound and outbound lines
can be used to support a private branch exchange (PBX) system rather
than paying for a larger number of individual phone lines that are con-
nected to the PSTN. This arrangement saves the trouble of receiving and
paying multiple individual telephone bills each month. ISDN lines also
may be used to provide dedicated long-distance or toll-free calling serv-
1CCS.
Normally, the cost of an ISDN service includes both a fixed
monthly charge, as well as a charge for actual usage, based on the num-
ber of calls. Some ISDN subscribers use the service to maintain a con-
tinuous data connection between office locations or to their Internet serv-
ice provider (ISP). A single call may last for months. In that ISDN serv-
ices are billed on a per-call basis, this strategy may have no appreciable
impact on the cost of the service. Line quality issues may cause a call to
drop repeatedly, however. This problem generates additional expense on
the subscriber’s monthly bill. Tariffed services provided over ISDN also
are subjected to federal and state taxes, mandatory surcharges (like E911
services) and fees.
ISDN services are flexible and can support larger businesses and
multiple users. The provisioning is flexible in that service can be added
without the need for additional on-site installation. One disadvantage of
ISDN services is that the subscriber may have to sign a contract that con-
tains stiff disconnection penalties if the service is discontinued before the
contract expires. Normally, the carrier does not charge a penalty if the
provisioning is improved, but may add a one-time charge for reconfigur-
ing the service.
T1 SERVICES
T1 services are similar to ISDN services. As with an ISDN line,
a T1 line is divided into 24 channels (Hioke, 1990). Unlike an ISDN line,
a T1 line does not devote an entire channel to signaling. Instead, the con-
trol signals on a T1 line are embedded in the data stream. The maximum
data throughput of a T1 line is 1.544 Mb/s.
Like ISDN lines, T1 lines can carry voice, data or both. TT lines
can be provisioned fractionally to deliver a lower data transfer rate. Re-
maining channels can be provisioned for voice service or left unused. If
the T1 line is used for data, the subscriber will pay a fixed monthly
charge. If the T1 line is used for voice, the subscriber will pay a monthly
charge for the line(s) and additional use charges for tariffed services.
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Tl service can be provisioned over copper, fiber-optic cable or
less commonly, microwave. Tl service is a last-mile service, whether it
is provisioned for voice or data. Unlike standard PSTN service, a T1 is
considered a private line because it creates a permanently open, dedi-
cated circuit to the carrier’s network. Once data have been delivered to
the carrier, they are routed appropriately to the carrier’s voice or data
networks, to a private data network or an ISP.
In the same way that multiple channels of a T1 can be used for
voice or data service, multiple T1S can be used to expand the size of an
organization’s connection to its data provider or to expand the number of
inbound and outbound telephone lines. After a certain point, it becomes
more cost effective for extremely large organizations, like colleges, uni-
versities and large corporations to use a T3 line instead. A T3 line offers
45 Mb/s of data throughput. *
Like ISDN services, T1 services are provided under contract.
The carrier may provide discounts on the cost of the line if the subscriber
is willing to sign a multi-year contract, but stiff disconnection penalties may
apply if the subscriber discontinues the service before the contract is complete.
IP NETWORKING
Internet Protocol (IP) networking was developed in the 1960s
and 1970s (Halabi, 1997). At that time, the Department of Defense
(DOD) perceived critical weaknesses in the PSTN. The weaknesses were
so significant that the DOD wanted a secure communications mechanism
available if the PSTN ever became unavailable due to a national crisis or
a nuclear attack.
IP was designed for the DOD, but it can support a wide variety
of communication applications. It provides a set of standard rules for
network-to-network communications. IP networking is called an unreli-
able service because it does not verify that another party is prepared to
receive the messages it carries. The term best effort often is used in con-
junction with IP networking.
IP can manage multiple routes and intermittent network avail-
ability (Hunt, 1992). IP also addressed thornier issues like the relative
privacy of privileged communication. Copper-based telephone systems
are vulnerable to undetectable eavesdropping at several points in the
transmission circuit. An IP-based network is less vulnerable to eaves-
dropping because it does not create circuits like the telephone network
does.
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In some respects, the basic model of IP networking borrows
heavily from the circuit-switched networking model. The end user has a
station (or device) that attaches to the network. Each network device has
a unique address, known as an IP address. The IP address consists of four
“octets” of three digit numbers. The term “octet” refers to the eight bi-
nary digits required to make one three-digit number. A typical address
looks like the following: 192.168.1.25 (Graham, 1997).
Like numbers in the PSTN, the IP address refers, in part, to the
network to which the device is attached. The remaining address informa-
tion uniquely identifies the device. With these two pieces of information,
devices can attach to and interact with other devices on other networks.
Certain organizations, like the Internet Corporation for Assigned
Names and Numbers (ICANN), the Internet Assigned Numbers Author-
ity (IANA) and regional Internet registries govern the assignment of IP
addresses to networks, the development of top-level domains (like .com
and .org), domain names to individuals and entities, and the searching
mechanisms that make the Internet globally interoperable. These non-
profit entities operate for the mutual benefit of everyone that uses the
Internet and ensure that network operators and domain operators comply
with Internet naming, addressing and routing rules.
When it comes to the Internet, IP networking is only part of the
story. Ultimately communication has to be reliable if it is to be under-
stood. By design, IP is not reliable. A second communications protocol,
known as Transmission Control Protocol (TCP) is used with IP because
TCP is reliable (Graham, 1997).
A TCP packet can be likened to a highly confidential letter in
that the intended recipient must sign for it. A TCP message is divided
into many small packets, which are numbered individually and addressed
to the recipient. The packets also are equipped with a simple self-destruct
mechanism, in case something goes wrong.
The sender (in this case, an application) knows where the pack-
ets should go and who should sign for them, but does not know its way
around town. The application prepares some initial packets, hoping to
find a qualified conversation partner on the receiving end and hands the
packets off to a knowledgeable courier (IP). Because IP is a network
routing expert, it may be able to find several different routes to the desti-
nation (Hunt, 1992). If one route is closed for construction or is experi-
encing a traffic jam, the courier can take a different route. If IP cannot
find any routes, a companion protocol has a limited ability to report this.
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If ordered to do so by the sender, IP can take each packet along
the same route. In most cases, however, IP will take whichever route is
the fastest. If IP makes a bad choice of route, or the route fails after IP
already has selected it, the packet will get lost. If the route failure itself
does not destroy the packet, the self-destruct mechanism will kick in and
terminate the packet automatically.
Because the packets are numbered, they do not have to arrive in
the same order they were sent. Once the packet stream starts to arrive,
TCP on the recipient’s side will send messages back to the originator
(using IP) to let it know that packets have started showing up. TCP on
each side then acknowledges each packet and even acknowledges the
acknowledgments! The recipient TCP will put the packets in the right
order and the originator TCP will generate replacement packets for those
that have been destroyed. *
This stream of acknowledgments and the sending and resending
of packets is what makes TCP a reliable protocol. In the best scenario,
all of the packets eventually show up and the requested services are pro-
vided. Some services, however, are time-sensitive. The packets have to
show up reliably or the service will not work. VoIP and streaming video
are two examples of this type of traffic.
PACKET-SWITCHED NETWORKING
TCP and IP are two components of the larger story of packet-
switched networking. Unlike circuits in the PSTN, data can travel over a
variety of pathways to get to their destinations. Protocols like IP and
other more robust routing protocols instantly can discover new routes
and evaluate which pathways will work best for the data they carry.
Multiple networks converge at many different interchange
points. Should one interchange point fail, routing protocols find other
available interchanges. Failures may slow data transfer, but rarely do
they have more than a temporary impact on data movement.
The distinction between circuit switching and packet switching is
fundamental. In one case, the network path must be absolute, reliable and
dedicated for the data to move. In the other case, the route is almost (but
not quite) irrelevant because many routes can get the information to
where it is going and different data streams can use the same route simul-
taneously.
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Route redundancy is one of the primary advantages of Internet
networking (Halabi, 1997). By ensuring that the national data network
neither is owned nor controlled by one organization or reliant on a single
technology, major network providers can build highly capable, redundant
data routes and interchange points. While data providers may not be able
to anticipate disastrous circumstances, highly redundant network archi-
tecture is well prepared to accommodate them.
The ability to make the network infrastructure available to any
user at any time also is a significant advantage. The common highway
approach to network infrastructure not only reduces its operating cost,
but also controls the cost of and need for the future improvements neces-
Sary to ensure adequate network capacity.
IP networking is not without its faults. The issue of reliability is
significant because businesses are reluctant to rely on technology that
they perceive as unreliable or unable to deliver a consistent user experi-
ence. Client-server applications are used heavily on the Internet and
other IP networks to address the need for reliable communications across
an unreliable network.
Packet loss is a major disadvantage of IP networking. Not all ap-
plications are sensitive to packet loss; TCP was designed to deal with the
retransmission of lost or damaged packets. At the same time, packet loss
and retransmission cause an apparent reduction in the data transfer rate
of an affected application.
Some services are simply intolerant of network faults like sig-
nificant packet loss and latency. Time-sensitive applications like VoIP
may require significant accommodation on the part of the user or the
Service provider to ensure that loss-sensitive and time-sensitive applications
receive the highest possible routing priorities as they traverse the network.
Security also is a disadvantage on an IP network. Many of the
basic protocols in heavy use on the Internet today were designed in the
1960s, a time during which the network security needs of 2011 could not
have been anticipated. While users always must be on guard against at-
tacks to their personal devices and domains, network operators also must
be vigilant against directed and undirected attacks against their network
facilities. Distributed denial-of-service attacks, designed to overwhelm a
single target, hacks designed to breach security or interfere with Internet
routing to or from particular sites, and proof-of-concept attacks are near-
daily occurrences.
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COMPARING PSTN SERVICES TO INTERNET
BROADBAND OPTIONS
While the PSTN offers many voice and data transmission op-
tions, IP networking – also known as broadband networking – has
opened the door to even more options delivered across other media. Most
notably, cable television providers have carved out a significant segment
of the broadband Internet market.
Cable Modems
Cable television systems ideally are suited to deliver high-speed
voice and data services to end-users (Franklin, 2011). Their copper and
fiber infrastructure has the capacity to deliver data with only reasonable
modifications to the network. Because of the way television signals are
multiplexed (combined) onto the copper infrastructure, operators effec-
tively can assign channels to data upload and download. A cable modem
at the user’s end encodes outbound data and decodes inbound data.
Cable data service is relatively inexpensive, compared to some
other data services. Multiple stations on the local network can use a sin-
gle cable modem. More channel space on the cable operator’s network is
devoted to download than upload, which means that cable modem users
can receive data much faster than they can send it out.
Unlike a dedicated data line from a telecommunications carrier, a
cable operator’s IP network resources are shared among all of its users.
When a large number of users attach to the network simultaneously, the
overall ability of data to move through the network may slow noticeably.
For casual users, this may be more of an annoyance than a true problem.
For business users, however, having reliable, dedicated Internet service
may be worth the additional cost, especially for applications like VoIP.
Cable network operators typically do not provide service level
agreements to their lowest-tier users. Business class users who pay addi-
tional monthly premiums may receive better service guarantees, dedi-
cated upload and download data transfer rates, and prompt repair serv-
ices when problems arise.
U-Verse
U-Verse is a combined voice, data and content service offered by
AT&T. U-Verse is an IPTV service, provisioned over standard voice-
grade telephone lines and offers a feature-rich IP-based telephone service
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that can accommodate multiple lines, television channels and Internet
data packages that provide up to 12 Mb/s of data download.
U-Verse is designed to be a residential service; however, it may
be appropriate for home-office use. Service levels and repair times are
not guaranteed. Like cable modems, the provider delivers a shared net-
work environment. When a large number of users join the network, per-
formance may drop.
FiOS
Verizon offers a fiber-optic service (FiOS) that delivers high-
speed Internet, television and Voice services to residential and business
customers in certain states (http://en.wikipedia.org/wiki/Verizon FiOS).
Verizon has suspended expansion of its FiOS network build-out indefi-
nitely in states where no deployment has occurred. The company an-
nounced that it would continue to build its fiber network in states with
existing FiOS deployments.
Subscribers can elect traditional telephone service or VoIP serv-
ice with a FiOS connection. Voice, video and content data are delivered
using distinct infrared light wavelengths. Maximum data download vary
across four subscription tiers, but Verizon offers either a symmetrical or
asymmetrical service in the middle tiers. The top and bottom tiers are
asymmetrical only.
The lowest tier provides a data transfer rate of 5 Mb/s down and
2 Mb/s up at about $75/month. The highest tier is provisioned at 150 Mb/s
down and 35 Mb/s up, and is priced at about $200 monthly (Verizon, 2011).
One disadvantage of FiOS is that the service is powered at the
subscriber site. If the power fails, the service – including phone service –
will not work.
VoIP
VoIP is an IP-based data application that enables users to place
Voice calls through a packet-switched data network instead of through
the circuit-switched PSTN (FCC, 2011). A primary attraction of VoIP is
the ability to eliminate comparatively expensive telephone lines supplied
by a traditional telecommunications carrier. VoIP also may be used as a
Substitute for long-distance telephone services.
Even a small business may have several telephone lines. If the
business owner chooses to receive telephone service directly from the
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carrier, each line will be billed separately and may or may not have simi-
lar numbers.
To simplify billing and interoffice communications, organiza-
tions may use a private branch exchange (PBX) to allow several handsets
to share a smaller number of telephone lines. This approach will require
a PBX and specialized handsets and wiring in the office. Certain office
equipment – like fax machines, data terminals or credit card terminals –
each may require a dedicated analog phone line. This equipment cannot
be served by a PBX system. Separate lines must be maintained for these
devices.
Most modern offices have an Internet connection of some type.
A VoIP server can use an appropriately provisioned Internet connection
to provide voice services. The VoIP server would replace individual
telephone lines or a PBX, with the exception of those devices that require
a dedicated analog line. Some VoIP systems require special VoIP hand-
sets. Other systems can use existing handsets and attach to the data net-
work through a special adapter.
In theory, VoIP services can traverse any type of IP network.
Realistically, VoIP needs a stable, reliable consistent Internet connection
to work properly. If you choose to use a VoIP service, better results will
be found from a symmetrical data service that offers dedicated data
transfer rates than from a service that offers asymmetrical data transfer
rates and does not guarantee its service levels.
Low-cost VoIP providers like Vonage will operate on any IP
network. These services appeal mainly to residential customers who do
not need multiple lines and do not want to pay monthly fees for a land-
line telephone or for long-distance charges.
The subscriber connects a standard telephone to the Vonage FXS
voice gateway. The VoIP gateway also is connected to the subscriber’s
LAN. Voice data is sent to Vonage via the gateway and Vonage hands
the call off to the PSTN. Once on the PSTN, the call is routed to the re-
cipient.
More robust VoIP solutions work in a similar fashion. Special
VoIP handsets called Session Initiated Protocol (SIP) phones may be
connected to the subscriber’s LAN or to a voice-only data network and
send data to a VoIP server. Technically, SIP is a protocol that controls
the way VoIP telephone calls are set up and closed down, but SIP also
plays a role in instant messaging (IM) and instant notification services.
When used in the context of a VoIP phone system, the VoIP server
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passes the data from the SIP phone to a VoIP service provider. The service
provider transfers the call to the PSTN where it is routed to the recipient.
The VoIP server, in conjunction with the SIP handsets, enables
many functions that would not be possible using standard phone or a
PBX system; these functions could be possible only at significant added
expense. Some services the VoIP server can perform include:
1. Auto-answer and menu-driven call routing;
2. Extension-specific voicemail; voicemail to email no-
tification;
Music-on-hold;
Night service;
Multi-line conferencing;
User-defined hunt groups and extension groups;
All history;
Call reporting;
9. Scheduled out-of-office messages;
10. Queuing;
11. All logs and reporting;
12. Paging and intercom services; and
13. Other specialized functions.
i
SIP handsets also can enable staff to move around the office or between
offices. A user simply “logs in" to a SIP phone and all calls to the user
are routed there, no matter where the user is located. This flexibility can
be helpful for specialized personnel who may circulate between offices.
A primary advantage of using a VoIP server to provide phone
Service is the re-use of the existing data network. In that phones can plug
into the data network, no new wiring is needed. The VoIP server acts as a
gateway to the PSTN and new lines can be added as needed.
Once the phone is integrated into the data network, the user can
log into the VoIP server from anywhere, not just from the physical office
space. This integration enables the user to make business calls from
home or cover on-call duties while giving the appearance of being in the
office. Calls dialed into the office number can be routed to wherever the
user is logged in. Outbound calls enter the PSTN with the caller ID in-
formation of the main office.
VoIP can be used to facilitate inter-office communications as
well. With two office locations, it is possible to set up a VoIP server in
each office and connect both locations using the Internet. If calls between
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the offices are normally toll calls, using the VoIP servers to carry these
calls between the offices will eliminate this extra expenditure.
The VoIP servers also are configured to recognize their local ex-
changes and can perform VoIP trunking. Trunking is the transport of call
data from one intermediate point to another. If Office A needs to place a
call that normally is a toll call, but from Office B would be a local call,
the VoIP server in Office A will hand the call to the VoIP server in Of-
fice B. The Office B VoIP server then will place the call as a local call,
saving toll charges that otherwise would have been incurred by Office A.
Introducing two VoIP servers to a local network not only may
help avoid toll call charges, but also may introduce two failure points
into the network. Another option may involve using a single VoIP server
that knows the location of all stations on the network. When a call comes
inbound from the PSTN, the VoIP server can identify the intended desti-
nation and direct the call to the correct location, based upon the incoming
area code and exchange number or NPA-NXX combination.
Considerations for Migrating to VoIP
VoIP is a time-sensitive service, which means that it is suscepti-
ble especially to transmission impairments like latency, jitter and loss
(Thompson, 2011). In traditional telecommunications, latency is the
product of an extreme distance between the sender and the receiver. Tim-
ing delays introduced by switches impede the ability of the parties to
have a normal conversation. The speaker finishes talking well before the
listener finishes hearing what is being said. The result is an uncomfort-
able delay between verbal exchanges.
Latency can affect VoIP communications as well, but it gener-
ally is not distance related. Instead, lost packets and excessive retrans-
missions delay a VoIP application’s ability to reorder and process TCP
packets. The result is latency introduced into the conversation.
Jitter is another transmission impairment that typically occurs
when too many packets are dropped. Dropped packets can be the result
of poor line quality or excessive network congestion. VoIP applications
can live with some level of packet loss. When packet loss becomes too
great, however, the quality of the call drops perceptibly. Jitter can intro-
duce echo, dropouts, distortion and attenuation into the call data and in
severe cases, render the call unintelligible.
Latency also can be introduced when packets move between
provider networks. Providers have a great deal of control over what hap-
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pens inside their networks, but may have much less control over what
happens at the interconnection point, where data moves from one pro-
vider’s network to another. Any number of issues may prevent data from
being handed off cleanly. Data may have to travel significant distances to
reach an interconnection point, especially if providers have not estab-
lished peering relationships with each other. Peering is an agreement
between providers to exchange data at a mutually convenient informal
exchange point. It is essentially an agreed-upon shortcut.
Data interchanges also can be problematic because one provider
may recognize and give priority to time-sensitive traffic, while,another
provider may not. One provider may have excess capacity, but the hand-
off network may be congested chronically. A provider may have inher-
ited network infrastructure as the result of a merger or acquisition, and
the inherited infrastructure may not yet be compliant fully with the new
owner’s routing policies and procedures. Parts of a provider network may
have older, less reliable or less capable routing equipment still in service.
All of these issues are easy to resolve from a technical perspec-
tive, but in practical terms, it can be difficult to isolate and correct net-
work issues, even when working with the most patient and dedicated
network engineers. The result of any of these conditions can be unsatis-
factory VoIP performance with no apparent resolution.
If you have multiple offices and intend to connect them using
VoIP, one way to avoid network handoff problems is to use the same
Internet provider at all locations whenever you have the opportunity to
do so. By using a single provider, you eliminate the handoff as a source
of delay. You also may get more consistent technical support when the
network engineer assigned to the problem has control over the entire
network path.
E-911 services can be problematic for a VoIP implementation. If
you plan to migrate to a VoIP environment, you must take steps to ensure
that you have reliable access to 911 services at all locations (FCC, 2005).
In a VoIP system, E-911 data transmitted to a call center may be incor-
rect and potentially could re-route first responders to the wrong physical
location. For this reason, it is important to maintain at least one analog
phone line along with your VoIP system at all times. Outbound calls to
emergency responders must be placed on the analog line. The analog line
must be identified clearly as an emergency phone and all office person-
nel should be instructed to use the designated line for emergency assis-
tance calls.
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An analog line or traditional phone line may be used for other
devices like your fax machine or credit card terminal, and pull double
duty as the 911 line, but all personnel should trained in case of an emer-
gency to use this line instead of the VoIP phone system to invoke 91 |
services properly.
Business continuity is an important consideration for VoIP in-
stallations. If you migrate to VoIP, your VoIP server should be protected
by an uninterruptible power supply (UPS). The UPS should have enough
capacity to run your phone system for at least a short period of time. This
will help ensure that your phone system continues to work during brief
Outages.
Security is another important consideration for your VoIP instal-
lation (Kuhn et al., 2005; Plewes, 2011). A VoIP server is a juicy target
for hackers who may be looking for outbound calling capabilities. If you
manage and maintain your own VoIP server, protect your server’s ad-
ministrative functions with a strong password. Strong passwords are
those that: do not contain any recognizable words in any language; in-
corporate upper and lowercase letters, numbers and non-alphanumeric
characters like # or l; and have between eight and sixteen characters.
Change your password regularly.
Consider disabling remote administration capabilities on your
VoIP server. This disabling may cause some inconvenience because it
will require the administrator to be present physically at the VoIP server
to make configuration changes, but it also will prevent remote attackers
from gaining administrative access to your VoIP server.
Implementing VoIP
There are several turnkey VoIP solutions to be considered. If you
have the time and interest in setting up your own VoIP server(s), one
open-source implementation is called Asterisk. Some business owners
are nervous about the term open source, a term that conjures up images
of legions of Volunteer programmers who create applications that are
supported only marginally, if at all. With no one taking ownerships of the
process, who will be around to fix something that goes wrong? Many
businesses are left with the impression that using open source software is
tantamount to going out on a dangerous limb.
In reality, open source means that the programming code is
available freely to anyone who wants to view, modify or use it. There is no
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Engilman
cost to download an open-source application. There are plenty of organi-
zations that are dedicated to providing full-service support to open-
Source applications like Asterisk.
In a way, the open-source approach fundamentally is better than
a proprietary approach. In a proprietary approach, no one but the owner
can look at the source code. Users have no way to know what the weak-
nesses are and have no way to fix or customize an application for their
use. Not knowing how something works is one thing; not being allowed
to look at it – especially when your business may depend on it — could be
something different.
Asterisk
Asterisk is a scalable, open-source IP-based PBX solution that
can be used for businesses of any size. Asterisk enjoys the support of a
large community of users and developers who are invested in the success
of the product. If you want to run your own VoIP server, you can down-
load the product, install it and have a working VoIP server in less than 30
minutes. You can find more information about Asterisk, including
documentation and help, at http://www.asterisk.org.
One popular Asterisk-based implementation is called Trixbox
Community Edition or Trixbox CE. New and prospective new users
download this product at a rate of about 65,000 per month. The popular-
ity of Trixbox is due to the ease of setting up and maintenance through a
web-base graphical interface. Additionally, Trixbox distribution has a
robust number of applications that extend the base Asterisk platform.
Trixbox CE has been available since 2004. Fonality, the company that
supports the Trixbox CE distribution, offers other products and services
to complement its Trixbox CE line. More information about Trixbox CE
can be found at http://fonality.com/trixbox/.
If having a VoIP server is appealing, but the prospect of manag-
ing and maintaining it is not, providers are available who are willing to
host a VoIP solution for your business. A hosted solution allows you to
take advantage of VoIP without requiring you to spend additional time
and effort on managing, maintaining and securing your VoIP server(s). You
will pay a regular monthly fee for the service, but may find that a hosted
VoIP solution offers a nice compromise between the cost-saving and
time expenditure that may be required to set up, manage and support
your own phone system.
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A Telecommunications Primer
BEYOND VoIP SERVICES
VoIP is just one component of the network in a modern practice.
A practitioner with multiple offices, a working Web server, databases for
billing and business recordkeeping, electronic patient records, desktop
applications and other network devices that generate a stream of data has
made a significant investment in his/her business. The safety of these
business records is paramount. Assuring smooth data transfer between
offices to support VoIP and other networked services also is important.
A host of new services designed to create sophisticated, secure
and capable networks for small- and medium-sized businesses has
emerged, and smart practitioners will consider these services as a way to
protect their business operations.
One such service is Multi-Protocol Label Switching (MPLS).
MPLS services, which are available through telecommunications carri-
ers, can create a private Wide Area Network (WAN) that connects each
office to the WAN (Fischer, 2007). Combine this high-impact data trans-
port service with secure hosting for your Web server, VoIP server, data-
bases, patient records, data backup server and other sensitive applica-
tions, and you have reduced the risk of data loss and the loss of opera-
tional capabilities significantly.
With a hosting solution, the support and maintenance responsi-
bilities for each server can be handed off to the hosting provider. The
data owner also can choose to manage and maintain the servers. Hosting
takes place in a secure data center that is monitored 24/7. All servers in
the data center are backed up and replicated at other data centers in re-
mote locations. If something were to happen at one data center, the data
still are preserved and completely accessible elsewhere.
The network connections in the data center are significantly
larger than necessary, so data bottlenecks do not occur. Your business
continues to operate as it did when your servers were located in an office,
but your connectivity and security are improved significantly. With your
business records stored safely in a data center, potential disasters like
water leaks, fires and break-ins will have little to no impact on your ad-
ministrative functions.
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Engilman
CONCLUSIONS
VoIP offers several significant benefits over traditional tele-
communications services. It can be combined with traditional telecom-
munications service and IP networking services to deliver information
technology (IT) support to the modern practice and to enable practices to
adopt IT-enhanced business models.
Migration to VoIP is not without risk, but the risks can be miti-
gated by understanding the functional differences between traditional
telecommunications and IP-based services. By understanding how tele-
communications services can work together, practitioners can build an IT
infrastructure that supports its current and future communications, net-
Working and business needs.
REFERENCES
Bigelow J. Understanding Telephone Electronics. Carmel, IN: Prentice-
Hall 1992.
Federal Communications Commission. http://www.fcc.gov/cgb/con
Sumerfacts/voip911.pdf (2005).
Federal Communications Commission. http://www.fcc.gov/voip/ (March
15, 2011).
Fischer T. MPLS Security Overview: An IRM Research White Paper.
London, England: Information Risk Management 2007.
Franklin C. http://computer.howstuffworks.com/cable-modem.htm
(March 15, 2011).
Graham B. TCP/IP Addressing: Designing and Optimizing Your IP Ad-
dressing Scheme. Boston, MA: Academic Press 1997.
Halabi B. Internet Routing Architecture. Indianapolis, IN; Cisco Press 1997.
Hioki W. Telecommunications. Englewood Cliffs, NJ: Prentice-Hall 1990.
Hunt C. TCP/IP Network Administration. Sebastopol; O'Reilly and As-
Sociates 1992.
101
A Telecommunications Primer
Kuhn DR, Walsh TJ, Fries S. Security considerations for voice-over IP
systems: Special publication National Institute of Standards and
Technology. US Department of Commerce 2005:800-858.
Plewes A. http://www.silicon.com/special-features/voip-security/2007/
03/09/voip-threats-to-watch-out-for-39166244/(March 15, 2011).
Thompson J. http://www.voip-info.org/wiki/view/QoS (March 15, 2011).
Verizon. http://smallbusiness. Verizon.com/products/internet/fios/over
view.aspx?Foverview (March 15, 2011).
WEB RESOURCES
http://en.wikipedia.org/wiki/Verizon FiOS
http://localcallingguide.com *
http://www.icann.org/
http://www.iana.org/
http://www.asterisk.org
http://fonality.com/trixbox/
GLOSSARY OF TERMS AND ACRONYMS
ADSL: Asynchronous Digital Subscriber Line. A digital telecommunica-
tions service delivered over standard copper wiring.
ARPANet: Forerunner of the modern Internet.
Asterisk: An open-source Voice-over IP (VoIP) distribution.
Asymmetrical: Data networking service configuration that provides une-
qual inbound and outbound data transfer rates.
BRI: Basic Rate ISDN. An ISDN service configuration that provides two
64 Kb/s data channels and one 16 Kb/s control channel.
Broadband: A method of transferring data that features high data transfer
rates and allows multiple users to access the same network transit re-
sources simultaneously.
Cable Modem: A device used by cable television providers to decode
video data for the subscriber and provide two-way encoding and de-
coding of voice and data services.
Central Office: The subscriber's entry point into the Public Switched
Telephone Network's (PSTN) switching hierarchy.
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Engilman
Circuit-switched Network: A telecommunications network that creates
ad hoc end-to-end temporary circuits to facilitate communication.
Download: The reception of data from another source.
DSL: Digital Subscriber Line. A generic term that describes a family of
digital communications services, primarily delivered over standard
copper telephone wires.
FIOS: Fiber optic service. A branded fiber-to-the-premises service of
fered by Verizon in several U.S. states.
Hop: In-Internet routing, one leg of a data pathway.
ISDN: Integrated Services Digital Network. A digital telecommunica-
tions service that can be delivered over copper wiring.
IP Network: A network based on the Internet protocol.
ISP: Internet Service Provider. A business entity that provides end users
with transport access to the Internet.
Last Mile: The copper wiring that runs between the telephone company's
central office and the subscriber's premises.
LATA: Local Access and Transport Area. A service area definition es-
tablished when AT&T was divested of its regional Bell operating
companies that indicated where and by which provider’s telecommu-
nications services could be offered.
Latency: An unacceptable delay between the sender and receiver on a
communication channel. Latency can be caused by distance or poor
line quality.
MPLS: Multi-protocol Label Switching. An efficient method of routing
data through a wide area network.
Packet: A piece of information that can be routed through a network.
Packet Loss: A circumstance where information that is being routed
through a network is damaged or destroyed during transit.
Packet-switched Network: A method of transferring data that provides
for multiple data pathways to a single destination.
PBX: Private Branch Exchange. A telephone switch that serves a private
business or a single entity and enables the sharing of inbound and out-
bound telephone lines.
PRI: Primary Rate ISDN. A digital telecommunications service that pro-
vides 23 channels in a single carrier, which can be configured to de-
liver voice, data or both.
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A Telecommunications Primer
PSTN. Public Switched Telephone Network.
Service Level Agreement: An agreement by a service provider to deliver
a specified set of services, including repair times, usually on a con-
tractual basis.
SIP: Session Initiated Protocol. A VoIP protocol that provides call setup
and teardown standards.
Soft Phone: A software application that provides handset services to a
computer or other mobile device.
Station: The end-user's telephone.
Symmetrical: Data networking service configuration that provides equal
inbound and outbound data transfer rates.
Upload: The transfer of data from a source to a destination.
VoIP: Voice-over Internet Protocol. An application that provides for the
transport of voice data across a packet-switched network.
VoIP Server: A device that encodes voice data for transmission over a
packet-switched network.
104
CLOUD COMPUTING IN DENTISTRY
Lynn A. Johnson
ABSTRACT
We now use computers that access software and information around the world
through wired and wireless networks. This combination of global servers and
networks is known as the cloud. This chapter: (1) describes how computing has
evolved to the current state of cloud computing; (2) summarizes how cloud
computing supports oral health care; and finally (3) summarizes a few of the
most popular cloud-computing tools.
Computers have evolved physically as well as functionally – how they
operate and communicate. Computing started with mainframe computers that fill
a room. Now that same computing power can be held in the palm of your hand.
Concurrently, the software that operates computers has evolved from clunky
text-based commands that only a few highly skilled programmers knew to soft-
ware that can be controlled by the touch of a finger. Originally individual com-
puters stored the software and data the users created; now this same information
is stored on servers around the world. Lastly, computers now use a combination
of wired and wireless networks to communicate and share information.
The cloud removes the burden of routine IT operations from the clini-
cian. Back-ups, software upgrades, HIPAA security, Scanning for viruses and
other tasks for which dentists are not trained specifically, are performed auto-
matically and at a lower cost. In addition, patient information can be accessed
securely and from multiple devices. A subscription is purchased for cloud soft-
ware and is known as Software as a Service (SaaS). A significant benefit of
cloud patient information systems is that they remove the burden of the physical
and technical HIPAA security requirements for a practice’s patient information
for the system.
Cloud services also include office functions such as file sharing, sched-
uling and voice communication.
KEY WORDS: cloud computing, software as a service (SaaS), security, network-
ing, cloud computing in dentistry
105
Cloud Computing
WHAT IS CLOUD COMPUTING2
Cloud computing is a difficult concept to explain. The term itself
avoids all sensibilities. You cannot see, touch, smell, hear or taste the
cloud. The basic concept behind the cloud is that all of your media is
stored on the Internet so that you can access it from any device, any-
where and at any time. This concept is such a significant change in how
we use technology that cloud computing will be explained in three dif-
ferent ways – by describing the evolution of computing, how cloud com-
puting works and reasons to use the cloud.
Evolution of Computing
Computing has evolved in ways few could predict. A short
summary of two characteristics of computing evolution will demonstrate
the magnitude of this change – where software is located and how you
communicate with colleagues.
Mainframe Computing
In the early days of computing, mainframes were physically
massive computers that contained all the software you required as well as
the data you created using that software (Figs. 1-2). You interacted with
the mainframe by using a terminal (display and keyboard only, no mouse
or other peripheral) that was connected using a wire to the mainframe
computer. You could communicate easily with others who used main-
frames via early forms of email.
Personal Computers
Computers eventually became small enough that the individuals
were able to own and control them (Fig. 3). The owner was responsible
personally for loading all software as well as for all operations such as
back-ups (Fig. 4). These computers were not connected and are known as
personal computers (PCs). If you needed to share a file, you copied it to a
floppy disk and physically moved it to a different computer (Fig. 5).
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Johnson
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107
Cloud Computing
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Creative Commons Attribution-Noncommercial-Share Alike. http://www.flickr.
com/photos/hexholden/25113852.2/
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108
Johnson
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up data. Rae Allen, 5.25" floppy disk, October 7, 2007 Creative Commons At-
tribution-Noncommercial. http://www.flickr.com/photos/raeallen/ 1501131768/
INTERNET AND NETWORKED PCs
Wires returned as personal computers became connected via lo-
cal area networks to allow computers to communicate (Fig. 6). This sys-
tem of wires, both within a building and between buildings, is known as
the Internet. The owner of each computer still did the processing on
his/her computer, but files could be shared easily across the wires. The
World Wide Web, a.k.a. the web browser, became the most commonly
used application on a personal computer. Hotmail and Yahoo are a few
Well-known early applications that used the Internet (Fig. 7). Applica-
tions that were located on remote servers and operated over the Internet
locations started to emerge.


109
Cloud Computing
Figure 6. Computers connected to a server on a local area network.
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THE CLOUD
Finally, the wires have disappeared and we now use computeſ:
to communicate over wireless networks. But that is not the end; in addi-
tion to computers, we now use handheld devices such as phones and tab:

















110
Johnson
lets to communicate over these wireless networks in what is now known
as the post-PC era. The lack of wires is a great convenience.
The term cloud really refers to storing information on the Inter-
net that means, in practical terms, you are storing information on a server
owned and operated by another company. The latest evolution of the
cloud is software applications that use a Web browser; not only is your
information stored on the Internet, but so is the software. The Video
Cloud Computing Explained (http//www.youtube.com/watch?v=QJnc
Firhjpg) gives an easy to understand explanation of cloud computing.
How Cloud Computing Works
When you are working in the cloud, the operations you are con-
ducting – whether recording a health history, calculating a bill or com-
municating with a patient – are executed on a server that is located
somewhere unknown to you. That server might be in the next town or
even halfway around the world. It is important to note that any informa-
tion associated with your operation also is stored on a server in an un-
known location.
Having your software located on a remote server in an unknown
location may give you pause at first, but it has a large number of advan-
tages. Consider what is needed to run the patient information software of
a practice. Dentists are highly trained and skilled clinicians. Most clini-
cians are not necessarily information technologists and, thus, usually hire
local IT experts to install and update software and conduct other soft-
Ware- and hardware-related tasks. This means you not only need to de-
cide what software you will use, but you are responsible for the myriad
of tasks associated with it on a day-to-day basis. With the cloud, all op-
erations and data occur on a remote server. Thus, when a computer, lap-
top, tablet or other device dies, you can move to a different device and
still be able to access the information because information stored in the
cloud is automatically backed up. No data are lost and back-ups do not
need to be performed.
When you purchase a cloud service, a number of functions hap-
pen automatically. Upgrades happen automatically – neither you nor
your IT expert needs to install them. Concurrently, you do not need to
Screen for viruses because the company offering the software does this
automatically. Your convenience is increased greatly. You are no longer
constrained to work at a single computer, but rather can work wherever you
111
Cloud Computing
have Internet access. Usually the only software required on that com-
puter is a Web browser, meaning that you can access many of the appli-
cations on not just a computer, but also on mobile devices such as tablet
computers and Smartphones. One word of caution, however: software
that works well using a computer’s Web browser may not be optimized
for the small form factor of a tablet or Smartphone. You may need to
scroll up, down and sideways continuously when uses a Web browser on
the smaller devices.
Software as a Service (SaaS)
If there is one technical term associated with cloud computing
that everyone needs to know, it is Software as a Service (SaaS; pro-
nounced saes). With SaaS, you do not purchase software that needs to be
installed; rather you buy a subscription to the software. Just as you do not
write the articles that are in a magazine, operate the presses that print it
or operate the vehicle that delivers the magazine to your door, you do not
need to install, update, back-up or perform any of the other operations
usually associated with a software system. Instead you pay a single sub-
scription fee, with those operations occurring behind the scenes just like
the creation of the magazine. You usually only need a Web browser to
access the software and it rarely matters if you have a Mac or Windows
computer. So you finally can purchase the computer you want and not
only the one that your software requires.
Security
Security of information is a requirement of all cloud services. An
initial reaction of most dentists is that they can do a better job of securing
their patient information than a company. HIPAA requires anyone who
stores ePHI to fulfill numerous physical and technical requirements. For
example, a practice needs to detail when back-ups are performed, where
offsite back-ups are stored and how media is destroyed. In addition, the
practice must document that the procedures described in the policy are
performed. By using a dental cloud service, the practice is no longer re-
sponsible for writing and documenting many of the HIPAA require-
ments. Instead, the cloud service provider performs the writing, perform-
ing and documenting of many HIPAA requirements. The Health Infor-
mation Technology for Economic and Clinical Health Act (HITECH
Act) – which offers financial incentives for the implementation of elec-
tronic health records (EHR) and broadens the scope of privacy and secu-
rity protections already under HIPAA — has increased the accountability
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Johnson
of HIPAA greatly and significant fines have been levied for violations. It
is anticipated that as the publicity around HITECH grows, more practices
will move their patient information system to the cloud. It also is antici-
pated that clinicians will not want to be burdened with the IT security
requirements of HIPAA and instead pay to have that security provided
for them.
CLOUD COMPUTING AT WORK
Three free or low-cost cloud productivity applications are de-
scribed that can be of use in almost any office setting. It needs to be
noted that free applications usually come with ads.
DropBox for File Sharing
Increasing Volumes of software are being written specifically for
mobile devices (e.g., Dropbox, http://dropbox.com; Fig. 8) that is one of
the most popular cloud applications. Such software can be thought of as
a Web-connected folder on your PC, tablet or Smartphone. Put a file in
your Dropbox folder on your laptop and you can access it on your phone
or any other device with Dropbox. If you make a change to the file, that
change is synchronized across all of your devices connected to Dropbox.
Dropbox works on all major platforms: Windows, Mac, Linux, iOS and
Android.
Doodle for Scheduling
With Doodle, you can “poll” participants about their availability.
Doodle integrates with Facebook and iCal and Google calendars. It
works well for scheduling groups that are on different time schedules or
live in various locations (Fig. 9).
Skype for Voice Communications
Skype is used to make crisp and clear audio and videophone
calls over the Internet. Using your computer you can “call” a colleague
who also has a Skype account on his/her computer. There is no charge
for this service. For a small charge, you can call a cell phone or regular
phone.
CONCLUSIONS
Technology has evolved to the point that we are able to commu-
nicate easily and work wherever we are and whenever we want. We use a
113
Cloud Computing
variety of devices from laptops to phones to share information securely.
The cloud is what makes this possible. It will continue to evolve in ways
that we are not yet able to predict. Like real clouds, the cloud will always
change.
Figure 8. Illustration of Dropbox syncing, sharing and storing files.
Kristi Barrow, Favorite Tech products-File Syncing-Dropbox, Novem-
ber 18, 2009. http://www.kristi-barrow.com/favourite-tech-product-
dropbox-iphone-app/
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Figure 9. Creating a schedule using Doodle.


114
CLOUD COMPUTING
Craig Scholz
ABSTRACT
Cloud computing has been growing across small business over the last few years
at an exponential rate. Its impact on overall cost, accessibility and implementa-
tion has made it appealing to many orthodontists. By hosting data offsite on
large managed data centers, end users can see a significant decrease in overall IT
costs and administration. While there are limitations to cloud computing, its
potential advantages suggest that the Orthodontist consider this approach when
choosing a platform to operate their current and future practice management
technology.
KEY WORDS: technology, practice management, cloud computing
Stop me if you’ve heard this one before ... It is a busy Monday
afternoon in your office when your office manager tells you that your
server is getting error messages because it is running low on drive space.
You immediately contact your IT person (which in many cases is you) to
discuss your options. After exploring these, you decide to purchase a
new server, updated operating system (OS), Sequel Server (SQL) and
backup device with software and antivirus. You find out you also will
need to upgrade the SQL on all your workstations and will need new ver-
sions of several Microsoft products to support the new server. This will
cost you two down days, some additional training and more than
$15,000. You are not happy about any of this, but you almost blow a
gasket when you find out that more than half of this cost is for “soft-
Ware.” You drive home questioning how needing more space on your
hard drive ended up costing you $15,000!
How happy would you be if you never had to go through this
Scenario again? An increasing number of small business owners have
been delighted to leave behind their in-house servers and IT support by
moving to the cloud. So many in fact that Gartner Inc. (one the world's
leading information technology research and advisory companies based
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Cloud Computing
in Stamford, CT: www.gartner.com) predicts more than half of all soft-
ware will reside in the “cloud” by 2014. And while a move to Internet-
based computing is not a panacea, it has enough upside that many ortho-
dontists are tallying up their IT costs and headaches and making the
move. This chapter will discuss the pros and cons of cloud computing
and will inform you concerning some of the primary variables involved
in this widespread transition from in-house servers to true Internet-based
computing.
WHAT IS CLOUD COMPUTING”
There are about as many definitions of cloud computing as there
are orthodontic appliances – but in its basic sense, cloud computing is
location-independent computing, where shared servers provide resources,
software and data on demand. Instead of storing data in your office, data
reside in an offsite facility that serves, maintains, updates and backs up
your files. These services are provided with monthly service fees just like
your Internet and telephone services. In essence, you lease these IT serv-
ices rather than purchasing them. In many ways, cloud computing is a
natural extension of the expanding Internet, with amounts of data ac-
cessed and stored across the globe. Data-hosting facilities house hun-
dreds and even thousands of processors and are certified at increasingly
stringent levels called SAS levels. When IT is outsourced to the cloud,
the end user no longer has to have the expertise to set up and maintain
his/her computer infrastructure.
Cloud computing provides a delivery model of IT services based
on Scalable resources, so it is easy to add storage, users and other fea-
tures. Software generally takes the form of applications the user can ac-
cess through a Web browser or local client, just as if the full system were
installed locally on his/her computer.
Cloud computing actually began in the late 1960s with the ad-
vent of large supercomputers, designed to follow a model much like the
distribution of electricity and other utilities. Instead of purchasing your
own generator to create power when you move into a home, you buy it
from the utility company that produces it in great volume. Similarly, by
centralizing servers and data processing, new levels of efficiency and
optimization are reached in the cloud. Many orthodontists already are
using existing cloud computing applications such as Google, Facebook,
iWork and others (Fig. 1).
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Scholz
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- - Apple iTunes? Amazon.com?
photos videos comments Locker - - o º twº
links to music social games * Netflix? Huluº Spotify:
M O Q 3. T St 3. | ey - ºppºnºsyetºoterºgºmºsºming Sºurce: Company websites
Figure 1. Connectivity = cloud computing. Consumers expect to get their infor-
mation 24/7 from the palm of their hands.
Cloud computing has been growing at exponential rates over the
last several years, with Gartner declaring cloud computing the number-
One new technology for 2010. The Wall Street Journal recently reported
that the cloud computing industry is estimated to reach $42 billion by
2012 – nearly half the entire software business.
Significant changes have occurred over the last several years
With orthodontic computer usage as well. Today’s orthodontists manage
all kinds of patient data and their patients and referrals increasingly de-
mand access to these data as well. It is not uncommon for an orthodontic
office to require access to management data, 2D and 3D imaging, elec-
tronic treatment records, appointment confirmation and online patient
access - all from multiple locations. Many doctors, patients and referrers
also increasingly need this information on mobile devices as well; these
devices are burgeoning with social networking applications such as
Facebook and Twitter. Cloud computing dramatically opens up the avail-
ability to all this data.
BENEFITS OF THE CLOUD
The main driving force toward cloud adoption is the same across
all business, namely decreased costs and greater efficiencies. By outsourc-

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Cloud Computing
ing servers, software licensing and other expensive IT to a data center,
businesses can decrease their bottom line and move away from the com-
plexities of maintaining their networks. And while the reduced cost of an
Internet-based system might not be as great for the orthodontist as it is
for IBM, consider your IT spending over the last three years. Typical
orthodontists spend between one to two percent of their revenue on com-
puters and IT (and much more at startup), but many orthodontists are
shocked to see the actual amount on their yearly profit and loss statement.
In many cases, cost is secondary to the elimination of the regular
maintenance, backups, software updates and upgrades. Outsourcing your
IT can be a relief to your wallet and also to your psyche. But remember
that cloud computing will not eliminate your IT costs completely or your
need for IT support. Unless you are skilled and enjoy purchasing, install-
ing and maintaining your computers, you likely still will need a network
administrator.
Is accessing your office data like trying to reach patients in re-
tention? With cloud computing’s more centralized and open platform,
you can access your system anywhere at anytime. Because all of your
data is available 24/7 in a data facility, remote offices, home locations,
remote locations and mobile devices are all accessible to the same data-
base. This benefit is significant especially for larger offices that currently
are forced to use a variety of servers and software systems to connect.
Cloud computing eliminates this issue by only requiring an Internet con-
nection. In that data are stored on servers in the cloud, it is easy to ex-
pand and upgrade as you go. Using our previous example, let us say that
you run of out of drive space on your existing server. Instead of upgrad-
ing or replacing it, in the cloud you just pay for more space. This in-
creased flexibility is true for many aspects of computing including addi-
tional capacity, speed, processing power and user access. Costly software
licensing fees are eliminated as the systems are centralized in the cloud.
An example of a two office, 20-station setup is detailed in Table 1.
LIMITATIONS OF CLOUD COMPUTING
Do you get frustrated when you are at home checking your bank
activity and you lose your Internet connection? Imagine if your practice
management system went down on an August afternoon! The jump to
cloud computing means that you are dependent completely on your In-
ternet connection, which can be a scary fact for some users. While all
major service providers guarantee “uptime,” you should be sure to check
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Scholz
Table 1. Three-year hardware cost for a two office, 20-station setup.

Module Locally Hosted
Dell RAID SBS Server $15,500
20 Dell Optiplex Workstations $22,580
SATA Backup Unit & Media $1,250
VPN ROuterS $800
IT Support - Server + Workstations $14,400
Broadband Access - Cable or FIOS $12,600
Offsite Backup $7,200
Offsite Hosting $0
Total $74,330
your local providers upload, download and latency speeds and history
before signing up (you can test your broadband speeds easily at sites
Such as www.speedtest.net).
One way to reduce your Internet anxiety is to employ a secon-
dary connection such as a cellular router. These devices are inexpensive
and allow for a stable Internet connection that can run at relatively fast
speeds – currently up to 4G. In order to move to the cloud, you need to
feel confident that your Internet provider has fast and stable service.
Without this type of service, your daily mood might run in parallel with
the status bars of your Internet connection.
In the news section of your homepage, you are likely to read sto-
ries about Internet security issues on the Web at least once per week.
Survey data indicates that the biggest resistance to Internet-based com-
puting today involves fears around security. Clearly, healthcare data se-
curity is essential and most companies with cloud offering and services
include detailed service level agreements (SLA) that document in great
detail how your data is stored and made accessible to you.
In addition, some cloud-based systems employ “smart clients”
rather than browser-based clients. While not as ubiquitous as a browser,
a smart client provides much better security and, in many instances, im-
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Cloud Computing
proves the browsing experience significantly. Finally, systems that man-
age highly sensitive data often run on “private clouds” where information
is not shared with other customers and often is compliant with HIPAA
standards (Fig. 2).
A final limitation to cloud computing is the lack of integration
with third-party products. We often hear about the thousands of applica-
tions that are being developed each week for our mobile devices, but few
of these have any relevance to an orthodontist. Most orthodontic offices
rely on software programs to run their offices and currently, many of
these systems only offer a local solution. This situation is changing rap-
idly, however, as new software is being developed to integrate cloud sys-
tems together; the latest systems are being written directly on cloud-
based platforms. While this approach is likely to be the case for some
time, the development of large scale business apps such as Google apps,
increases the likelihood that orthodontic systems will replace desktop-
based software with cloud substitutes.
SHOULD I MOVE TO THE CLOUD”
The answer to this question depends on many factors that should
be evaluated by each orthodontist in his/her particular situation. Ques-
tions such as: “Can I get fast, reliable Internet service?” “What are my
current IT costs?” and “How much time does it take maintaining and
servicing my current server and IT?” should be addressed.
In some ways, the move to the cloud computing is based on the
belief that this is the direction computing is going. You certainly would
not want to spend $50K to outfit a brand new office with technology that
could become outdated quickly. On the other hand, although it is grow-
ing rapidly, cloud computing still runs a minority of small businesses and
will require more time to become fully mainstream. The U.S. is improv-
ing but still lags far behind in broadband speeds (Japan averages almost
20 mbps (mega-bits per second) up and down compared to less than 2
mbps in the U.S.), which undoubtedly will push more and more consum-
ers to the cloud. But ultimately, the decision to move to the cloud must
be based on the orthodontic practice management software behind it –
some of which have reduced functionality greatly. Just because software
runs in the cloud does not necessarily make it good.
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Scholz
Public Cloud Private Cloud
- Hosted at a Service Provider Site * Hosted at an Enterprise of a Service
• Supports multiple customers Provider site
- Supports one customer
- Does not utilize shared infrastructure
• Connectivity over private network/
fiber of the internet -
-Suited for information that is needs
a high level of security
- Often utilizes shared infrastructure
*Supports connectivity over the
internet
• Suited for information that is not
sensitive
*Can be cheaper than private cloud
Figure 2. A comparison of public and private cloud computing.
Last December, I attend the ninth annual Dreamforce cloud com-
puting conference in San Francisco. It was difficult to get a hotel room as
more than 40,000 attendees participated in the conference, which in-
cluded a keynote by former President Bill Clinton and a concert by
Stevie Wonder.
The most memorable moment of the conference for me occurred
On the rainy streets of San Francisco on the first day. In protest of the
new cloud-computing platform, Microsoft had sent dozens of employees
On Scooters to pass out anti-cloud propaganda (including umbrellas) to
the attendees. At one point, several of the pro-cloud supporters began
pushing, yelling and fighting with the Microsoft employees! The police
S00n arrived but not before a literal battle over the cloud had transpired.
It seems that the hype surrounding cloud computing has reached
a pitch in much of the business world as the old guard of software plat-
forms are being replaced by new ones in the cloud. And like any other
quickly ascending technology (i.e., iPads, TADs, 3D imaging), the truth
probably lies somewhere in the middle. While cloud computing will not
Solve all of your problems, there is a great deal of evidence to suggest it
s Worth a good hard look. It might not be time for every orthodontist to
Jump to the cloud, but it is apparent that cloud computing is here to stay.
















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Cloud Computing
FINAL REMARKS
Most data point to the stable growth of cloud computing tech-
nology, and more and more applications and systems are being built for
the cloud. Across the world we see a dramatic rise in mobile devices,
social media and on-demand technology. Certainly the world is becom-
ing more connected through these devices and systems.
Cloud computing offers a similar promise with its centralization
and open platform. In a perfect world, cloud computing would be as reli-
able as the electricity in your house. Until then, consider where you fall
on the early-/late-adopter curve. While it might be some time until cloud
computing reaches such a level of reliability, remember that only 15
years ago, it was hard to imagine you would manage most of your per-
sonal finances through an Internet browser. Today it is hard to imagine
actually going to a bank.
122
NEW TECH FOR DUMMIES
Robert P. Scholz
ABSTRACT
The other chapters in this volume have described a number of the new tech-
nologies that may be considered by orthodontists and many of us have or will
do just that. However, even though I have kept abreast of these newest devel-
opments, I have found myself not actually having used as many as some have
of my colleagues. This chapter is a summary of how I have dealt with the is-
sues related to new technologies and how these issues may be considered when
evaluating them. Technolocity, I'mfirstrage, Technobsolescence, Things That
Scare Me and The Now-Future are new self-coined words that will be used,
described and exampled.
KEY WORDS: technolocity, I’mfirstrage, technobsolescence, things that scare
me, the now-future
When I was asked by the planning committee to close and
summarize the 2011 Moyers Symposium, I was assigned the title: Tech-
nology in Private Practice: Where Do We Go From Here? After hear-
ing the excellent speakers who preceded me, I have taken the liberty of
changing the title to New Tech for Dummies. Each of our previous
speakers has described a new technology that will impact the private
practice of orthodontics now or in the near future, so my review of their
presentations would be redundant. Instead, I shall attempt to provide a
more global, bird’s eye view of how I have ridden the technology ex-
plosion wave, how I perceive it and how I deal with it today.
First, let me share with you some self-coined words I have
come to use frequently; they will be defined as we come across them in
the presentation:
1. Technolocity
2. I’mfirstrage
3. Technobsolescence
123
New Tech for Dummies
4. Things That Scare Me
5. The NOW-Future
It is important to understand my professional history and pre-
sent activities so that when my current behaviors are discussed with new
technology, the decision can be made whether or not my approach is
something you might choose to emulate.
I enjoyed the private practice of orthodontics for forty years in
the San Francisco Bay Area; that practice was shared most of those
years with a partner. For twenty years during that time, I held a half-
time appointment as Clinical Professor at the University of California
San Francisco. After leaving private practice in 2003, I have been focus-
ing on my current assignments as the liaison person to orthodontic
graduate programs for Ortho Computer Systems (Ortho2, Ames, LA),
and I also serve as Associate Editor of Techno Bytes, the technology
section of the American Journal of Orthodontics and Dentofacial Or-
thopedics. I also hold Adjunct Professor positions at the University of
North Carolina Chapel Hill and Temple University in Philadelphia.
When I see a new technological development, I ask myself
these questions:
• What am I currently using to achieve the desired re-
sult and how is it working?
• How does the new technology work?
• What is the learning curve?
• What is the cost and is it cost effective?
• What about technobsolescence, which means is this
device going to have added features and cost half as
much a year from now?
Then I apply the adage.... If it ain't broke ... Don't fix it. This
attitude may put me behind the game with new technology, but what I
currently use works just fine!
Yes, I have a cell phone, but it is not a Smartphone; it is a dumb
phone and has all the features I need, so it will be with me for a while. If
Dr. McNamara reminds me I need to call him about something, he will
see me make a note on what I call my Portuguese Palm Pilot (Fig. 1).
This small paper notebook and small ballpoint pen accompany
me most of the time. The notebook has unlimited storage, a handy delete
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Scholz
Figure 1. The Portuguese Palm Pilot.
feature by striking out the entry with a pen, no batteries are required and
if I should drop it, it still works!
Technolocity is the incredible velocity at which technology is
Smacking the world up alongside the head. Do we have to buy it to see
how it really works? Here is an example I encountered about ten years ago:
My old watch was accurate and slipped onto my wrist easily
With a spring-loaded wristband, but it had to be adjusted manually for
time zone changes. Occasionally, when my time-keeping devices like
the Computer, fax machine, kitchen clock and alarm clock got out of
Sync, I would call Ma Bell and set all these devices to the current time.
The new watch was advertised to keep accurate by connecting to the
atomic clock. It had a button for changing time zones as well as an “ad-
Justable” wristband. So I purchased the new watch and spent consider-
able time trying to get the “adjustable” wristband adjusted to my large
hand connected to a slim wrist. I ended up using an explorer to remove


New Tech for Dummies
the tiny pins that allowed removal of some links, so I do not understand
to this day how a non-dentist could adjust this wristband.
The other non-advertised feature of the new watch was that the
time zone chip had not yet been invented, so flying to New York meant
pushing the button exactly twenty-one times to get the watch to read
Eastern time. Eventually the battery died, so I discarded the new watch
and reverted back to the old watch that I wear today.
Another new tech phenomenon, the I'mfirstrage, is the strong
desire some people have to be the first in the world to have the new de-
vice. I still can envision the news flash when the first iPhone was pur-
chased with much hoorah and was soon outshined by the excitement of
the purchase of the first iPad. Both of these devices have suffered from
technobsolescence – how fast is that new, expensive widget I just
bought going to become obsolete? We all know how both the iPhone
and iPad experienced some serious technobsolescence.
Another example of technobsolescence I experienced about ten
years ago was the purchase of the eBook that had an online catalog with
suggestions. Books could be downloaded and charged to your credit
card via a dial-up modem. The eBook could store 25 books, had a touch
word dictionary and cost about $300. The reality was that it was slightly
bulky, difficult to see and was a bit expensive. The two features of be-
ing able to hold 25 books and immediate book availability were of no
use to me, so I gave it a grade of “technology for technology’s sake”
and returned it. The eBook suffered serious technobsolescence and we
all know reading from a device’s screen can now be undertaken in many ways.
The first Kindle went on the market on November 19, 2007 for
$399, sold out in five and a half hours and was out of stock for five
months. It could store 200 non-illustrated books, which begs the ques-
tion: who needs 200 books in their pocket? The first generation Kindle
was replaced 15 months later by the Kindle2 on February 10, 2009, sold
for $359, could read aloud and store 1500 non-illustrated books. Price
changes occurred that same year on July 8, 2009 ($299) and October 7,
2009 ($259). So here is a synopsis of the evolution of the Kindle:
• Kindle (original, white) November 19, 2007
• Kindle2 (white) February 23, 2009
• Kindle2 International (white) October 19, 2009
• Kindle 3-3G and Wi-Fi (white/graphite) August 27,
2010
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Scholz
• Kindle DX (original, white) June 10, 2009
• Kindle DX International (original, white) January
19, 2010
• Kindle DX International 2 (graphite) July 17, 2010
• Kindle 3 Wi-Fi (graphite) August 27, 2010
My Kindle became a dinosaur in late 2009 when the Kindle ap-
plication could be downloaded freely for Windows 7, Vista and XP; a
Kindle unit, therefore, no longer was required and e-books could be
purchased from amazon.com. In that my Dell XPS laptop travels with
me at all times, the Kindle has been retired.
Other examples of technobsolescence include the disappearance
of Blockbuster stores, who were slow in comprehending that they would
become dinosaurs with the advent of the Netflix concept. Netflix now
may be in danger with the many on-demand devices coming on the
market. My neighbor city of San Francisco is the first city to stop mak-
ing the Yellow Pages book; one must request a copy before it will be
provided.
And now on to Things That Scare Me. All this new technology
enables us to become more mobile, but do we need more mobility or is
it technology for technology’s sake? My mobility with the Dell XPS is
enough as I do not need my email device in my pocket because my
dumb phone will voice me new emails. Plus, all this new technology
opens us to much more scamming. Allow me to share three examples of
Things That Scare Me.
I recently received an email message, seemingly from my son
Craig. “I’m stuck in London as my wallet and passport were stolen.
Please send some money so I can buy a ticket home.” His new Droid
cell phone allowed a hacker to send this message to all of his email ad-
dresses, and then deleted his address book and all past email messages
both sent and received.
In the city of Palo Alto, CA, 911 calls average approximately
100 per day. In January 2011, the 911 Center received over 1,000 calls.
It turned out that the villain was a vehicle that could call 911 in an acci-
dent; it malfunctioned and called 911 every 20 seconds all day.
The Stanford Who program allows Stanford University students
to locate each other. But it is a public program, so if I can get the name
of a Stanford coed, I can get her home address. If you take your own
picture with your Smartphone, a stalker can know exactly where you are!
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New Tech for Dummies
Let’s finish with some thoughts on The Now-Future. The Sony
prototype flexible color video screen is small enough to be rolled
around a pencil. The Flexible Display Center at Arizona State Univer-
sity hopes to have flexible displays ready for test trials in approximately
three years. The possibilities of using flexible displays are endless and
one day will be used in many portable devices such as e-readers, cell
phones and tablets.
You now can pay for items with your cell phone. Customers
who own an iPhone, iPod Touch or Blackberry can pay with their phone
by simply downloading the app, Selecting an icon (e.g., Starbucks) and
holding the on-screen bar code up to a scanner at the counter. Starbucks
claims that more than one-third of its U.S. customers use Smartphones;
nearly three quarters of these use BlackBerry or iPhone mobile devices.
“Faces in 4D: Why the 4th Dimension?” is the title of a paper
that Dr. Carroll-Ann Trotman from the University of Maryland submit-
ted to the AJO-DO. Clinicians will be able to record and quantify auto-
matically the face during motion, so will the current move to diagnosing
in three dimensions soon be replaced by 4D records?
The cloud (see the chapter on cloud computing by Craig Scholz
in this volume) allows your management program and your data to be
stored at a remote, secure data storage bank instead of locally in your
office. This approach clearly is where the world is going. It means:
• No more backups
* No more down time to update
• No need for interoffice connectivity
• More cost effective
A comparison of the hardware costs for two offices with 20
workstations is shown in Table 1.
The television show Jeopardy recently pitted previously big
winners Brad and Ken against an IBM trained megacomputer called
Watson. Watson won hands down. Is the day coming when computers
with artificial intelligence will diagnose and plan treatment for us? And
intraoral scanners are on the way, so will the orthodontic staff not be
taking impressions soon?
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Scholz

3- YEAR HARDWARE COST FOR 2 OFFICES WITH 20 STATIONS
Local Cloud
Dell RAID SBS Server $15,500 $0
20 Dell Optiplex Workstations $22,580 $22,580
SATA Backup Unit & Media $1,250 $0
VPN ROuterS $800 $800
IT Support: Server & Workstations $14,400 $4,500
Broadband Access: Cable or FIOS $12,600 $12,600
Offsite Backup $7,200 $0
Offsite Hosting $0 $10,800
TOTALS $74,330 $51,280
Today’s most dramatic new technology likely is the arrival of
the CBCT systems. In 2001, there were three CBCTs installed in the
U.S.; in 2011, there are more than 4,000. As more and more practices
begin obtaining CBCT scans on all their case starts, the old records ap-
pointment may disappear and be replaced. If we look into the future a
bit, we soon may see:

OLD VS. NEW DIAGNOSTIC RECORDS
TODAY TOMORROW
Impressions Bite registration
Panoramic radiograph Photos
Cephalogram CBCT exposure
Bite registration Fifteen minutes
Photos
One hour
Radiation is the CBCT buzz word these days, but I think the
public concerns soon will disappear with some good education and sys-
tem improvements. Below are some comparisons (Figs. 2-4).
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New Tech for Dummies
Medical Effective Doses (usw)
900
800
700
600
500
400
300
200
100
O
i-CAT LFOV Chest X-ray Medical CT
Figure 2. CBCT versus medical dosimetry. Modified from a
figure provided by Dr. Aaron Molen.
400 Dental Effective Doses (usw-ICRP 2007)
350
300
250
200
150
100
50
Daily Weekly Digital Digital Analog i-CAT
Ambient Ambient FMX FMX FMX Nexøen
Radiation Radiation (low) (high) (D Spd-Rnd) LFOV
Figure 3. Patient risk related to common dental radiographic
examinations. Data from Ludlow et al., 2008.


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Scholz
Stochastic Effect: A Little Perspective
1:740,000 developing cancer (16x10cm, 5 sec
1:700,000 dying from dogbite
1:270,000 developing cancer (17x23cm, 9 sec)
1:108,000 dying in an explosion
1:19,000 dying in a car accident
1:18,000 being murdered
0 200,000 400,000 600,000 800,000
Figure 4. Relative risks in life. Modified from a figure pro-
vided by Dr. Aaron Molen.
Just for fun, I asked three of my expert friends to list the most
important new tech issues that will affect the practice of orthodontics.
These are their responses:
They all agreed:
* Everything will be in the cloud;
* 2D radiographs are on their way out:
* We will be cone beaming all our starts; and
* Impressions will disappear.
Each offered some individual responses:
* More orthodontics by the general practitioner;
* Invisalign:
* Insignia;
* Incognito:
• GP referrals will decrease and be replaced by good
websites:






| 3 |
New Tech for Dummies
• Word-of-mouth patient referrals will be replaced by
social networking; and
• Online scheduling by some patients.
The day I have been anticipating has arrived when the cell
phone, iPod, Kindle, laptop, GPS, wristwatch and movie player have
become one single device – check out the Motorola Atrix 4G, a dual-
core Smartphone with online computer power.
FINAL REMARKS
So now you know about some of the issues surrounding new
technology; I hope that you will consider them when tech deliberat-
Ing. ...
• Technolocity
• I’mfirstrage
• Technobsolescence
• Things That Scare Me
• The Now-Future
And please remember – there is a great deal of new technology here
today and even more coming tomorrow. Much of it will be useful to
make us more effective in what we do but there is much out there that is
technology just for technologies sake. Beware the new technology that
is out there simply looking for a problem to solve.
REFERENCE
Ludlow JB, Davies-Ludlow LE, White SC. Patient risk related to com-
mon radiographic examinations: The impact of 2007 International
Commission on Radiological Protection recommendations regarding
dose calculation. J Am Dent Assoc 2008; 139;1237-1243.
132
THE USE OF 3D IMAGING TO ADVANCE
YOUR PRACTICE
Lucia H.S. Cevidanes, Cauby Maya Chaves Jr.,
Abeer Alhadidi, Martin Styner, Beatriz Paniagua
ABSTRACT
The knowledge gained from three-dimensional (3D) imaging over the last dec-
ade has allowed more effective and rational clinical decision-making for specific
orthodontic patients. However, investigations on whether the use of 3D imaging
changes the orthodontic diagnosis and treatment planning are needed. The indi-
cations of cone-beam computed tomography (CBCT) imaging include patients
with impacted teeth, delayed or ectopic eruption path, root resorption, temporo-
mandibular joint (TMJ) degenerative conditions, facial asymmetry, orthognathic
Surgical planning and simulation, craniofacial anomalies, trauma and patholo-
gieS.
The purposes of this chapter are to illustrate clinical applications of 3D
CBCT in the orthodontic practice and discuss challenges in quantitative analysis
of morphological changes over time in light of the underlying biological pro-
cesses that lead to those changes. Using an existing longitudinal dataset of
CBCTs for orthodontic/surgical corrections for different skeletal malocclusions,
this chapter discusses how changes over time in 3D-registered images are meas-
ured to assess outcomes of treatment.
KEY WORDS: CBCT, diagnosis, treatment planning, superimpositions, treatment
OutCOmeS
INTRODUCTION
Before any three-dimensional (3D) diagnostic assessment of fa-
cial morphology at baseline or over time can advance the orthodontic
practice, such assessment needs to be based in the biology of craniofacial
growth. To date, our understanding of facial growth still is guided by
pioneer studies (e.g., Melsen, 1967, 1972; Solow, 1969; Enlow and
Moyers, 1971; McNamara, 1972; Petrovic, 1974; Björk and Skieller,
1977, 1983).
133
Use of 3D Imaging
Cone-beam computed tomography (CBCT) imaging offers or-
thodontists an opportunity to learn more about the craniofacial structures
we treat and to be more scientific. The use of CBCT technology has to
allow for additional diagnostic data and the possibility to provide better
service to the patients. It still needs to be determined whether the use of
CBCT indeed allows a more comprehensive diagnosis and whether such
a diagnosis would change the treatment plan or improve the treatment
outcomes (Palomo, 2011).
Johnston (2011) stated that for now, CBCT is mostly an expen-
sive technology in search of questions, important or otherwise. There is a
consensus, however, that no previous imaging or basic science methods
have been able to explain the variability of patient facial growth and re-
sponse to treatment. Orthodontics remains partly art, and many important
scientific questions have not been answered. Whether our use of CBCT
can help answer those valid clinical questions remains to be seen.
As 3D image analyses are implemented by the orthodontist, our
mistakes and failures in two-dimensional (2D) cephalometrics should not
be repeated in 3D. It is important to learn from the historical efforts in
orthodontics, dentistry and medicine. Several studies (Baumrind et al.,
1976; Moyers and Bookstein, 1979; Johnston, 2011) agree that there is
no theory of cephalometrics, only conventions that involve landmarks
and lines. Even if lines are not straight but curves, they still are just lines
(i.e., a simplification of the 3D craniofacial structures). These simplifica-
tions fail to capture changes of shape and size for 3D structures and mis-
represent growth, portraying it as vector displacement rather than a gen-
eralized distortion.
3D registration procedures have been described previously (Ce-
vidanes et al., 2005a, 2006); this chapter will discuss approaches to
measure changes over time. 3D CBCT images now are obtained easily in
many dental centers and should overcome the shortcomings of 2D
radiography, but the ability to visualize the craniofacial complex in 3D
does not imply the ability to quantify growth or treatment changes in 3D.
The analysis tools for 3D images, specifically color maps and 3D Closest
Point quantification, have been adapted by us for use with CBCTs of the
craniofacial complex. However, the Closest Point method measures dis-
placement that occurs with orthognathic surgery as the smallest separa-
tion between the boundaries of the same structure, which may or may not
be the appropriate directional distance between equivalent boundaries or
landmarks on pre- and post-surgery images. The Closest Point method,
however, cannot be used to quantify longitudinal changes and fails to
134
Cevidanes et al.
quantify rotational and large translational movements. Other 3D mor-
phometric approaches under development also will be discussed in this chapter.
WHY AND WHEN TO USE 3D CBCT IMAGING FOR
DIAGNOSIS AND TREATMENT PLANNING
Even though some clinicians have used CBCT routinely in
orthodontic practice, there are questions on whether the diagnostic bene-
fits justify the radiation dose and the routine use of CBCT. Current ap-
plications of 3D CBCT imaging in orthodontics include the following
diagnosis and assessment of treatment for complex orthodontic condi-
tions.
Alveolar Bone and Tooth Morphology and Relative Position
CBCT allows evaluation of buccal and lingual plates of the al-
Veolar bone, bone loss or formation, bone depth and height, presence or
absence of unerupted teeth, tooth development, tooth morphology and
position, amount of bone covering the tooth and proximity or resorption
of adjacent teeth. For such application, the image acquisition can utilize a
Small or medium field of view that includes an arch quadrant or both up-
per and lower arches, depending on the clinical indication (Fig. 1). Such
findings in CBCT images may lead to modifications in treatment plan-
ning (e.g., avoid extraction, change plan of which tooth to extract, or
placement of bone plates and mini-screws), reduced treatment duration
and improved control of additional root resorption (Tamimi and El Said,
2009; Treil et al., 2009; Becker et al., 2010; Katheria et al., 2010; Leung
et al., 2010; Leuzinger et al., 2010; Molen, 2010; Sherrard et al., 2010;
Tai et al., 2010; Van Elslande et al., 2010; Botticelli et al., 2011;
Shemesh et al., 2011).
Temporomandibular Joint (TMJ) Evaluation
CBCT images provide clinicians with the opportunity to visual-
ize and quantify the local and regional effects associated with TMJ ab-
normalities (Fig. 2). For this reason, CBCT recently has replaced other
imaging modalities as the modality of choice to study TMJ bony changes
(Helenius et al., 2005; Koyama et al., 2007; Alexiou et al., 2009). For
detecting TMJ bony changes, panoramic radiography and MRI have only
poor to marginal sensitivity (Ahmad et al., 2009).
The Research Diagnostic Criteria for Temporomandibular Dis-
orders (RDC/TMD; Dworkin and LeResche, 1992) was revised recently
to include image analysis criteria for various imaging modalities (Ahmad
135
Use of 3D Imaging
Figure 1. Impacted upper right canine erupting toward the up-
per right central incisor. Close-up views reveal marked root
resorption of the right central incisor. Orthodontic mechanics
need to be planned carefully to avoid additional root damage.
et al., 2009). The RDC/TMD validation project (Schiffman et al.,
2010a,b; Truelove et al., 2010) concluded that revised clinical criteria
alone, without recourse to imaging, are inadequate for valid diagnosis of
TMD and previously had underestimated the prevalence of bony changes
in the TMJ. TMJ pathologies that result in alterations in the size, form.
quality and spatial relationships of the osseous joint components lead to
skeletal and dental discrepancies in all three planes of space. In affected
condyles, the perturbed growth and/or bone remodeling, resorption and
apposition can lead to progressive bite changes that are accompanied by
compensations in the maxilla, “non-affected” side of the mandible, tooth
position, occlusion and articular fossa, and unpredictable orthodontic
outcomes (Bryndahl et al., 2006; Kapila et al., 2011).
Airway Assessment
Several recent studies have assessed airway morphology and
changes over time with surgery, growth and its relationship to obstructive
sleep apnea (Aboudara et al., 2003: Sera et al., 2003; Ogawa et al., 2005:

136
Cevidanes et al.
© Q & Q
V8 one-year post-surgery V9two years post-surgery
A V2 pre-surgery V2 splint removal at the end of orthodontics one year ºorthodontic retention
sºººººº.
ses Q sºs O
F V6-V2 V8-V6 wo-V8
Figure 2. Longitudinal follow-up of bone remodeling in the left condyle. A:
Condylar morphology prior to surgery, at splint removal, one year post-surgery
and two years post-surgery, B-E: Absolute distances and difference vectors. B:
Pre-surgery subtracted from splint removal. C. Splint removal subtracted from
One year post-surgery. D. One year post-surgery subtracted from two years post
Surgery. E. Pre-surgery subtracted from two years post-surgery. F. Visualization
of changes using signed distances, where bone formation is shown in red, 4 mm
of bone resorption in the superior and articular surfaces in blue.
Osorio et al., 2008; Strauss and Burgoyne, 2008; Tso et al., 2009; El and
Palomo, 2010; Lenza et al., 2010; Schendel and Hatcher, 2010; Abram-
son et al., 2011; Conley, 2011; El et al., 2011; Iwasaki et al., 2011; Oh et
al., 2011; Schendel et al., 2011). CBCT has been used to measure the
airway shape, minimum cross-sectional area and volume; however, air-
Way measurements have a number of challenges. The boundaries of the
nasopharynx and oropharynx respectively with the maxillary/paranasal
sinuses and the oral cavity/inferior boundary are not consistent among
subjects and image acquisitions; airway shape and volume will vary
markedly with functional stage of the dynamic process of breathing and
head posture. Longitudinal studies of mandibular setback surgery have
not shown consistent reduction of airway space, nor have mandibular
propulsion devices shown enlargement of the airway space that might be
helpful for obstructive breathing conditions (Fig. 3).



137
Use of 3D Imaging
Dre-Surgery splint removal one year post-surgery
before Herbst. after Herbst
Figure 3. Airway changes overtime do not necessarily follow skeletal
changes in these examples. The top row shows follow-up of maxillary
advancement and mandibular setup back surgery. Note that despite the
mandibular setback, the airway configuration remained similar at splint
removal and one year post-surgery. The bottom row shows cross-
sectional images from a patient treatment with Herbst appliance, where
the airway actually appeared narrower after treatment.
Dentofacial Deformities and Craniofacial Anomalies
CBCT imaging offers the ability to analyze facial asymmetry
and anteroposterior, vertical and transverse discrepancies (Fig. 4). The
virtual treatment simulations can be used for treatment planning in Or-
thopedic corrections and orthognathic surgery. Computer-aided jaw
surgery is increasingly in use clinically due to the possibility to
incorporate a high level of precision for accurately transferring virtual
plans into the operating room. In complex cases, follow-up CBCT acqui-
sitions for growth observation, treatment progress and post-treatment
observations, may be helpful to assess stability of the correction Over
time (Schendel and Lane, 2009; Carvalho et al., 2010; Cevidanes et al.,
2010; Ebner et al., 2010; Edwards, 2010; Heyman et al., 2010; Jayaratne
et al., 2010a,b; Orentlicher et al., 2010; Popat and Richmond, 2010.
Scolozzi and Terzic, 2010; Tucker et al., 2010; Abou-Elfetouh et al.,
2011; Agarwal, 2011; Almeida et al., 2011; Behnia et al., 2011; Dales:
sandri et al., 2011; Gateno et al., 2011; Kim et al., 2011; Lloyd et al., 201 1).

138
Cevidanes et al.
Figure 4. CBCT use for diagnosis of facial asymmetry. The patient had been
diagnosed with mandibular hypertrophy; however, the CBCT revealed compo-
lents of maxillary and mandibular asymmetry. Stereolithographic models were
built for treatment planning for this patient. The surgeon’s assessment of the
Stereolithographic models indicated the need to remove bone in the maxilla and
mandibular corpus (marked lines), as the right mandibular corpus appeared to be
longer Vertically than the opposite side. However, virtual correction of mandibu-
lar yaw and roll (purple models) compared to the patient’s actual model (gray),
shows that if the positional 3D cant of the mandible is corrected, the mirror im-
*ges reveal that vertical length of the corpus is similar in the left and right sides
mirrors. The analysis of the virtual surface models reveal that the mandible is
less asymmetric than indicated by the clinical exam or visualized in the stereo-
lithographic models.

139
Use of 3D Imaging
THE USE OF CBCT FOR ASSESSMENT
OF TREATMENT OUTCOMES
Over the last decade, longitudinal CBCT images have been used
for assessment of treatment outcomes. Even with the availability of 3D
images, there are critical barriers that have to be overcome before longi-
tudinal quantitative assessment of the craniofacial complex can be per-
formed routinely:
1. Radiation dose: The use of 3D images for treatment
planning and follow-up raises concerns regarding ra-
diation dose.
2. Construction of 3D surface models: Longitudinal
quantitative assessment of growth and surgical cor-
rection requires construction of 3D surface models.
Segmentation – the process of constructing 3D mod-
els by examining cross-sections of a volumetric data
set to outline the shape of structures – remains a chal-
lenge (Adams and Bischof, 1994; Lie, 1995; Ma and
Manjunath, 2000; Moon et al., 2002). Many standard
automatic segmentation methods fail when applied to
the complex anatomy of patients with facial deform-
ity. The methods described by Gerig and coworkers
(2003) and Yushkevich and colleagues (2006) address
these technical difficulties and have been adapted by
Cevidanes and associates (Cevidanes et al., 2005a,
2006) in our laboratory to construct 3D craniofacial
models.
3. Image registration is a core technology for many im-
aging tasks. The two obstacles to widespread clinical
use of non-rigid (elastic and deformable) registration
are computational cost and quantification difficulties
that arise as the 3D models are deformed (Christensen
et al., 1996; Rueckert et al., 1999; Hajnal et al., 2001;
Crum et al., 2004). Non-rigid registration is required
to create a composite of several different jaw shapes
pre-operatively to guide the construction of 3D sur-
face models (Thompson et al., 1997). However, to
evaluate surgical displacements, rigid registration has
advantages for longitudinal assessments (Maes et al.,
1997). A novel sequence of fully automated voxel-
140
Cevidanes et al.
wise rigid registration at the cranial base and super-
imposition (overlay) methods has been developed
(Cevidanes et al., 2005a,b, 2006). The major strength
of this method is that registration does not depend on
the precision of the 3D surface models. The cranial
base models are used only to mask anatomic struc-
tures that change with growth and treatment. The reg-
istration procedures actually compare voxel by Voxel
of gray-level CBCT images, containing only the cra-
nial base, to calculate rotation and translation parame-
ters between the two images. Regional superimposi-
tion in the anterior cranial base does not define the
movement of the mandible relative to the maxilla
completely. Future studies are needed to investigate
the use of different 3D regional superimposition ar-
eas. Currently, superimposition of 3D surface models
is still too time consuming and computing intensive to
apply these methods in routine clinical use. Our cur-
rent focus is on developing a simplified analysis so
that soon these methods can be used clinically.
. Quantitative measurements: Precise quantitative
measurement is required to assess the placement of
bones in the desired position, the remodeling of bone,
the position of Surgical cuts and fixation screws
and/or plates relative to risk structures. Current quan-
tification methods include:
a. Volume changes (Thompson et al., 1997) re-
flect increase or decrease in size, but struc-
tural changes at specific locations are not re-
flected sufficiently in volume measure-
mentS.
b. Landmark-based measurements (Rohr,
2001) present errors related to landmark
identification. Locating 3D landmarks on
complex curving structures is not a trivial
problem for representation of components of
craniofacial form (Dean et al., 2000). Book-
stein (1991) noted that a lack of literature
exists regarding suitable operational defini-
tions for the landmarks in the three planes of
141
Use of 3D Imaging
space (coronal, Sagittal and axial). Gunz and
coworkers (2004) and Andresen and associ-
ates (2000) proposed the use of semi-
landmarks (i.e., landmarks plus vectors and
tangent planes that define their location), but
information from the whole curves and sur-
faces also must be included. The studies of
Subsol and colleagues (1998) and Andresen
and coworkers (2000) provided clear ad-
vances toward studies of curves or surfaces
in 3D, referring to tens of thousands of 3D
points to define geometry.
c. Closest Point measurements between the
surfaces can display changes with color
maps as proposed by Gerig and associates
(2001). However, the Closest Point method
measures closest distances, not correspond-
ing distances between anatomical points on
two or more longitudinally obtained images
(Fig. 5). For this reason, the Closest Point
measurements completely fail to quantify
rotational and large translational move-
ments. This method cannot be used for lon-
gitudinal assessments of growth or treatment
changes, nor for the analysis of physiologic
adaptations, such as bone remodeling that
follows surgery.
d. Shape correspondence: The SPHARM-
PDM framework (Gerig et al., 2001; Styner
et al., 2006) was developed as part of the
National Alliance of Medical Image
Computing, (NA-MIC, NIH Roadmap for
Medical Research) and has been adapted for
use with CBCTs of the craniofacial complex
(Paniagua et al., 2011a,b). SPHARM-PDM
is a tool that computes point-based models
using a parametric boundary description for the
142
Cevidanes et al.
Measurement of condylar displacement distances and vectors
D post-surgery
| pre-surgery
Closest point Shape correspondence
Figure 5. Simplified diagram for comparison between closest point
surface distances and corresponding distances. Note that the closest
surface points fail to quantify the displacement changes.
computing of shape analysis. The 3D virtual sur-
face models are converted into a corresponding
spherical harmonic description (SPHARM),
which then is sampled into a triangulated surface
(SPHARM-PDM). This work presents an
improvement in outcome measurement as
compared to Closest Point correspondence (CP)-
based analysis. This standard analysis currently
is used by most commercial and academic
softwares, but it does not map corresponding
surfaces based in anatomical geometry and
usually underestimates rotational and large
translational movements. CP color maps
measure surgical jaw displacement as the
smallest separation between boundaries of the
same structure that may not be the right
anatomical corresponding boundaries on pre-
and post-surgery anatomical structures (Fig. 6).
FINAL CONSIDERATIONS
This paper discusses applications of CBCT in clinical practice
and how change is measured over time in 3D-registered images to assess
Outcomes of treatment. Applications of CBCT should be justified on an
individual basis by demonstrating that the benefits to the patient’s clini-
cal condition. Assessments of longitudinal 3D changes require precise
quantitative methods. While the Shape Analysis procedures described in
this chapter are an improvement over Closest Point surface distances,
future investigations on 3D craniofacial morphometric methods are needed.

143
Use of 3D Imaging
Pre-surgery to one year post-surgery
O pre-surgery
one year post-surgery
- Corresponding Closest point
corresponding distances distances
vectors shown in
pre-surgical shown in pre-surgical shown in one year post-surgical model
odel - Q
0mm-13mm -10mm- 10mm -13mm-13mm -5mm-7mm
Figure 6. Differences in quantification with Closest Point surface distance com-
pared to shape correspondence illustrated in a follow-up of a two-jaw surgical
procedure where marked ramus bone resorption occurred post-surgery. The par
tient was treated with maxillary advancement and mandibular setback with
downward displacement of the mandibular corpus. The top row shows semi-
transparent overlays of pre-surgery and one year post-surgery mandibular model
with two different degrees of transparent overlay to allow better visualization of
changes overtime. The bottom row shows color maps for comparison of meas:
urements using shape correspondence versus Closest Point surface distances.
REFERENCES
Aboudara CA, Hatcher D. Nielsen IL, Miller A. A three-dimensional
evaluation of the upper airway in adolescents. Orthod Craniofacial
Res 2003;6 S1:173–175.
Abou-Elfetouh A, Barakat A, Abdel-Ghany K. Computed-guided rapid-
prototyped templates for segmental mandibular osteotomies: A pre-
liminary report. Int J Med Robot 2011;7: 187-192.
Abramson Z, Susaria SM, Lawler M. Bouchard C, Troulis M. Kaban LB.
Three-dimensional computed tomographic airway analysis of patients
with obstructive sleep apnea treated by maxillomandibular advance-
ment. J Oral Maxillofac Surg 2011;69:677-686.




144
Cevidanes et al.
Adams R, Bischof L. Seeded region growing. IEEE Trans Pattern Anal
1994; 16:641–647.
Agarwal R. Anthropometric evaluation of complete unilateral cleft lip
nose with cone beam CT in early childhood. J Plast Reconstr Aesthet
Surg 2011:64:e 181-e 182.
Ahmad M, Hollender L., Anderson Q, Kartha K, Ohrbach RK, Truelove
EL, John MT, Schiffman EL. Research diagnostic criteria for tem-
poromandibular disorders (RDC/TMD): Development of image analy-
sis criteria and examiner reliability for image analysis. Oral Surg Oral
Med Oral Pathol Oral Radiol Endod 2009; 107:844-860.
Alexiou K, Stamatakis H, Tsiklakis K. Evaluation of the severity of tem-
poromandibular joint osteoarthritic changes related to age using cone
beam computed tomography. Dentomaxillofac Radiol 2009:38; 141-
147.
Almeida RC, Cevidanes LH, Carvalho FA, Motta AT, Almeida MA,
Styner M, Turvey T, Proffit WR, Phillips C. Soft tissue response to
mandibular advancement using 3D CBCT scanning. Int. J Oral Maxil-
lofac Surg 2011:40:353–359.
Andresen R, Bookstein F L., Conradsen K, Ersboll BK, Marsh JL, Krei-
borg S. Surface-bounded growth modeling applied to human mandi-
bles. IEEE Trans Med Imaging 2000; 19:1053-1063.
Baumrind S, Miller D, Molthen R. The reliability of head film measure-
ments: 3. Tracing superimposition. Am J Orthod 1976;70:617-644.
Becker A, Chaushu C, Casap-Caspi N. Cone-beam computed tomogra-
phy and the orthosurgical management of impacted teeth. J Am Dent
Assoc 2010; 141; 14S-18S.
Behnia H, Khojasteh A, Soleimani M, Tehranchi A, Atashi A. Repair of
alveolar cleft defect with mesenchymal stem cells and platelet derived
growth factors: A preliminary report. J Craniomaxillofac Surg 2011;
March 17 [Epub ahead of print].
Björk A, Skieller V. Growth of the maxilla in three dimensions as re-
vealed radiographically by the implant method. Br J Orthod 1977;4:
53-64.
Björk A, Skieller V. Normal and abnormal growth of the mandible: A
Synthesis of longitudinal cephalometric implant studies over a period
of 25 years. Eur J Orthod 1983;5:1-46.
Alling CC, Helfrick JF, Alling RD. Impacted maxillary teeth. In: Im-
pacted Teeth. Philadelphia: WB Saunders 1993:247-269.
145
Use of 3D Imaging
Bookstein FL. Morphometric Tools for Landmark Data, 1st ed. Cam-
bridge: Cambridge University Press 1991:435.
Botticelli S, Verna C, Cattaneo PM, Heidmann J, Melsen B. Two- versus
three-dimensional imaging in subjects with unerupted maxillary ca-
nines. Eur J Orthod 2011:33:344–349.
Bryndahl F, Eriksson L, Legrell PE, Isberg A. Bilateral TMJ disk dis-
placement induces mandibular retrognathia. J Dent Res 2006:85:
1 118-1123.
Carvalho Fde A, Cevidanes LH, da Motta AT, Almeida MA, Phillips C.
Three-dimensional assessment of mandibular advancement one year
after surgery. Am J Orthod Dentofac Orthop 2010;137 S4:S53.el-el2.
Cevidanes LHS, Bailey LTJ, Tucker GR Jr, Styner MA, Mol A, Phillips
CL, Proffit WR, Turvey T. Superimposition of 3D cone-beam CT
models of orthognathic surgery patients. Dentomaxillofac Radiol
2005a:34: 1-9.
Cevidanes LHS, Phillips CL, Tulloch JFC, Proffit WR. Superimposition
of 3D cone-beam CT models of orthognathic surgery patients. In:
McNamara JA Jr, Kapila SD, ed. Digital Radiography and Three-
dimensional Imaging. Monograph 43, Craniofacial Growth Series,
Department of Orthodontics and Pediatric Dentistry and Center for
Human Growth and Development, The University of Michigan, Ann
Arbor 2005b;105-122.
Cevidanes LHS, Styner MA, Proffit WR. Image analysis and superimpo-
sition of 3D cone-beam CT models. Am J Orthod Dentofacial Orthop
2006;129:611-618.
Cevidanes LHS, Tucker S, Styner M, Kim H, Chapuis J, Reyes M, Prof-
fit W, Turvey T, Jaskolka M. Three-dimensional surgical simulation.
Am J Orthod Dentofacial Orthop 2010;138:361-371.
Christensen GE, Rabbitt RD, Miller MI. Deformable templates using
large deformation kinematics. IEEE Trans Image Process 1996;5:
1435–1447.
Conley RS. Evidence for dental and dental specialty treatment of ob-
structive sleep apnoea. Part 1: The adult OSA patient. Part 2: The pe-
diatric and adolescent patient. J Oral Rehabil 2011:38:136-156.
Crum WR, Hartkens T, Hill DL. Non-rigid image registration: Theory
and practice. Br J Radiol 2004;77 Spec No 2:S140-S153.
146
Cevidanes et al.
Dalessandri D, Laffranchi L, Tonni I, Zoti F, Piancino MG, Paganelli C,
Bracco P. Advantages of cone beam computed tomography (CBCT)
in the orthodontic treatment planning of cleidocranial dysplasia pa-
tients: A case report. Head Face Med 2011;7:6.
Dean D, Hans MG, Bookstein FL, Subramanyan K. Three-dimensional
Bolton-Brush growth study landmark data: Ontogeny and sexual di-
morphism of the Bolton Standards cohort. Cleft Palate Craniofac J
2000:37: 145-156.
Dworkin SF, LeResche L. Research diagnostic criteria for temporoman-
dibular disorders: Review, criteria, examinations and specifications
critique. J Craniomandib Disord 1992;4:301-355.
Ebner FH, Kürschner V, Dietz K, Bültmann E, Nägele T, Honegger J.
Craniometric changes in patients with acromegaly from a surgical per-
spective. Neurosurg Focus 2010:29:e3.
Edwards SP. Computer-assisted craniomaxillofacial surgery. Oral Maxil-
lofac Surg Clin North Am 2010:22:117-134.
El AS, El H, Palomo JM, Baur DA. A 3-dimensional airway analysis of
an obstructive sleep apnea surgical correction with cone-beam com-
puted tomography. J Oral Maxillofac Surg 2011;69:2424–2436.
El H, Palomo JM. Measuring the airway in 3 dimensions: A reliability
and accuracy study. Am J Orthod Dentofacial Orthop 2010;137 S4:
S50 el-e 9.
Enlow DH, Moyers RE. Growth and architecture of the face. J Am Dent
Assoc 1971;82:763-774.
Gateno J, Xia JJ, Teichgraeber JF. New 3-dimensional cephalometric
analysis for orthognathic surgery. J Oral Maxillofac Surg 2011;69:
606–622.
Gerig G, Jomier M, Chakos M. Valmet: A new validation tool for assess-
ing and improving 3D object segmentation. In: Niessen W, Viergever
M, eds. MICCAI 2001: Proceedings of the International Society and
Conference Series on Medical Image Computing and Computer-
Assisted Intervention. Utrecht, Netherlands; Berlin: Springer 2001a:
516–528.
Gerig G, Prastawa M, Weili Lin, Gilmore J. Assessing early brain devel-
opment in neonates by segmentation of high-resolution 3T MRI. Lec-
ture Notes Computer Science LNCS #2879 2003:979-980.
147
Use of 3D Imaging
Gerig G, Styner M, Jones D, Weinberger D, Lieberman J. Shape analysis
of brain ventricles using Spharm. MMBIA Proceedings. IEEE 2001b;
171-178.
Gunz P. Mitteroecker P, Bookstein FL. Semi-landmarks in three dimen-
sions. In: Slice DL, ed. Modern Morphometrics in Physical Anthro-
pology. New York: Kluwer Academic Publishers 2004.
Hajnal JV, Hill DLG, Hawkes DJ, eds. In: Medical Image Registration.
Boca Raton: CRC Press 2001.
Helenius LM, Hallikainen D, Helenius I, Meurman JH, Könönen M,
Leirisalo-Repo M, Lindqvist C. Clinical and radiographic findings of
the temporomandibular joint in patients with various rheumatic dis-
eases: A case control study. Oral Surg Oral Med Oral Pathol Oral Ra-
diol Endod 2005;99:455-463.
Heymann GC, Cevidanes L., Cornelis M, De Clerck HJ, Tulloch JFC.
Three-dimensional analysis of maxillary protraction with intermaxil-
lary elastics to miniplates. Am J Orthod Dentofacial Orthop 2010; 137:
274–284.
Iwasaki T, Saitoh I, Takemoto Y, Inada E, Kanomi R, Hayasaki H, Ya-
masaki Y. Evaluation of upper airway obstruction in Class II children
with fluid-mechanical simulation. Am J Orthod Dentofacial Orthop
2011; 139:e 135-e 145.
Jayaratne YS, Zwahlen RA, Lo J, Cheung LK. Three-dimensional color
maps: A novel tool for assessing craniofacial changes. Surg Innov
2010a; 17:198.
Jayaratne YS, Zwahlen RA, Lo J, Tam SC, Cheung LK. Computer-aided
maxillofacial surgery: An update. Surg Innov 2010b; 17:217-225.
Johnston LE Jr. A few comments on an elegant answer in search of use-
ful questions. Semin Orthod 2011; 17:13-14.
Kapila S, Conley RS, Harrell WE Jr. The current status of cone beam
computed tomography imaging in orthodontics. Dentomaxillofac Ra-
diol 2011:40:24–34.
Katheria BC, Kau CH, Tate R, Chen JW, English J, Bouquot J. Effec-
tiveness of impacted and supernumerary tooth diagnosis from tradi-
tional radiography versus cone beam computed tomography. Pediatr
Dent 2010:32:304-309.
Kim YI, Park SB, Son WS, Hwang DS. Midfacial soft-tissue changes
after advancement of maxilla with Le Fort I osteotomy and mandibu-
lar setback surgery: Comparison of conventional and high Le Fort OS-
148
Cevidanes et al.
teotomies by superimposition of cone-beam computed tomography
volumes. J Oral Maxillofac Surg 2011;69:e225-e233.
Koyama J, Nishiyama H, Hayashi T. Follow-up study of condylar bony
changes using helical computed tomography in patients with tem-
poromandibular disorder. Dentomaxillofac Radiol 2007:36:472-477.
Lenza MG, Lenza MM, Dalstra M, Melsen B, Cattaneo PM. An analysis
of different approaches to the assessment of upper airway morphol-
ogy: A CBCT study. Orthod Craniofacial Res 2010; 13:96-105.
Leung CC, Palomo L, Griffith R. Hans MG. Accuracy and reliability of
cone-beam computed tomography for measuring alveolar bone height
and detecting bony dehiscences and fenestrations. Am J Orthod Den-
tofacial Orthop 2010;137 S4:S109-S119.
Leuzinger M, Dudic A, Giannopoulou C, Killaridis S. Root-contact
evaluation by panoramic radiography and cone-beam computed to-
mography of super-high resolution. Am J Orthod Dentofacial Orthop
2010; 137:389-392.
Lie WN. Automatic target segmentation by locally adaptive image
thresholding. IEEE Trans Med Imaging 1995;4:1036-1041.
Lloyd TE, Drage NA, Cronin AJ. The role of cone-beam computed to-
mography in the management of unfavourable fractures following
sagittal split mandibular osteotomy. J Orthod 2011:38:48–54.
Ma WY, Manjunath BS. Edge flow: A technique for boundary detection
and image segmentation. IEEE Trans Med Imaging 2000;9:1375-
1388.
Maes F, Collignon A, Vandermeulen D, Marchal G, Suetens P. Multi-
modality image registration by maximization of mutual information.
IEEE Trans Med Imaging 1997;16:187-198.
McNamara JA Jr. Studies of adaptation to experimental change in form
and growth of the rhesus monkey. Am J Orthod 1972;62:317–318.
Melsen B. A radiographic craniometric study of dimensional changes in
the nasal septum from infancy to maturity. Acta Odontol Scand 1967;
25:541-561.
Melsen B. Time and mode of closure of the spheno-occipital synchron-
drosis determined on human autopsy material. Acta Anat (Basel)
1972;83:112-118.
Molen AD. Considerations in the use of cone-beam computed tomogra-
phy for buccal bone measurements. Am J Orthod Dentofacial Orthop
2010;137 S4:S130-S135.
149
Use of 3D Imaging
Moon N, Bullitt E, Leemput K, Gerig G. Model-based brain and tumor
segmentation. In: Kasturi R, Laurendeau D, Suen C, eds. Proceedings
16th International Conference on Pattern Recognition ICPR 2002.
IEEE Computer Society 2002:528–531.
Moyers RE, Bookstein FL. The inappropriateness of conventional cepha-
lometrics. Am J Orthod 1979;75:599–617.
Ogawa T, Enciso R, Memon A, Mah JK, Clark GT. Evaluation of 3D
airway imaging of obstructive sleep apnea with cone-beam computed
tomography. Stud Health Technol Inform 2005; 11 1:365-368.
Oh KM, Hong JS, Kim YJ, Cevidanes LS, Park YH. Three-dimensional
analysis of pharyngeal airway form in children with anteroposterior
facial patterns. Angle Orthod 2011;81: 1075-1082.
Orentlicher G, Goldsmith D, Horowitz A. Applications of 3-dimensional
virtual computerized tomography technology in oral and maxillofacial
surgery: Current therapy. J Oral Maxillofac Surg 2010;68: 1933-1959.
Osorio F, Perilla M, Doyle DJ, Palomo JM. Cone beam computed tomo-
graphy: An innovative tool for airway assessment. Anesth Analg
2008; 106:1803–1807.
Palomo J.A. Introduction. Semin Orthod 2011; 17:1.
Paniagua B, Cevidanes L., Walker D, Zhu H, Guo R, Styner M. Clinical
application of SPHARM-PDM to quantify temporomandibular joint
arthritis. Comput Med Imaging Graph 2011a;35;345-352.
Paniagua B, Cevidanes L., Zhu H, Styner M. Outcome quantification us-
ing SPHARM-PDM toolbox in orthognathic surgery. Int J Comput
Assist Radiol Surg 2011b;6:617-626.
Petrovic A. Control of postnatal growth of secondary cartilages of the
mandible by mechanisms regulating occlusion: Cybernetic model.
Trans Eur Orthod Soc 1974:50:69–75.
Popat H, Richmond S. New developments in three-dimensional planning
for orthognathic surgery. J Orthod 2010:37:62-71.
Rohr K. Landmark-based image analysis: Using geometric and intensity
models. In: Computational Imaging and Vision Series. Vol. 21.
Dordrecht, Boston, London: Kluwer Academic Publishers 2001.
Rueckert D, Sonoda LI, Hayes C, Hill DLG, Leach MO, Hawkes DJ.
Nonrigid registration using free-form deformations: Application to
breast MR images. IEEE Trans Med Imaging 1999;18:712-721.
150
Cevidanes et al.
Schendel S.A., Hatcher D. Automated three-dimensional airway analysis
from cone-beam computed tomography data. J Oral Maxillofac Surg
2010;68:696–701.
Schendel S.A, Lane C. 3D orthognathic surgery simulation using image
fusion. Semin Orthod 2009; 15:48–56.
Schendel S, Powell N, Jacobson R. Maxillary, mandibular and chin ad-
Vancement: Treatment planning based on airway anatomy in obstruc-
tive sleep apnea. J Oral Maxillofac Surg 2011;69:663-676.
Schiffman EL, Ohrbach R, Truelove EL, Tai F., Anderson GC, Pan W.
Gonzalez YM, John MT, Sommers E, List T, Velly AM, Kang W,
Look JO. The research diagnostic criteria for temporomandibular dis-
orders: V. Methods used to establish and validate revised Axis I diag-
nostic algorithms. J Orofac Pain 2010a;24:63–78.
Schiffman EL, Truelove EL, Ohrbach R, Anderson GC, John MT, List T.
Look JO. The research diagnostic criteria for temporomandibular dis-
orders: I. Overview and methodology for assessment of validity. J
Orofac Pain 2010b:24:7–24.
Scolozzi P, Terzic A. “Mirroring” computational planning, navigation
guidance system, and intraoperative mobile C-arm cone-beam com-
puted tomography with plat-panel detector: A new rationale in pri-
mary and secondary treatment of midfacial fractures? J Oral Maxillo-
fac Surg 2011;69:1697-1707.
Sera T, Fujioka H, Yokota H, Makinouchi A, Himeno R, Schroter RC,
Tanishita K. Three-dimensional visualization and morphometry of
small airways from microfocal X-ray computed tomography. J
Biomech 2003:36:1587–1594.
Shemesh H, Cristescu RC, Wesslink PR, Wu MK. The use of cone-beam
computed tomography and digital periapical radiographs to diagnose
root perforations. J Endod 2011:37:513-516.
Sherrard JF, Rossouw PE, Benson BW, Carrillo R, Buschang PH. Accu-
racy and reliability of tooth and root lengths measured on cone-beam
computed tomographs. Am J Orthod Dentofacial Orthop 2010;137 S4:
S100-S108.
Solow B. Automatic processing of growth data. Angle Orthod 1969;
39:186-197.
Strauss RA, Burgoyne CC. Diagnostic imaging and sleep medicine. Dent
Clin North Am 2008:52:891-915.
151
Use of 3D Imaging
Styner M, Oguz I, Xu S, Brechbuhler C, Pantazis D, Levitt J, Shenton
ME, Gerig G. Framework for the statistical shape analysis of brain
structures using Spharm-PDM: Special edition open science workshop
at MICCAI. Insight J 2006; 1071:242-250.
Subsol G, Thirion JP, Ayache N. A scheme for automatically building
three-dimensional morphometric anatomic atlases: Application to a
skull atlas. Med Image Anal 1998:2:37-60.
Tai K, Hotokezak H, Park JH, Tai H, Miyajima K, Choi M. Kai LM,
Mishimah K. Preliminary cone-beam computed tomography study
evaluating dental and skeletal changes after treatment with a mandibu-
lar Schwarz appliance. Am J Orthod Dentofac Orthop 2010; 138:
262.e1-.el 1.
Tamimi D, ElSaid K. Cone beam computed tomography in the assess-
ment of dental impactions. Semin Orthod 2009; 15:57-62.
Thompson PM, MacDonald D, Mega MS, Holmes CJ, Evans AC, Toga
AW. Detection and mapping of abnormal brain structure with a prob-
abilistic atlas of cortical surfaces. J Comput Assist Tomogr1997:21:
567–581.
Treil J, Braga J, Loubes JM, Maza E, Inglese JM, Casteigt J, Waysenson
B. 3D tooth modeling for orthodontic assessment. Semin Orthod
2009; 15:42-47.
Truelove E, Pan W, Look JO, MancllA, Ohrbach RK, Velly AM, Hug-
gins KH, Lenton P, Shiffman EL. The research diagnostic criteria for
temporomandibular disorders: III. Validity of Axis I diagnoses. J Oro-
fac Pain 2010:24:35-47.
Tso HH, Lee JS, Huang JC, Maki K, Hatcher D, Miller AJ. Evaluation of
the human airway using cone-beam computerized tomography. Oral
Surg Oral Med Oral Pathol Oral Radiol Endod 2009; 108:768-776.
Tucker S, Cevidanes LHS, Styner M, Kim H, Reyes M, Proffit W, Tur-
vey T. Comparison of actual surgical outcomes and three-dimensional
surgical simulations. J Oral Maxillofac Surg 2010;68:2412-2421.
Van Elslande D, Heo G, Flores-Mir C, Carey J, Major PW. Accuracy of
mesiodistal root angulation projected by cone-beam computed tomo-
graphic panoramic-like images. Am J Orthod Dentofacial Orthop
2010;137 S4:S94-S99.
Yushkevich PA, Piven J, Hazlett HC, Smith RG, Ho S, Gee JC, Gerig G.
User-guided 3D active contour segmentation of anatomical structures:
152
Cevidanes et al.
Significantly improved efficiency and reliability. Neuroimage 2006;
31:11 16-1128.

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154
3D VIRTUAL SURGICAL PLANNING FOR
ORTHOGNATHIC SURGERY
Adriana Da Silveira
ABSTRACT
Complex craniofacial deformities usually involve problems of occlusion, posi-
tion and size of the facial bones as well as soft tissue deficiencies. Surgical cor-
rection involves moving displaced parts to a better position, correcting dental
and skeletal malocclusions and replacing missing parts with new bone or tissue.
In that these problems are in three dimensions (3D), orthognathic surgery in
these cases requires extensive pre-surgical planning. With the advent of cone-
beam computed tomography (CBCT), it now is possible to perform virtual sur-
gery in 3D, creating reliable predictions of patient outcomes. This new technol-
ogy allows clinical transfer to the operating room via CAD/CAM technology
that is used to fabricate surgical splints and cutting guides from the virtual data.
Three examples are presented in which 3D virtual surgical planning was used. In
our experience, this new process has facilitated pre-operative planning as well as
intra-operative execution of the surgical plan with the use of surgical splints and
cutting guides.
KEY WORDS: orthognathic surgery, treatment planning, virtual surgery, CBCT,
orthodontics, craniofacial
INTRODUCTION
Complex craniofacial deformities usually involve problems of
occlusion, position and size of the facial bones as well as soft tissue defi-
ciencies. Surgical correction involves moving displaced parts to a better
position, correcting dental and skeletal malocclusions, and replacing
missing parts with new bone or tissue. Because these problems are in
three dimensions (3D), orthognathic surgery in complex cases requires
extensive pre-surgical planning. With the advent of cone-beam computed
tomography (CBCT) and the development of new computer software
readily and commercially available, it now is possible to perform virtual
Surgery in 3D, creating reliable predictions of patient outcomes. This
approach eliminates problems with current unreliable 2D methods such
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3D Virtual Surgical Planning
as model surgery and 2D cephalometrics for complex 3D problems. This
capability is important particularly in patients with facial asymmetry
where current methods of planning are inadequate (Fig. 1). This new
technology also allows clinical transfer to the operating room via
CAD/CAM technology that was used to fabricate surgical splints and
cutting guides from the virtual data.
New methodology for 3D virtual surgical planning for orthog-
nathic surgery has been described and tested (Gateno et al., 2007; Xia et
al., 2009). In our Craniofacial Center, we employ the Computer-Aided
Surgical Simulation for Orthognathic Surgery (CASS: Xia et al., 2007)
developed by James Xia and Jaime Gateno (The Methodist Hospital,
Houston, TX). Instead of purchasing an expensive software package that
requires an extensive amount of learning time, we opted to work with a
service center that provides the technology and software expertise for a
fee (Medical Modeling Inc., Golden, CO using SimPlant OMS software
developed by Materialise Dental; Fig. 2).
The objective of this chapter is to describe the protocol em-
ployed at Dell Children’s Craniofacial Center along with three illustra-
tive cases of its use. We have been using this new methodology success-
fully in our Craniofacial Center for the past year and have found it to be
an easy process. After a fast learning curve, this approach has become a
reliable and cost-effective way to perform 3D virtual surgical planning.
The advantages of this new methodology are numerous, includ-
ing full 3D visualization of surgical movements and bony structure, thus
increasing the chances of bone union. This approach also helps facilitate
creation of a reliable pre-operative surgical plan, especially for correction
of asymmetries, thus producing better outcomes. This new technology
allows production of cutting templates used intra-operatively that, in
turn, help save time in the operating room. By working with a service
center, there is less time spent learning and using the software (Xia et al.,
2006). Finally, it decreases time spent in the lab making surgical splints
that do not fit.
One of the drawbacks of the traditional method of making splints
by using surgery on plaster dental models is that it simulates the move-
ment of the dental arches only. There is no representation of the 3D
structures that involve the craniofacial complex during this process.
Moreover, traditional methods are unreliable in that reproduction of the pa-
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DaSilveira
Figure 1. Left: Severe facial asymmetry in a young man born with
hemifacial microsomia. Notice microtia of right ear with absence of ear
canal. Right: This anatomical deficiency makes it difficult to fit a tradi-
tional articulator facebow, leading to unreliable reproduction of pa-
tient’s craniofacial anatomy.
Surgical Team
Preoperative Surgical planning
records via webconferencing
| ?
W I
Preoperative visit
and check up
Template and splint
fabrication
Data processing
Figure 2. Schematic of CASS protocol and data flow in preparation for surgery.
SURGERY
tient’s anatomy into an articulator can lead to errors. This drawback is
true particularly in cases of craniofacial syndromes or severe asymmetries
Where reference structures are not always present or in predicted places
(such as external auditory canal) when mounting a facebow for the ar-
ticulator.







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3D Virtual Surgical Planning
Some authors have created different facebow methods to circum-
vent the above-mentioned problems (Quevedo et al., 2011). Another poten-
tial source of error using articulators is the lack of accurate representa-
tion of the anatomy of the condyle and temporal fossa. By using 3D vir-
tual treatment planning, the position of anatomic structures is better visu-
alized better and centric relation remains stable throughout the planning
process.
Nonetheless, there are some deficiencies with this new method-
ology including reliable soft tissue predictions of Surgical changes that
still are not feasible. One example is the amount of upper incisor display
shown pre- and post-operatively. The position of the patient during scan-
ning can affect incisal show (medical CT obtained in supine position as
opposed to CBCT taken with the patient standing). The dynamics of a
Smile cannot be analyzed by a static scan; therefore, most of these deci-
sions on where to position the maxilla vertically need to be performed by
the surgeon pre-operatively as well as during surgery.
Additionally, there is a need for plaster models in the CASS pro-
tocol to complete a 3D virtual model of the patient. Currently there is
lack of accuracy of CT data for fabrication of surgical splints, thus re-
quiring that a set of plaster models are sent to the service center and then
Scanned and superimposed onto the CT data. Moreover, models also
should be sent articulated in a final occlusion and then scanned in this
position to obtain the final occlusion and splint. Virtually there is lack of
collision of CT dental data, meaning that the computer system cannot
stop the images of the surface of the teeth from moving through each
other once they make contact. Therefore, any final occlusion obtained
virtually would be inaccurate. Automated digital dental articulation is
being developed and needs to be validated (Xia et al., 2010).
The accuracy of the software program in producing predictions
and for construction of surgical splints using CAD/CAM technology has
been investigated and found to be adequate compared to conventional
methods of 2D surgical planning with model surgery (Gateno et al.,
2003; Aboul-Hosn Centenero and Hernández-Alfaro, 2011).
METHODS
One of the keys to 3D virtual surgical planning lies in obtaining
records for the creation of a 3D composite skull model that displays bony
structures and teeth accurately. When the patient is ready for surgery, all
orthodontic wires should be passive and coordination of the arches is
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DaSilveira
complete. The patient comes for a pre-operative appointment and records
are obtained including dental impressions, a thorough clinical exam-
ination, 2D photographs, a special bite jig fabrication and Natural Head
Position (NHP) recording using a dental gyroscope (Fig. 3). With the
patient in NHP, the pitch, roll and yaw of the skull are recorded, which
then will be used to reorient the composite skull.
The patient then leaves for a CT scan with the bite jig containing
a facebow attached with fiducial markers (Fig. 3). The patient brings the
bite jig back after the CT scan and the plaster models are checked to
make sure that they fit accurately into the bite jig. The plaster models
then are articulated in a final occlusion and markings are placed in the
models. At this time, all pre-operative records and preliminary plan of
osteotomies are sent to the service center. There, cleaning of all CT data
is performed to eliminate scatter from orthodontic appliances and dental
restorations. The plaster models are scanned and a composite skull model
is created by a combination of 3D CT bone model with a set of digital
models. The model of the skull then is reoriented to NHP and positioned
on the 3D coordinate system. Finally, landmark digitization and cepha-
lometric analysis are obtained, as well as preliminary virtual osteotomies
(as indicated in the preliminary plan) in preparation for virtual planning.
In our Center, surgical planning is accomplished via web meet-
ing with the presence of the multidisciplinary team, including surgeons,
Orthodontist, pediatric dentist, speech pathologist and nurse coordinator (Fig. 4).
CASE REPORTS
We present three examples of cases which 3D virtual surgical
planning was used for treatment planning.
Case 1
A 15-year-old female presented to the Craniofacial Center with a
Class III skeletal and dental malocclusion, an anterior open bite as well
as negative overjet (Fig. 5). After pre-surgical orthodontics prepared her
for orthognathic surgery, records were obtained and sent to the service
center with a preliminary plan of double jaw surgery, including maxillary
advancement and rotation for closure of anterior open bite with a bilat-
eral sagittal split osteotomy (BSSO) of mandible. The web meeting and
planning allowed for better visualization of the changes and the osteoto-
mies using this methodology (Fig. 6). Intermediate and final Surgical
splints were made from the virtual plan.
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3D Virtual Surgical Planning
- - - - - - - - - -
luxºbite
Figure 3. Natural Head Position (NHP) recording using a dental gyro-
Scope. With the patient in NHP, the pitch, roll and yaw of the skull are
recorded. The bite jig contains a facebow with fiducial markers at-
tached that will be used to create a composite 3D skull.
Goſoºeeting Cº-º-º-º-Easy
tº tº on 30 Day-
do-or- ºr----.
-
------ -
----------------
--
----------
--
--------------
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-------------
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-
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º wº-
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Figure 4. Surgical planning done via web meeting with the presence of
the multi-disciplinary team.



160
DaSilveira
Figure 5. Initial facial and intraoral pictures of a 15-year-old female with Class
III skeletal and dental malocclusions, anterior open bite and negative overjet.
Surgery was successful for correction of the deformities and the
patient obtained a favorable final outcome with Class I dental and skele-
tal occlusion and a balanced facial appearance (Fig. 7).
This case could have been planned successfully using current 2D
methodology because only anteroposterior and vertical movements were
performed that did not require extensive planning. The same cannot be
said for cases involving facial asymmetries as these are complex and dif-
ficult to plan in 2D. Therefore, this methodology is useful particularly for
patients such as the one shown below.

| 6 ||
3D Virtual Surgical Planning
Pre operative Intermediate Splint Final Splint
Maxillary impaction ºverlap
| - | Mandible moved into
Advanced LeFort final occlusion
Figure 6. Surgical plan developed after web meeting allowed better visualization
of bony movements and osteotomies. Intermediate and final splints were made
from the virtual plan.
Case 2
A 15-year-old female with Klippel-Feil syndrome and marked
facial asymmetry transferred to our Center for continuation of treatment
(Fig. 8). After pre-surgical orthodontics was completed, records were
obtained and sent to the service center. A preliminary 2D analysis was
performed in our office using Dolphin Imaging (Chatsworth, CA) to eS-
tablish type of surgical procedures and osteotomies (Fig. 9). Notice how
limited this 2D analysis is to plan this complex surgical procedure. After
3D virtual surgical planning was accomplished, a plan was formed that
included maxillary advancement and rotation to the left with mandibular
BSSO for correction of asymmetry and genioplasty. Intermediate and
final splints were obtained from the service center.
The patient underwent surgical procedure as planned minus a
genioplasty. She demonstrated a favorable final outcome with Class I
occlusion with ideal overjet and overbite as well as matching midlines and

162
DaSilveira
Figure 7. Final facial and intraoral pictures, final lateral cephalogram radiograph
post-operative from double jaw surgery after orthodontic appliances were re-
moved. Notice favorable final outcome with a Class I dental and skeletal occlu-
Sion and a balanced final appearance.
correction of bony and teeth asymmetry (Fig. 10). Notice that her soft
tissue still is deficient on the right side after orthognathic surgery. A gen-
ioplasty with fat graft and lip augmentation is being planned for the next
Surgical procedure.
Case 3
A 17-year-old female born with bilateral cleft lip and palate pre-
Sented to our Center with missing upper incisors and, therefore, was
Wearing a removable prosthesis. The patient had two unsuccessful bone
graft surgeries in the past with a significant amount of bone resorption
and was deficient in bone in the pre-maxillary area (Fig. 11).
Surgical planning for a free fibula muscular flap was performed
using 3D software that assisted in the virtual planning. With the help of
Virtual planning, a precise cut of the fibula and precise fit of the pre-
maxillary area were obtained (Fig. 12). This virtual planning allowed for


| 63
3D Virtual Surgical Planning
Figure 8. Initial facial and intraoral pictures of a 15-year-old female with Klip-
pel-Feil syndrome and marked facial asymmetry who transferred to our Center
for continuation of orthodontic treatment. Notice her tilted head position to the
left consistent with a congenital fusion of cervical vertebrae.


164
DaSilveira
Figure 10. Final facial and intraoral pictures of patient post-operatively with
favorable final outcome with Class I occlusion with ideal overjet and overbite as
well as matching midlines and correction of bony and teeth asymmetry. Notice
that her soft tissue still is deficient on the right side after surgery. Genioplasty
with fat graft and lip augmentation is being planned for the next surgical proce-
dure.
an increased chance of bone union and recipient site bone contact. Cut-
ting jigs also were fabricated from the virtual data (Fig. 13). We estimate
that virtual planning saved approximately one to three hours of surgery
time while ensuring a precise fit for the pre-maxillary area and reducing
trauma to the fibula by obtaining the size and cut correctly the first time.
The patient’s reconstruction of the anterior maxilla with free fib-
ula was successful and healed nicely with the skin graft mucosalizing
properly. The patient wore a removable prosthesis while Osseointegrated
implants were inserted (Fig. 14). A healing time of six months is needed
until a final prosthesis can be fabricated substituting her missing upper
incisors. The prosthesis then is connected to the implants, allowing func-
tion and smile to be restored.
* Figure 9. Preliminary 2D analysis performed in our office using Dolphin Im-
Aging to establish type of surgical procedures and osteotomies. Notice how lim-
|ted this 2D analysis is to plan this complex surgical procedure that involves
*Symmetry in all 3D planes.

1.65
3D Virtual Surgical Planning
Figure 11. CT scan and facial pictures of a 17-year-old female
born with bilateral cleft lip and palate with missing upper inci-
sors and large bony deficiency in the pre-maxillary area. The
patient had two unsuccessful bone graft surgeries in the past
with a significant amount of bone resorption.
Figure 12. Surgical planning views of the fibula flap.


166
DaSilveira
º
Figure 13. Cutting jigs were fabricated from the virtual data
that allowed a precise cut of the fibula for a precise fit in the
pre-maxillary area.
DISCUSSION AND CONCLUSION
The potential benefits and actual limits of an integrated 3D vir-
tual surgical planning of patients with craniofacial deformities were dis-
cussed from our experience using our adopted protocol. In our institu-
tion, every orthognathic and craniomaxillary surgery is planned using the
described methodology. In our experience, this new process has facili-
lated the pre-operative planning as well as intra-operative execution of
the surgical plan with the use of surgical splints and cutting guides.
Accurate predictions of bony movements are obtained using this
DeW methodology. Much work still is needed to predict soft tissue
changes resultant from bony movements, especially in complex craniofa-
Cial deformities and facial asymmetries such as in Case 2. Additional
Work in this area has being undertaken by a number of investigators
(Schendel and J acobson, 2009; Cevidanes et al., 2010). The ultimate goal

167
3D Virtual Surgical Planning
- - - -
- -
-
-
-
- - - - -
º - - -
- -
-
- º
º
Figure 14. Final facial and intraoral pictures of patient post-operatively
after reconstruction of the anterior maxilla with free fibula. CT Scan
and radiographs showing osseointegrated dental implants that were in-
serted into the new bone. The patient wore a removable prosthesis
while implants healed.
is to predict the patient’s final facial appearance, thus allowing better
communication with the patient of surgical outcomes.
For the orthodontist, this new methodology allows better com-
munication between providers of the surgical team about the desired out-
comes. The orthodontist can participate in the web meeting from his or
her office, eliminating the need for a face-to-face discussion. All records
are available at the web meeting and decisions about surgical procedures
and final occlusion can be made or modified at the conference, based on
a mutual agreement among providers. Telemedicine is a rapidly develop-
ing application of medicine where medical information is transmitted
through interactive audiovisual media. In the future, it is likely that the
patient may be called to participate at the web meeting to discuss final

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DaSilveira
facial appearance as well as for immediate reference of surgical decisions
Such as Smile dynamics and amount of teeth display.
The use of plaster models may be eliminated in the near future
by either innovations in the software to prevent collision of images, by
dental scanning techniques, or a combination of both. It now is possible
to manipulate virtual study models to predict orthodontic treatment re-
Sults as well as for construction of orthodontic appliances (e.g., Ortho-
CAD, SureSmile, Invisalign). It is likely that in the future other tech-
nologies developed in different fields will be combined to help diagnoses
and treatment planning of the patient as a whole. The art of surgery now
is being transformed into better science. p
REFERENCES
Aboul-Hosn Centenero S, Hernández-Alfaro F. 3D planning in orthog-
nathic surgery: CAD/CAM surgical splints and prediction of the soft
and hard tissues results: Our experience in 16 cases. J Craniomaxillo-
fac Surg 2011 Mar 30 [Epub ahead of print].
Cevidanes LHC, Tucker S, Styner M, Kim H, Chapuis J, Reyes M, Prof-
fit W, Turvey T. Jaskolka M. Three-dimensional surgical simulation.
Am J Orthod Dentofacial Orthop 2010;138:361-371.
Gateno J, Xia JJ, Teichgraeber JF, Christensen AM, Lemoine JJ,
Liebschner MA, Gliddon MJ, Briggs ME. Clinical feasibility of com-
puter-aided surgical simulation (CASS) in the treatment of complex
cranio-maxillofacial deformities. J Oral Maxillofac Surg 2007;65:728-
734.
Gateno J, Xia J, Teichgraeber JF, Rosen A, Hultgren B, Vadnais T. The
precision of computer-generated surgical splints. J Oral Maxillofac
Surg 2003;61:814-817.
Quevedo LA, Ruiz JV, Quevedo CA. Using a clinical protocol for or-
thognathic surgery and assessing a 3-dimensional virtual approach:
Current therapy. J Oral Maxillofac Surg 2011;69:623-637.
Schendel SA, Jacobson R. Three-dimensional imaging and computer
simulation for office-based surgery. J Oral Maxillofac Surg 2009;67:
2107-2114.
Xia JJ, Chang YB, Gateno J, Xiong Z, Zho X. Automated digital dental
articulation. Med Image Comput Comput Assist Interv 2010; 13:278-
286.
169
3D Virtual Surgical Planning
Xia JJ, Gateno J, Teichgraeber JF. New clinical protocol to evaluate cra-
niomaxillofacial deformity and plan surgical correction. J Oral Maxil-
lofac Surg 2009;67:2093-2106.
Xia JJ, Gateno J, Teichgraeber JF, Christensen AM, Lasky RE, Lemoine
JJ, Liebschner MA. Accuracy of the computer-aided surgical simula-
tion (CASS) system in the treatment of patients with complex cranio-
maxillofacial deformity: A pilot study. J Oral Maxillofac Surg 2007;
65:248-254.
Xia JJ, Phillips CV, Gateno J, Teichgraeber JF, Christensen AM, Glid-
don MJ, Lemoine JJ, Liebschner MA. Cost-effectiveness analysis for
computer-aided surgical simulation in complex cranio-maxillofacial
surgery. J Oral Maxillofac Surg 2006;64; 1780-1784.
170
LANDMARKS IN THREE-DIMENSIONAL
IMAGING, DEVELOPMENT AND USAGE
Manuel O. Lagravere Vich
ABSTRACT
Imaging is important in understanding and delivering craniofacial healthcare.
CBCT technology may help overcome the limitations of the traditional imaging
used to quantify three-dimensional (3D) changes produced by orthodontic
treatments. Although 3D volumetric imaging provides images that can be com-
pared to reality in a one-to-one ratio, clinicians tend to analyze them by identify-
ing the structures visually without taking exact measurements or using other
quantitative analysis. Because there is a lack of a validated 3D measuring tool
for the analysis of these types of images, such a tool has to be created and vali-
dated before effective application. The establishment of a precise and reliable
process to analyze images produced by this new technology will give clinicians
new possibilities in determining the changes produced by various controversial
treatments. In this chapter, we mention issues with traditionally used landmarks
in cephalometric analysis when used in CBCT images and then test new land-
marks that could be used in 3D analysis. Superimposition also is discussed and
new possible methods to be used in CBCT images are presented.
KEY WORDS: CBCT, cephalometric analysis, orthodontics, landmarks, superim-
position
INTRODUCTION
Imaging is important in understanding and delivering craniofa-
cial healthcare. Skeletal changes produced from orthodontic treatment
are verified with cephalometric radiographs and dental changes are
evaluated by dental casts and cephalometric radiographs. Both methods
present disadvantages: dental casts are subject to some distortion from
the impression material as well as measurement error, whereas radio-
graphic methods are subject to projection, landmark identification and
measurement errors (Major et al., 1994; Athanasiou, 1995).
171
Landmarks in 3D Imaging
The analysis of human craniofacial patterns first was initiated by
anthropologists and anatomists who recorded various dimensions of an-
cient dry skulls. The first measurements obtained for craniofacial pat-
terns were based on osteological landmarks (craniometry). With time,
measurements were made directly on living subjects using palpation or
pressing the supra adjacent tissue and, finally, with the invention of the
x-rays, measurements were made on cephalometric radiographs (cepha-
lometry; Athanasiou, 1995; Rubin, 1997).
Since the development of cephalometric radiology, numerous
cephalometric analyses have been proposed. They have been useful in
describing how individual patients vary from norms derived from other
studies and also for establishing descriptive communication among clini-
cians (Athanasiou, 1995).
A cephalometric analysis is a two-dimensional (2D) type of di-
agnostic rendering from a three-dimensional (3D) structure. Furthermore,
2D radiographs produce magnification, distortion and superimposition of
adjacent structures. Magnification occurs because the X-ray beams origi-
nate from a point source that is not parallel to all the points of the object
being examined. Distortion occurs because of different magnifications
occurring between different planes. Even though many landmarks used
in cephalometric analysis are located in the midsagittal plane, some
landmarks and many bilateral structures that are useful for the descrip-
tion of craniofacial form are affected by distortion due to their location in
different depth fields (Major et al., 1994; Athanasiou, 1995).
Landmark identification errors also are considered as the major
source of cephalometric error. This type of error is influenced by many
factors such as the quality of the radiographic image, the precision of
landmark definition, reproducibility of the landmark location, the opera-
tor and recording procedure (Major et al., 1994; Athanasiou, 1995). De-
spite all these potential errors, cephalometric radiographs still are used
widely and in many cases are essential in the diagnosis and treatment of
the patient.
Recent developments in imaging have brought many diverse
technologies and approaches. Three-dimensional models of the dentition
can be produced directly or indirectly and 3D craniofacial structural as-
sessment can be accomplished with a new class of volumetric imaging
devices specifically developed for dentistry. An example is the cone-
beam computerized tomography (CBCT) imaging system. This device
makes use of recent technologies including cone-beam principles and
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Lagravere Vich
improved sensors that, when combined with a small chamber volume and
field view, produce 3D images of the craniofacial skeleton at much re-
duced exposure relative to their whole-body CT counterparts used in
medical imaging (Ziegler et al., 2002; Mah and Hatcher, 2003).
Since the mid-1970s, 3D analyses and related procedures in or-
thodontics have been attempted through several different approaches.
The first step in this broad area was the fabrication of 3D models that
imitated oral structures (Chaconas et al., 1976; DeFranco et al., 1976;
Ayala Perez et al., 1980).
Three-dimensional craniofacial imaging requires application of
Various techniques from disciplines such as applied mathematics, com-
puter sciences and statistics (Vannier, 2003). Although several computer
3D methods have been developed to assist orthodontic diagnosis (Beers
et al., 2003; Maki et al., 2003) and others to predict the results of treat-
ment (Baumrind et al., 2003; Meehan et al., 2003; Miller et al., 2003;
Moss et al., 2003), the data obtained presents potential problems in
analysis because few accepted Standards or conventions for managing
this computational data in human jaws exist (Hannam, 2003). Clinical
utilization of these data involves transformation of the information from
3D to 2D format so that the clinician can understand it better. Other
shortcomings are lack of perspective, superimposition effects, imaging
artifacts, information voids and lack of motion (Mah and Hatcher, 2003).
Advances in the use of 3D imaging software have made possible
important changes in the perception of 3D craniofacial structures. CBCT
produces a lower radiation dose than spiral CTs and is comparable to a
full-mouth series of periapical radiographs (Scarfe et al., 2006). It also
allows secondary reconstructions, such as Sagittal, coronal and para-axial
cuts and 3D reconstructions of different craniofacial structures due to its
Volumetric data (Ziegler et al., 2002).
For these reasons, there is a trend in the orthodontic profession to
move from traditional 2D analog films to 3D digital imaging systems. It
is understood by researchers and clinicians that accurate patient informa-
tion would allow the construction of patient-specific models that could
be used for therapeutics, research and education (Mah and Hatcher,
2003).
Compared to the traditional cephalometric radiographs, CBCT
have been reported to produce images that are anatomically true (1 to 1
in size), 3D representations from which slices can be displayed from any
angle in any part of the skull and provided digitally on paper or film.
173
Landmarks in 3D Imaging
Presently, 3D volumetric imaging provides useful information for clini-
cians in identifying teeth and other structures for diagnostic and descrip-
tive purposes (Mah, 2003).
In that this technology was introduced in North America around
2000, the current challenge for the clinician is to understand and interpret
3D imaging and also to decide on a particular imaging modality as a
function of the information/diagnostic yield vs. patient risk and cost
benefit analysis (Mah and Hatcher, 2003). Currently, there is no specific
way to analyze these types of 3D images and interpretation limitations
still exist. For this reason, new standards are required and clinicians need
special training when dealing with these types of images.
CBCT technology may help overcome the limitations of the tra-
ditional imaging used to quantify 3D changes produced by orthodontic
treatments. Although, 3D volumetric imaging provides images that can
be compared to reality in a one-to-one ratio, clinicians tend to analyze
them by just identifying the structures visually without taking exact
measurements or using other quantitative analysis. Because there is a
lack of a validated 3D measuring tool for the analysis of these types of
images, such a tool has to be created and validated before effective ap-
plication. The establishment of a precise and reliable process to analyze
images produced by this new technology will give clinicians new possi-
bilities in determining the changes produced by various controversial
treatmentS.
RELIABILITY OF LANDMARK LOCATION IN LATERAL
CEPHALOGRAMS AND CBCT 3D IMAGES
Magnification and distortion play an important role on the radio-
graphic projection errors of skeletal and dental structures shown in
cephalometric images. Magnification occurs because the x-ray beams
originate from a point source that is not parallel to all the points of the
object examined. Distortion occurs because of different magnifications
occurring between different planes. Although many landmarks used in
cephalometric analysis are located in the midsagittal plane and, therefore,
not prone to superimposition errors, other landmarks representing differ-
ent paramedial structures are affected by distortion due to their location
at different depth fields (Major et al., 1994; Athanasiou, 1995).
Before establishing CBCT as a common orthodontic diagnostic
approach, landmark reliability has to be assessed. The reliability of
landmarks has been evaluated extensively for traditional lateral cephalo-
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grams. However, landmark reliability assessment for CBCT is limited
and additional research is required in this area (Kragskov et al., 1997;
Lou et al., 2007). For this reason, reliability of commonly used land-
marks in cephalometric analysis was determined in lateral cephalograms
and in CBCT images, showing that landmark reliability was high for all
CBCT landmarks and for most of the 2D lateral cephalometric landmarks
(Lagravere et al., 2010a).
Traditional landmarks used in lateral cephalometric analysis
have been defined and used based on what can be visualized on 2D im-
ages. In 3D imaging utilizing CBCT, these traditional landmarks may not
represent useful anatomic structures necessarily. Important structures that
could not be visualized in 2D imaging due to superimpositions now are
available for analysis. New landmarks should be defined and evaluated.
These landmarks now can be located on osseous and dental surfaces or
inside the bone or teeth, depending on the object to be analyzed. Ideal
locations for landmarks in CBCT would be edges, foramina, apexes and
other structures that are pinpointed easily using the tools available in 3D
imaging.
Landmarks that can be viewed easily using 3D reconstruction
and can be verified with 2D slices should be preferred. Other good areas
for landmarks would be location between structures with different densi-
ties eliminating the possibility of being lost during thresholding or dis-
tinguishing the limits between anatomic structures. Furthermore, 3D
landmarks within the cranial base will be unaffected relatively by growth
and will allow superimposition of image sets taken over time independ-
ent of patient positioning (Lagravére et al., 2006). This method will al-
low 3D assessment of craniofacial growth and treatment effects. CBCT
also provides new opportunities for soft tissue landmarks.
In 2D analyses, landmarks have been used in order to represent
structures given the limitations of that type of imaging. With the use of
3D imaging, one landmark may not necessarily represent how a whole
anatomic structure would react to growth or treatment. For this reason,
thought should be given to considering multiple landmarks within a sin-
gle structure of interest. For example, landmarks located on various parts
of a tooth will allow measurement of movement in all planes of space,
including rotational movement.
The establishment of CBCT as a routine orthodontic diagnostic
and treatment evaluation tool still requires development. Secondary
Software applications such as AVIZO require a significant learning curve
175
Landmarks in 3D Imaging
for the typical clinician. There also is a learning curve to understand cra-
niofacial anatomy from 3D imaging and experience is needed to gain
confidence when identifying landmarks.
The use of CBCT or CT overcomes limitations present in tradi-
tional 2D cephalometric analysis where there is overlapping of struc-
tures, giving landmark identification errors that affect determination of
real changes present in maxillary expansion treatments (Goldenberg et
al., 2007; Habersack et al., 2007; Loddi et al., 2008). Several studies
(Garib et al., 2005; Habersack et al., 2007; Garrett et al., 2008; Loddi et
al., 2008) have analyzed 3D changes using CBCTs and CTs in maxillary
expansion treatment. A common factor among all these studies is the use
of only linear and angular measurements instead of using a 3D coordi-
nate system to Verify changes in maxillary expansion treatments in a true
3D format.
Swennen and colleagues (2006a) understood the need of a 3D-
based measurement analysis when using a 3D Cartesian system. They
used conventional 2D cephalometric landmarks to determine a standard-
ized reference position to locate skulls, followed by determining 3D po-
sition changes using different landmarks. The disadvantage of their ap-
proach was the use of landmarks located in skull structures prone to
growth-based changes (landmarks forming the Frankfort horizontal
plane, Sella and Nasion) that could occur concurrently with treatment
changes, thus potentially skewing the results depending on the time of
follow-up.
Tausche and associates (2007) used a similar 3D Cartesian sys-
tem approach to determine changes after maxillary expansion treatments.
The advantage of their approach was the use of landmarks present in the
cranial base to standardize skull position. The study did not reach its full
potential by reporting changes in 3D, however, but instead reported
changes with respect to linear and angular measurements.
Published reliability values with respect to coordinates for land-
marks used in lateral and posteroanterior cephalometrics are not com-
mon. Some studies (Major et al., 1994, 1996; Liu et al., 2000; Kamoen et
al., 2001) reported reliability values for x and y coordinates for several
points used in cephalometrics. One meta-analysis presented an overall
analysis on reliability values for some lateral cephalometric landmarks
(Trpkova et al., 1997). The range of reliability values identified in this
study generally was similar with those reported in other 2D studies. A
tendency found in the studies were that points such as Orbitale, Piriform
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Lagravere Vich
and Porion (in this study known as Auditory External Meatus, or AEM)
showed the largest errors, similar to the results of Trpkova and cowork-
ers (1997).
Based on the results mentioned previously, several factors influ-
encing choice of landmarks in analysis of CBCT images can be identi-
fied. Ideally the landmarks would be identified easily in the 3D images
without the assistance of tomographic slices. Landmarks with small iden-
tification errors are located in areas of high-density contrast with adja-
cent structures and are located on sharply curved or pointed structures.
Landmarks located in the center of a foramen also are good choices.
Landmarks used as superimposition references should be located in non-
growing structures and at a distance from the region being influenced by
treatment to reduce the effect of individual landmark placement.
Ideally several reference landmarks will be chosen that are lo-
cated at a significant distance from each other and in different planes of
space to obtain a 3D coordinate system. Constructed landmarks based on
two distant well-defined landmarks also are useful. Landmarks need to
be identified in the “region of interest” that will be representative of the
structure being evaluated. The landmarks should be identified easily at
any stage of growth and treatment. The choice of these landmarks should
take into account the identification error in the axis of interest. Finally
the choice of landmarks should be customized based on the type of
treatment or growth effects that are being assessed.
The size of the structure being investigated and the magnitude of
change to be detected will influence the clinical significance of landmark
identification error. Landmark identification error may be different in x,
y and z coordinates and some landmarks may be useful for detecting
change in one axis but not in another. Piriform, as an example, has a low
intra-examiner landmark identification error in the transverse dimension
but a high error in the vertical dimension. It may be useful to assess
changes in nasal width in maxillary expansion, but it should be avoided
in assessing vertical change.
New landmarks are available from CBCT imaging that could not
be visualized with traditional 2D imaging. These landmarks would give
us new tools for diagnosis and measurement of growth and treatment
changes and may overcome limitations found in 2D imaging. For exam-
ple, dental pulp chambers can be used to assess 3D changes in tooth posi-
tion. Nerve foramen in the maxilla and mandible (infraorbital foramen,
mental foramen, inferior dental nerve foramen, anterior nasal foramen)
177
Landmarks in 3D Imaging
also are possible choices. The validity of skeletal and dental landmarks to
represent the region of interest would have to be determined, comparing
diagnostic measurements from untreated normal populations to untreated
abnormal populations. Large standard deviations or no difference in
landmark locations between these two different populations would sug-
gest that it is not useful for diagnostic analysis.
Piriform landmarks are located in the outer portion of convexity
of the nasal cavity. The bone in this area is thin and of low density; thus
visualization of this bone is dependent on the threshold used in the soft-
ware (Fig. 1A, B). The apices of some teeth are difficult to visualize due
to low-density contrast with the adjacent bone. The auditory canal is a
cylinder type structure and in the x-axis dimension, AEM could be
placed in a variety of positions along the length of the canal. Zm left and
right are difficult to locate in patients that do not present with a distinct
zygomaxillary notch. Selection of landmarks for use in 3D image analy-
sis should follow certain characteristics.
º B
- -
Figure 1. Piriform anatomic structure in two diffe
threshold. B. Higher threshold.
- - -
rent thresholds. A: LOWer
NEW LANDMARKS TO BE USED IN CBCT IMAGING
AND THEIR USE
Landmark identification errors are influenced specifically by
many factors such as the quality of the radiographic image, landmark
definition, reproducibility of the landmark location, the operator and re-
cording procedure (Major et al., 1994; Athanasiou, 1995). Furthermore
lateral cephalograms are difficult to superimpose accurately because of

178
Lagravere Vich
the difference between the right and left sides, such as difference in scal-
ing ratios, variations in head positioning and overlapping of various cra-
nial structures (Park et al., 2006).
Advances in the use of 3D imaging have improved the visualiza-
tion of 3D craniofacial structures greatly (Mah, 2003). Several computer
3D methods have been developed to assist orthodontic diagnosis (Beers
et al., 2003; Maki et al., 2003) and to predict the results of treatment
(Baumrind et al., 2003; Meehan et al., 2003; Miller et al., 2003; Moss et
al., 2003). Nevertheless, these methods have potential analysis problems
because few accepted standards or conventions for managing computa-
tional data in the maxillofacial complex exist (Hannam, 2003).
Several authors (Seckel et al., 1995; Berkowitz, 1999; Sachdeva,
2001; Ashmore et al., 2002) have stated that superimposition of 3D im-
ages could be an alternative method to analyze changes during and post-
treatment, but this superimposition would depend on the choice of land-
mark locations; the best locations are those located on anatomic surfaces
that are simpler to locate in 3D space (Cevidanes et al., 2005). It is im-
portant to select stable areas, structures as registration points or land-
marks that remain unchanged during orthodontic treatment in order to
make pre- and post-treatment superimpositions (Oliveira et al., 2004).
Defining a standardized coordinate system in which reference points lie
in the cranial base has been proposed with the use of both foramen spi-
nosum (Lagravére and Major, 2005).
Taking this into consideration, some new landmarks that could
not be viewed in traditional x-rays can now be located in CBCTs. Table
1 lists these landmarks and provides a definition for them.
In the case of superimposition, the selection of more reliable and
more anatomically stable landmarks in order to establish a standardized
3D coordinate system is feasible with CBCT. Several authors have re-
ported 3D analysis establishing reference planes in order to locate a 3D
coordinate system inside the skull. Park and colleagues (2006) defined
perpendicular reference planes using left and right porions and orbitales
for the horizontal plane, nasion and pogonion for the sagittal plane and
nasion for the coronal plane. Swennen and associates (2006b) also men-
tioned the use of different planes established with commonly used land-
marks from 2D cephalometry, with the majority located in the facial
skeleton. The disadvantage of these two methods is that the landmarks
chosen to establish reference planes are affected by subject growth or
orthodontic treatment. Por and coworkers (2005) created a reference plane
179
Landmarks in 3D Imaging
Table 1. Definition of landmarks (Lagravere et al., 2011).

Foramen spinosum left (FSL) – geometric center of smallest cir-
cumference with clearest defined borders viewed in axial view on
the foramen spinosum left.
Foramen spinosum right (FSR) – geometric center of smallest
circumference with clearest defined borders viewed in axial view
on the foramen spinosum right.
Ovale left (OvI) – geometric center of smallest oval shape with
clearest defined borders viewed in axial view on the ovale left.
Ovale right (OvK) – geometric center of smallest oval shape with
clearest defined borders viewed in axial view on the ovale right.
Hypoglossal canal left (HyCL) – geometric center of smallest
circumference with clearest defined borders viewed in the sagittal
view of the hypoglossal canal left.
Hypoglossal canal right (HyCR) – geometric center of smallest
circumference with clearest defined borders viewed in the sagittal
View of the hypoglossal canal right.
Rotundum left (RoD) – center lower border of meatus of the left
canal as it enters the cranial fossa.
Rotundum right (RoR) – center lower border of meatus of the
right canal as it enters the cranial fossa.
named biporion-dorsum sellae plane choosing landmarks located in the
cranial base. The drawback with Por’s analysis is that it only establishes
the horizontal plane in a 3D structure.
Growth of the anterior cranial base (excluding frontal bone
thickness) is completed by almost five years of age and is considered a
region of relative anatomic stability (Friede, 1981; Waitzman et al.,
1992; Sgouros et al., 1999). Ricketts (1972) suggested the foramina of
the skull serve as a focal point for gnomonic growth. Foramen rotundum
provides passage for the maxillary nerve, foramen ovale provides pas-
sage for the mandibular nerve and accessory meningeal artery and, fi-
nally, foramen spinosum provides passage for the middle meningeal ar-
tery and recurrent dural branch of the mandibular nerve. These middle
cranial fossa foramina represent the most anatomically stable reference
points in the entire craniofacial complex. These foramina present rea-
sonably regular shaped geometry and CBCT imaging provides the oppor-
180
Lagravere Vich
tunity to use these anatomically stable bilateral structures as reference
points for analysis of craniofacial form and superimposition of serial im-
ages. Furthermore, CBCT is not dependent on head positioning during
image acquisition, which eliminates one of the sources of error of tradi-
tional cephalometrics.
The hypoglossal canal is located in the posterior cranial fossa of
the occipital bone and contains the hypoglossal nerve. The posterior cra-
nial base is displaced posteriorly and inferiorly with growth at the
Spheno-occipital synchondrosis. Posterior cranial base growth follows a
general skeletal rate and continues into adolescence (Ranly, 1980). Based
on the role of neurotrophism, it is likely that the hypoglossal canal will
provide a stable reference within the posterior cranial base and may be
useful for structural remodeling analysis such as the glenoid fossa.
Growth in the width of the posterior cranial base occurs lateral to the hy-
poglossal canal and the distance between the left and right hypoglossal
canals will be stable during adolescent growth. The canal passes almost
horizontally at an anterior-lateral angle to the midsagittal plane.
When analyzing the location of landmarks in the foramina listed
previously, it was found that they present high reliability values and the
definitions (Table 1) make them easier to locate because they all present
different morphologies in 3D (Lagravére et al., 2011).
With these findings, a proposal of a reference point for 3D imag-
ing can be used in 3D cephalometric analysis to fill the gap between the
traditional way of analyzing cephalometric 2D images and analyzing 3D
Volumetric images. This reference point is located in between both fora-
men spinosum and once located, would be the center of the coordinate
system (0,0,0). This point was named ELSA, which presents a high reli-
ability when locating it (Lagravere and Major, 2005).
The use of ELSA as a x = 0, y = 0 and z = 0 reference point in
3D images was done since the location of foramen spinosums were
shown to have a low identification error on both the vertical and horizon-
tal planes (Williamson et al., 1998). This landmark was chosen since it is
a small circle when viewed axially and is easy to locate using the con-
dyle and glenoid fossa as guides. This point also was chosen since pub-
lished literature has demonstrated that most of the cranial base growth (>
85%) occurs in the first five years of age, presenting minor changes after
this age (Friede, 1981; Waitzman et al., 1992; Sgouros et al., 1999).
In traditional 2D cephalometric analyses, superimposition of
cranial base structures is a method to show changes over time associated
181
Landmarks in 3D Imaging
with orthodontic treatment and growth. Although this method has been
used widely, it presents limitations. Errors associated with this type of
superimposition are large enough to have an effect on the interpretation
of data (Baumrind et al., 1976). Furthermore, 2D imaging does not rep-
resent the entirety of a 3D structure. Berkowitz (1999) stated that much
information is lost when 3D structures are assessed through 2D method-
ologies.
A possible method to use CBCT images in determining changes
after treatment or growth is by superimposing images (Seckel et al.,
1995; Berkowitz, 1999; Sachdeva, 2001; Ashmore et al., 2002). Oliveira
and associates (2004) stated that this type of superimposition is challeng-
ing because of the difficulty in selecting stable areas or structures as reg-
istration points or marks that do not change during orthodontic treatment.
The reliability of many 3D-based craniofacial landmarks have been de-
termined (Lagravére et al., 2009, 2010a), but the reliability and accuracy
of 3D superimposition of serial CBCT images using cranial base land-
marks has not been ascertained.
Cranial base landmarks can be identified from CBCT with good
reliability. These landmarks are located in anatomically stable structures
that should not be subject to growth (Friede 1981; Waitzman et al., 1992;
Sgouros et al., 1999) or treatment effects since by five years of age, ×
85% of growth is completed in this area (Baumrind et al., 2003). Fur-
thermore, landmarks are available in different planes of space and, there-
fore, provide potential for a 3D landmark-based superimposition tech-
n1que.
To determine the accuracy and reliability of the method, ELSA
was chosen as the origin to the coordinate system (Miller et al., 2003).
To establish 3D reference planes, three additional non-planar reliable
cranial base landmarks are required. Left and right superior-lateral border
of the external auditory meatus and the dorsal of the foramen magnum
were chosen because they are anatomical structures located in the cranial
base area and in relative correct positions for determining orientation of
planes. The reference plane system eliminates the effect of head position-
ing during image acquisition.
ELSA, both AEM and dorsum foramen magnum (DFM), are
used to form the xy-plane and zy-plane. It should be noted that for the
xy-plane, both AEM are used and intra-reliability for the y- and z-axis
are expected to be greater than that of the x-axis since the AEM is lo-
cated in a cylinder type structure and determining the x-axis location can
182
Lagravere Vich
present some difficulty as it lies along the cylinder long axis. In the case
for the zy-plane, DFM is used and all coordinates were expected to have
high intra-reliability.
To verify if any discrepancies between length measures between
raw data and transformed data were present, lengths were determined
with respect to the center of the reference system (ELSA) to the other
three points forming the coordinate system; values were almost identical.
When integrating a 0.25 mm error into one of the axes of ELSA, the
lengths did present changes of about 1% to DFM, which is the farthest
point to ELSA. This 1% was 0.6 mm of difference between the original
data and the transformed data; thus, we could interpret that for a distance
of approximately 40 mm marker uncertainty could cause an error margin
of + 0.6 mm. This effect is amplified further away from the origin. This
finding should be viewed with caution because as a 0.25 mm error is in-
tegrated into one axis of a landmark, there can be other errors in another
axis and even in other landmarks that can increase the error or cancel the
€ITOr.
When analyzing values obtained in coordinates when errors were
placed intentionally in one axis of ELSA, differences were found in the
coordinates of the other three landmarks with respect to ELSA. By add-
ing a 0.25 mm error in the x-axis of ELSA, one landmark (AEML) pre-
Sented a 1 mm difference from the original value in the y-axis. When
incorporating an error of 1 mm to the x-axis in ELSA, AEMR presented
a 1.9 mm error in the y-axis. These values can be considered large de-
pending on the area of analysis. For example, if these differences were
present on the teeth, since movements of teeth are small in value, this
inherent error could cause misinterpretations. Even if all these points
present high intra-examiner reliability, a difference in the order of 0.25
mm can lead to displacement errors when determining the standardiza-
tion of a reference system.
It also should be noted that when locating any landmarks, the
process will include measurement uncertainty as well as errors in each
coordinate from the true anatomical landmark affecting the transforma-
tion process. Errors may be cumulative or cancel out or amplified at
landmarks further away from the origin, leading to uncertainty about this
method.
To determine if the transformations potentially produce clini-
cally relevant superimposition errors, four reference points located a
maximum distance from the cranial base reference system were ana-
183
Landmarks in 3D Imaging
lyzed. The left and right infra-orbital foramina were chosen to represent
the maxilla, and the left and right mental foramina were chosen to repre-
sent the mandible. Nerve foramen location should be affected minimally
by growth and dental treatment.
Repeated application of the transformation process resulted in
large deviations (2 to 3 mm in some axes in infra-orbital and mental
nerve foramen locations). When the potential envelope of error for the
reference plane system produced by the compounding error of the land-
marks defining the reference points was applied using mathematical
transformation, the error in locating distant landmarks was as high as 25
mm. The four points (ELSA, Auditory External Meatus Left [AEML),
Auditory External Meatus Right [AEMR) and DFM) used for the refer-
ence system nearly were overlapping (largest difference for 0.7 mm in
the x-axis for AEMR). The potential displacement for the coordinates of
these four landmarks ranged from 4 to 6 mm. The change in linear dis-
tance from ELSA to the same landmarks varied from 1.4 to 2.3 mm,
which could be considered to be changed because of growth of the indi-
vidual.
This sensitivity analysis clearly demonstrated that 3D superim-
position of serial CBCT images using four cranial base landmarks is not
an appropriate approach. Although individual cranial base reference
points had a high level of reliability, the small envelope of error for the
individual landmarks had a compound effect in establishing the 3D su-
perimposition reference planes. A potential alternative technique for
CBCT image superimposition is best fit analysis of multiple cranial base
landmarks and computer aided superimposition based on best fit of ob-
ject shapes in the cranial base (Cevidanes et al., 2006). An optimization
analysis is another alternative to use when trying to determine a standard
reference system based on specific landmarks. Future research is needed to
evaluate critically the errors associated with these alternative techniques.
Other new structures that now can be viewed in CBCT imaging
now can be used for landmark location (Table 2).
SEQUENCE OF STEPS TAKEN TOWARD
LANDMARK DETERMINATION
Following a sequence of steps in the area of CBCT image analy-
sis, a method for analysis of these images was tested. The first step was
to determine and compare the reliability of commonly used cephalomet-
ric landmarks obtained from digitized lateral cephalograms with CBCT
184
Lagravere Vich
Table 2. Definition of landmarks (Lagravére et al., 2010b).

Geometric center of the smallest cir-
cumference with defined borders
viewed in axial view on the foramen
spinosum
Foramen spinosum (FS)
Mid-point on a line connecting left and
ELSA right foramen spinosum landmarks
• Center of pulp chamber in molar teeth
Pulp chamber (PC tooth #) • Tip of premolar buccal pulp horn
• Tip of incisor pulp chamber
Mesial buccal apex *
Mesial buccal root apex of molar teeth
(MBA tooth #)
Alveolar bone Outer cortex of alveolar bone at the ver-
(AlB tooth #) tical level of the root apex
Buccal apex (BA tooth #) Buccal root apex of premolars
Apex (A tooth #) - Root apex of incisors
Center of infra-orbitale foramen outer
Infra-orbitale (InfraO) border
Mental (Me) Center of mental foramen outer border
Most posterior border of the pterygoid
lateral plate at the vertical level of the
Lateral pterygoid (LPt) palatal shelves using an axial slice
showing as much of the palate surface
as possible
formatted 3D images. Currently, 3D volumetric imaging provides useful
information for clinicians in identifying teeth and other structures for
diagnostic and descriptive purposes (Mah, 2003). Before establishing
CBCT as a common orthodontic diagnostic approach, landmark reliabil-
ity needed to be assessed. Reliability studies have been performed exten-
sively for traditional lateral cephalograms. Published landmark reliability
assessment for CBCT was limited, however, and additional research was
required in this area (Kragskov et al., 1997; Lou et al., 2007). The results
demonstrated a high reliability for all CBCT landmarks and for most of
185
Landmarks in 3D Imaging
the 2D lateral cephalometric landmarks. Some modifications to landmark
definition and location were necessary in order to adapt them to 3D imag-
ing.
The second step involved the evaluation of suitability of tradi-
tional cephalometric landmarks used to determine changes in orthodontic
treatment in CBCT images. In that CBCT images do not present errors
evident in traditional imaging, it was necessary to evaluate the suitability
of these landmarks. The conclusion of this study (Lagravere et al.,
2010a) was that landmarks selected for 3D image analysis should follow
certain characteristics (i.e., locating them in structures that are identifi-
able easily in CBCT images and are not altered during any phase of
treatment) and modifications in their definitions should be applied since
present definitions include only 2D; thus, incorporation of a third dimen-
sion is needed.
The third step was to evaluate the reliability and accuracy of lo-
cating foramen spinosum, ovale, rotundum and the hypoglossal canal.
This step was undertaken because it is important to select structures that
remain unchanged during orthodontic treatment or growth in order to
obtain possible reference points that could be used to help determine
changes solely due to treatment or growth (Oliveira et al., 2004). Results
showed that the foramen spinosum, foramen ovale, foramen rotundum
and the hypoglossal canal all provided excellent intra-observer reliability
and accuracy. This high level of reliability, along with the fact that they
are present in areas with growth already completed during the treatment
period, make these structures acceptable landmarks to use in establishing
reference systems for future 3D analysis.
The fourth step, once it was established that the previously ana-
lyzed cranial foramina presented high reliability and accuracy, was to
establish a standardized reference point of origin to use in determining
treatment-based anatomical changes with respect to it. This goal was
achieved by using the mid-point between left and right foramen spino-
sum. This arbitrary location was to be used as point (0,0,0) in a standard-
ized coordinate system to measure changes due to growth or treatment in
orthodontic patients. The results of this study demonstrated that the mid-
point between both foramen spinosums (ELSA) presented high intra-
examiner reliability and thus, ELSA was an adequate artificial landmark
to be used as an origin for 3D cephalometric analysis.
After establishing the ELSA origin, the fifth step was to evaluate
two different approaches for analysis of CBCT images. One approach
was to develop a standardized cranial-based coordinate system and the
186
Lagravere Vich
second approach was to use vector lengths between landmarks and
ELSA. With the standardized cranial-based coordinate system, it was
thought that using four reference points to locate a reference system in-
side the cranial base structure would allow superimposition of CBCT
image structures taken at different times during treatment, thus being
able to determine changes of landmarks in the three planes of space (x-,
y- and z-axis separately). If successful, this coordinate system would
help standardize the image orientation plane so that variations in the pa-
tient position when acquiring the image does not play a role in the analy-
sis. The patient position also would not play a role in the analysis in the
Vector measurement method.
Results showed that ELSA, both superior-lateral border of the
AEM and mid-dorsum of foramen magnum points present high intra-
examiner reliability in CBCT 3D images. Thus, it was thought that the
axial-horizontal plane (xy-plane) and Sagittal-Vertical plane (zy-plane)
formed by the respective points used would provide an adequate way to
standardize the orientation of 3D images. Initial evaluation found good
reference plane reliability, but secondary sensitivity analysis identified
that small errors in locating cranial base landmarks had large potential
errors in determining x-, y- and z-coordinates of distance landmarks. It
can be interpreted that errors present in landmarks chosen to standardize
the reference plane can be magnified to points that are farther from these
reference points. An error in one axis could reflect in minor deviations of
the plane, but the farther the region of interest is, the minor deviation
starts increasing. There is a chance that errors in one axis could be can-
celled by an error in another axis or errors in other reference points, but
there also is a chance that these could add up increasing the error present
in the region of interest.
If the four points used to determine the reference planes surround
the region of interest, it would provide a possible solution to reduce these
errors. In a sense, if we have an error of 0.5 mm in one of the reference
landmarks, because it is outside the region of interest, it can be said that
errors found in other landmarks (not related to the reference plane)
would be less. Nevertheless, in this case the reference points are located
in stable anatomical structures that are located posterior to the region of
interest. Unfortunately, no unaffected anatomical structures can be used
to Surround the region of interest to analyze changes due to treatment or
growth.
It should be noted that an error present in one of the vectors used
in obtaining a cross product for the reference system could give a new
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Landmarks in 3D Imaging
vector with a different orientation in space, thus skewing the results. De-
pending on which planes were formed first, an introduction of an error in
the x-axis might affect the y-axis more than other axes. But an error in
the z-axis may affect both the x- and y-axes more. This final result would
depend on the steps of the transformation on whether xy-plane was
formed first or the yz-plane was formed first. The use of cranial base
landmark reference planes for superimposition of serial images of an in-
dividual was rejected.
The final stage consisted in determining new landmarks specific
to 3D imaging. In particular, dental pulp chambers and root apexes were
used to identify dental changes. Alveolar (skeletal) changes were defined
by a landmark intended to approximate the dental root apex movement
with corresponding bony changes. The infra-orbital foramen was tested
as a stable reference point in the maxillary complex and the mental fora-
men was tested as a stable landmark in the mandible. All these land-
marks presented high intra-reliability, making them suitable to measure
changes over time.
FUTURE RESEARCH
Future studies are required to establish a clinically useful ap-
proach for superimposition of serial images of an individual patient. If
this approach can be achieved, positional changes of particular structures
in three planes of space associated with growth and treatment can be de-
fined.
Some work has begun on the development of ways to superim-
pose 3D imaging. One method is using grey Scales to superimpose im-
ages. Cevidanes and associates (2005, 2006) used this style of CBCT
image superimposition to determine treatment changes associated with
orthognathic surgery. Their method consisted of identifying the cranial
base structures in the images. These images later were input into soft-
ware (MIRIT) that computed translation and rotation of these structures
to align them optimally with the use of subvoxel accuracy of the cranial
base (a type of optimization method). What this software did was mask
the maxilla and mandibular structures and only use the cranial base struc-
tures to superimpose. The software compared the grey level intensity of
each voxel in the cranial base in order to obtain a best fit of both images.
After obtaining the superimposition, a different software pro-
gram (VALMET) was used to obtain color-coded differences between
surfaces. This software calculates the 3D Euclidean distance to obtain
188
Lagravere Vich
mean surface distance and quantifies how much on average the two sur-
faces differ from each other, representing these differences with graphi-
cal displays that are color-coded. The reproducibility of the method was
verified comparing measured images of five patients by three independ-
ent evaluators. The results showed 0.26 mm of maximum error by dis-
placement of the mandible and then a qualitative comparison among
color-coded images was done showing that they were similar. Results
obtained were reported only as changes in 2D (e.g., displacement outside
or inside of the mandibular rami and condyles).
The software used for segmentation is available in the public
domain (VALMET software) but MIRIT software must be purchased.
Changes seen after using the software were interpreted only in the sense
of surface distance changes in tendencies (outward or inward) of large
anatomical structures (maxilla and mandible). For this reason, a different
approach was thought through in order to obtain changes in anatomical
structures (whatever their size) and reporting these changes in terms of
each coordinate axis individually.
Kawamata and coworkers (1998) tried to superimpose 3D im-
ages. The images used in this study were obtained from a CT machine.
Their method involved superimposing anatomical structures manually in
order to view condylar displacement after surgery. The steps involved in
this process were to create lateral, axial and frontal 3D CT images of the
pre-and post-operative TMJ region. Then, both lateral images (pre and
post) were superimposed and rotated until anatomic structures such as
the zygomatic arch, mastoid process and infraorbital foramen over-
lapped. This protocol was repeated for the frontal and axial images.
The last step involved the creation of synthetic images where
colors demonstrated the amount of displacement of the condyle. MedVi-
Sion 1.4 software was used in order to determine the changes present. No
reliability of this method has been reported. This method served for the
purpose of their study where visual condyle displacement was deter-
mined. This method, although practical, can present several drawbacks in
that trying to determine coordinate displacements of structures cannot be
accomplished since no reference system has been determined.
Applying this method in growing patients also is difficult be-
cause anatomical structures still are changing and using this method in
the cranial base can be complicated because visualization of these struc-
tures is difficult when only 3D images are analyzed. Although Kawamata
and coworkers (1998) reported quantitative results, they did not apply
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Landmarks in 3D Imaging
any statistical analysis; they stated only rough measurements were taken
because accuracy could not be determined as several factors could influ-
ence their measurement techniques (slice thickness, window level and
width, matrix size and rendering technique). Kawamata and colleagues
(1998) focused more on reporting qualitative changes of the condyles as
anterior or medial displacement, posterior or medial tilting and outward
rotation, but they provided no real sense of the exact amount of condyle
change in each axis after surgery.
Another way to approach superimposition is with the use of an
optimization analysis. This type of analysis involves minimizing the total
mean square root error found over a series of fixed landmark positions, a
best-fit type of analysis. There are many ways of producing optimization
analysis (Maes et al., 1997; Czaplicki, 2008). Cevidanes and colleagues’
(2005) approach involved, in the initial steps, a type of optimization
analysis with the use of MIRIT software. The determination of what
would be the best type of analysis or which way to approach superimpo-
sition still needs to be evaluated. Future work would require establishing
a software program that would involve inserting the coordinates of the
landmarks used to determine the reference system. The software would
calculate the best-fit reference system, superimpose the images and give
coordinate displacements caused solely by growth or treatment in terms
of individual coordinates.
CONCLUSIONS
CBCT has been proven to be an accurate and reliable tool to use
in orthodontics. Nevertheless, much work still is needed to make it the
exam to go to when diagnosing and treating orthodontic patients. New
landmarks and modifications on definitions of traditional 2D landmarks
have been made to make 3D images more useful. Work still is being
done on the superimposition of 3D images and with better quality and
more research, superimposition of 3D images will be easy to do in the
daily orthodontic practice.
REFERENCES
Ashmore JL, Kurland BF, King GJ, Wheeler TT, Ghafari J, Ramsay DS.
A 3-dimensional analysis of molar movement during head-gear treat-
ment. Am J Orthod Dentofacial Orthop 2002;121:18-30.
Athanasiou AE. Orthodontic Cephalometry. London, Baltimore: Mosby-
Wolfe 1995.
190
Lagravere Vich
Ayala Perez C, de Alba JA, Caputo AA, Chaconas SJ. Canine retraction
with J hook headgear. Am J Orthod 1980:78:538-547.
Baumrind S, Carlson S, Beers A, Curry S, Norris K, Boyd RL. Using
three-dimensional imaging to assess treatment outcomes in orthodon-
tics: A progress report from the University of the Pacific. Orthod
Craniofac Res 2003;6 S1; 132-142.
Baumrind S, Miller D, Molthen R. The reliability of head film measure-
ments: 3. Tracing superimposition. Am J Orthod 1976;70:617-644.
Beers AC, Choi W, Pavlovskaia E. Computer-assisted treatment plan-
ning and analysis. Orthod Craniofac Res 2003;6 S1: 117-125.
Berkowitz S. A multicenter retrospective 3D study of serial complete
unilateral cleft lip and palate and complete bilateral cleft lip and pal-
ate casts to evaluate treatment: Part 1. The participating institutions
and research aims. Cleft Palate Craniofac J 1999:36:413-424.
Cevidanes LH, Bailey LJ, Tucker GR Jr, Styner MA, Mol A, Phillips
CL, Proffit WR, Turvey T. Superimposition of 3D cone-beam CT
models of orthognathic surgery patients. Dentomaxillofac Radiol
2005:34:369-375.
Cevidanes LH, Styner MA, Proffit WR. Image analysis and superimposi-
tion of 3-dimensional cone-beam computed tomography models. Am
J Orthod Dentofacial Orthop 2006;129:611-618.
Chaconas SJ, Caputo AA, Davis JC. The effects of orthopedic forces on
the craniofacial complex utilizing cervical and headgear appliances.
Am J Orthod 1976;69:527–539.
Czaplicki A. Optimization solutions depend on the choice of coordinate
system. Acta Bioeng Biomech 2008;10:75-79.
DeFranco JC, Koenig HA, Burstone CJ. Three-dimensional large dis-
placement analysis of orthodontic appliances. J Biomech 1976;9:793-
801.
Friede H. Normal development and growth of the human neurocranium
and cranial base. Scand J Plast Reconstr Surg 1981;15:163–169.
Garib DG, Henriques JF, Janson G, Freitas MR, Coelho RA. Rapid max-
illary expansion: Tooth tissue-borne versus tooth-borne expanders. A
computed tomography evaluation of dentoskeletal effects. Angle Or-
thod 2005;75:548–557.
Garrett BJ, Caruso JM, Rungcharassaeng K, Farrage JR, Kim JS, Taylor
GD. Skeletal effects to the maxilla after rapid maxillary expansion as-
191
Landmarks in 3D Imaging
sessed with cone-beam computed tomography. Am J Orthod Dentofa-
cial Orthop 2008;134:8-9.
Goldenberg DC, Alonso N, Goldenberg FC, Gebrin ES, Amaral TS,
Scanavini MA, Ferreira MC. Using computed tomography to evaluate
maxillary changes after surgically assisted rapid palatal expansion. J
Craniofac Surg 2007; 18:302–311.
Habersack K, Karoglan A, Sommer B, Benner KU. High-resolution mul-
tislice computerized tomography with multiplanar and 3-dimensional
reformation imaging in rapid palatal expansion. Am J Orthod Dento-
facial Orthop 2007;131:776-781.
Hannam AG. Dynamic modeling and jaw biomechanics. Orthod Cranio-
fac Res 2003;6 Sl:59-65.
Kamoen A, Dermaut L, Verbeeck R. The clinical significance of error
measurement in the interpretation of treatment results. Eur J Orthod
2001:23:569-578.
Kawamata A, Fujishita M, Nagahara K, Kanematu N, Niwa K, Langlais
RP. Three-dimensional computed tomography evaluation of postsur-
gical condylar displacement after mandibular osteotomy. Oral Surg
Oral Med Oral Pathol Oral Radiol Endod 1998:85:371-376.
Kragskov J, Bosch C, Gyldensted C, Sindet-Pedersen S. Comparison of
the reliability of craniofacial anatomic landmarks based on cephalo-
metric radiographs and three-dimensional CT scans. Cleft Palate Cra-
niofac J 1997:34:111-116.
Lagravére MO, Carey J, Heo G, Toogood RW, Major PW. Transverse,
vertical, and anteroposterior changes from bone-anchored maxillary
expansion vs. traditional rapid maxillary expansion: A randomized
clinical trial. Am J Orthod Dentofacial Orthop 2010b; 137:304.e301-
e312.
Lagravére MO, Gordon JM, Flores-Mir C, Carey JP, Heo G, Major PW.
Cranial base foramen location accuracy and reliability in cone-beam
computerized tomography. Am J Orthod Dentofacial Orthop 2011;
139:e203-e?10.
Lagravére MO, Gordon JM, Guedes IH, Flores-Mir C, Carey JP, Heo G,
Major PW. Reliability of traditional cephalometric landmarks as seen
in three-dimensional analysis in maxillary expansion treatments. An-
gle Orthod 2009;79:1047-1056.
Lagravére MO, Hansen L, Harzer W, Major PW. Plane orientation for
standardization in 3-dimensional cephalometric analysis with com-
192
Lagravere Vich
puterized tomography imaging. Am J Orthod Dentofacial Orthop
2006; 129:601-604.
Lagravere MO, Low C, Flores-Mir C, Chung R, Carey JP, Heo G, Major
PW. Intraexaminer and interexaminer reliabilities of landmark identi-
fication on digitized lateral cephalograms and formatted 3-
dimensional cone-beam computerized tomography images. Am J Or-
thod Dentofacial Orthop 2010a; 137:598–604.
Lagravere MO, Major PW. Proposed reference point for 3-dimensional
cephalometric analysis with cone-beam computerized tomography.
Am J Orthod Dentofacial Orthop 2005; 128:657-660.
Liu JK, Chen YT, Cheng KS. Accuracy of computerized automatic iden-
tification of cephalometric landmarks. Am J Orthod Dentofacial Or-
thop 2000; 118:535-540.
Loddi PP, Pereira MD, Wolosker AB, Hino CT, Kreniski TM, Ferreira
LM. Transverse effects after surgically assisted rapid maxillary ex-
pansion in the midpalatal suture using computed tomography. J Cra-
niofac Surg 2008; 19:433-438.
Lou L, Lagravére MO, Compton S, Major PW, Flores-Mir C. Accuracy
of measurements and reliability of landmark identification with com-
puted tomography (CT) techniques in the maxillofacial area: A sys-
tematic review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod
2007; 104:402-411.
Maes F, Collignon A, Vandermeulen D, Marchal G, Suetens P. Multi-
modality image registration by maximization of mutual information.
IEEE Trans Med Imaging 1997;16:187-198.
Mah J. 3-dimensional Visualization of Impacted Maxillary Cuspids.
AADMRT Newsletter 2003.
Mah J, Hatcher D. Current status and future needs in craniofacial imag-
ing. Orthod Craniofac Res 2003;6 S1:10-16.
Major PW, Johnson DE, Hesse KL, Glover KE. Effect of head orienta-
tion on posterior anterior cephalometric landmark identification. An-
gle Orthod 1996;66:51-60.
Major PW, Johnson DE, Hesse KL, Glover KE. Landmark identification
error in posterior anterior cephalometrics. Angle Orthod 1994;64:447-
454.
Maki K, Inou N, Takanishi A, Miller AJ. Computer-assisted simulations
in orthodontic diagnosis and the application of a new cone beam x-ray
computed tomography. Orthod Craniofac Res 2003;6 Sl 1:95-101.
193
Landmarks in 3D Imaging
Meehan M, Teschner M, Girod S. Three-dimensional simulation and
prediction of craniofacial surgery. Orthod Craniofac Res 2003;6 S1:
102-107.
Miller RJ, Kuo E, Choi W. Validation of Align Technology's Treat III
digital model superimposition tool and its case application. Orthod
Craniofac Res 2003;6 S1: 143-149.
Moss JP, Ismail SF, Hennessy R.J. Three-dimensional assessment of
treatment outcomes on the face. Orthod Craniofac Res 2003;6 S1:
126-131.
Oliveira NL, Da Silveira AC, Kusnoto B, Viana G. Three-dimensional
assessment of morphologic changes of the maxilla: A comparison of
2 kinds of palatal expanders. Am J Orthod Dentofacial Orthop 2004;
126:354-362.
Park SH, Yu HS, Kim KD, Lee KJ, Baik HS. A proposal for a new
analysis of craniofacial morphology by 3-dimensional computed to-
mography. Am J Orthod Dentofacial Orthop 2006; 129:600.e623-
e634.
Por YC, Barcelo CR, Sng K, Genecov DG, Salyer KE. A novel method
for measuring and monitoring monobloc distraction osteogenesis us-
ing three-dimensional computed tomography rendered images with
the 'biporion-dorsum sellae' plane: Part I. Precision and reproducibil-
ity. J Craniofac Surg 2005;16:430-435.
Ranly DM. A Synopsis of Craniofacial Growth. New York: Appleton-
Century-Crofts 1980.
Ricketts RM. The value of cephalometrics and computerized technology.
Angle Orthod 1972;42:179-199.
Rubin RM. Making sense of cephalometrics. Angle Orthod 1997;67:83-
85.
Sachdeva RC. SureSmile technology in a patient-centered orthodontic
practice. J Clin Orthod 2001:35:245-253.
Scarfe WC, Farman AG, Sukovic P. Clinical applications of cone-beam
computed tomography in dental practice. J Can Dent Assoc 2006;72:
75-80.
Seckel NG, van der Tweel I, Elema GA, Specken TF. Landmark posi-
tioning on maxilla of cleft lip and palate infant: A reality? Cleft Palate
Craniofac J 1995:32:434–441.
Sgouros S, Natarajan K, Hockley AD, Goldin JH, Wake M. Skull base
growth in childhood. Pediatr Neurosurg 1999;31:259-268.
194
Lagravere Vich
Swennen GR, Schutyser F, Barth EL, De Groeve P, De Mey A. A new
method of 3-D cephalometry: Part I. The anatomic Cartesian 3-D ref-
erence system. J Craniofac Surg 2006a, 17:314-325.
Swennen GRJ, Schutyser F, Hausamen J-E. Three-dimensional Cepha-
lometry: A Color Atlas and Manual. Berlin, New York: Springer
2006b.
Tausche E, Hansen L, Hietschold V, Lagravére MO, Harzer W. Three-
dimensional evaluation of surgically assisted implant bone-borne
rapid maxillary expansion: A pilot study. Am J Orthod Dentofacial
Orthop 2007;131:S92-S99.
Trpkova B, Major P, Prasad N, Nebbe B. Cephalometric landmarks iden-
tification and reproducibility: A meta analysis. Am J Orthod Dentofa-
cial Orthop 1997; 112:165-170.
Vannier MW. Craniofacial imaging informatics and technology devel-
opment. Orthod Craniofac Res 2003;6 S1:73–81.
Waitzman AA, Posnick JC, Armstrong DC, Pron GE. Craniofacial skele-
tal measurements based on computed tomography: Part II. Normal
values and growth trends. Cleft Palate Craniofac J 1992:29:118-128.
Williamson PC, Major PW, Nebbe B, Glover KE. Landmark identifica-
tion error in submentovertex cephalometrics: A computerized method
for determining the condylar long axis. Oral Surg Oral Med Oral
Pathol Oral Radiol Endod 1998;86:360-369.
Ziegler CM, Woertche R, Brief J, Hassfeld S. Clinical indications for
digital volume tomography in oral and maxillofacial surgery. Den-
tomaxillofac Radiol 2002:31:126–130.
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196
GINGIVAL CREVICULAR FLUID AS A SOURCE
OF BIOMARKERS OF PATIENT
RESPONSIVENESS TO ORTHODONTIC
TREATMENT
Giuseppe Perinetti, Luca Contardo, Tiziano Baccetti
ABSTRACT
Identification of skeletal maturation phases is of primary importance in terms of
individual responsiveness to nearly all dentofacial orthopedic treatments. Stud-
ies are being performed to evaluate whether the gingival crevicular fluid (GCF)
alkaline phosphatase (ALP) activity in growing subjects reflects the stages of
individual skeletal maturation. In one such investigation, 85 healthy growing
Subjects were enrolled according to a double-blind, prospective, cross-sectional
design. Samples of GCF were collected from each subject at the mesial and dis-
tal sites of both of the central incisors in both the maxillary and mandibular den-
tal arches. The skeletal maturation phase in each subject was defined according
to the improved cervical vertebra maturation (CVM) method at six cervical
stages (CS); the dentition phases also were recorded. The relationship seen be-
tween the GCF ALP activity and the CVM stage was significant. In particular,
there was a two-fold peak in enzyme activity at the pubertal stages (CS3 and
CS4), as compared to the pre-pubertal stages (CS1 and CS2) and post-pubertal
stages (CS5 and CS6), at both the maxillary and mandibular sites. No significant
differences were seen according to gender or between the maxillary and man-
dibular locations. Subsequently, the circumpubertal dentition phases and chrono-
logical ages also were evaluated for potential correlations with GCF ALP activ-
ity as a biomarker of skeletal maturation; however, neither correlated signifi-
cantly with this enzymatic activity. While circumpubertal dentition phase and
chronological age cannot be considered as reliable indicators of skeletal matur-
ity, as an adjunct to the standard methods based upon radiographic parameters,
the GCF ALP represents a non-invasive clinical biomarker for identification of
the pubertal growth spurt in periodontally healthy subjects scheduled for ortho-
dontic treatment.
KEY WORDS: biomarkers, gingival crevicular fluid (GCF), skeletal maturation,
diagnosis, treatment timing
197
Gingival Crevicular Fluid
GINGIVAL CREVICULAR FLUID (GCF) AS A SOURCE
OF BIOMARKERS
Origin and Composition of GCF
The gingival crevicular fluid (GCF) emerges from between the
surface of the tooth and the epithelial integument, a fluid that initially
was described over a century ago by dental pioneer GV Black (1899).
However, the exact nature of the fluid, its origins and its composition
remained controversial for decades.
Continuous GCF flow might have physically protective effects
through the flushing of the gingival crevice, as well as facilitating the se-
cretion and delivery of immunoglobulins (Brill, 1959a). GCF has been
shown to be derived from the epithelium lining of the gingival pocket
(Brill and Bjom, 1959); its flushing effects were demonstrated through
the removal of carbon particles and bacteria that previously had been in-
troduced into the gingival crevice (Brill, 1959b).
The most commonly accepted theory of GCF formation arose
from the hypotheses of Pashley (1976) and Alfano and colleagues
(1976). They suggested that the initial fluid produced would be simply an
interstitial fluid that appears in the crevice as a result of an osmotic gra-
dient (Fig. 1). This fluid thus would be considered as a transudate. Sub-
sequently, upon local inflammation or injury, the GCF would become an
inflammatory exudate.
Investigations into the protein content of the GCF reported that
in healthy gingival crevices, the GCF has a protein concentration similar
to that of interstitial fluid, which notably was lower than that of serum
(Bang and Cimasoni, 1971; Curtis et al., 1988). On the contrary, the in-
flamed gingiva has GCF with raised protein concentrations that are simi-
lar to those of serum (Curtis et al., 1988). Indeed, a strong co-variation
between the proteins studied in these two fluids suggested that GCF is an
inflammatory exudate of serum (Tollefsen and Saltvedt, 1980).
The range of the GCF constituents is large, as it can contain
both human and bacterial cells and many different molecules. For in-
stance, among the most representative cellular components of the GCF,
there are leukocytes and especially neutrophils, which have important
roles in the antimicrobial defense of the periodontium (Delima and Van
Dyke, 2003). However, when dealing with periodontal patients, while the
bacterial and cellular components of the GCF are of primary concern to
clinicians and researchers, its molecular contents represent a promising
198
Perinetti et al.
Gingiva
Blood vessel
Figure 1. Gingival crevicular fluid (GCF) forma-
tion. GCF flow (grey arrows) is an interstitial
fluid which appears in the crevice as a result of
an osmotic gradient.
Source of biomarkers in orthodontics for the monitoring of both site-
Specific tissue remodeling that is incident to tooth movement (Kavadia-
Tsatala et al., 2002) and, as revealed more recently, skeletal maturation
On an individual basis (see below).
The host molecular content of the GCF includes a large variety
of molecules that, according to their specific biological functions, have
the potential to be classified as biomarkers of
1. Cell death;
2. Tissue damage:
3. Inflammation;
4. Bone resorption;
5. Bone deposition; and
6. Others (see Table 1).



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Gingival Crevicular Fluid
Table 1. Main GCF biomarkers according to biological significance.
For more details, see reviews in Periodontology 2000 (Uitto, 2003).
1. Biomarkers of cell death
Aspartate aminotransferase
Lactate dehydrogenase
2. Biomarkers of tissue damage
Hydroxyproline
Collagen cross-linking peptides
Glycosaminoglycans
3. Biomarkers of inflammation
Cytokines (interleukins, tumor necrosis factors, interferons, growth
factors, colony-stimulating factors)
Arachidonic acid derivates (prostaglandins, leukotrienes)
Neutrophil alkaline phosphatase (ALP)
4. Biomarkers of bone resorption
Osteonectin
Bone phosphoprotein
Osteocalcin
Cross-linked carboxyterminal telopeptide of type I collagen
Receptor activator of nuclear factor kappa-B and its ligand
5. Biomarkers of bone deposition and mineralization
Bone ALP
Osteoprogeterin
6. Other biomarkers
Metalloproteases (proteolytic enzyme)
Cathepsin B (proteolytic enzyme)
Antibodies
For several of these biomarkers, associations between their lev-
els and specific clinical conditions have been shown, along with the
predictive value for the biomarkers, e.g., in terms of tissue destruction
due to periodontitis (Persson et al., 1990). Among these biomarkers,
those related to bone deposition, such as bone ALP (Ishikawa and
Cimasoni, 1970), are promising candidates as useful clinical biomarkers
in orthodontics (Insoft et al., 1996; Perinetti et al., 2002).

200
Perinetti et al.
COLLECTION OF CREVICULAR FLUID
The GCF can be collected by several methods, each of which has
its own advantages and disadvantages. The most used and studied are:
1. Gingival washing;
2. Capillary tubing; and
3. Absorbent filter paper strips.
These are listed in Table 2 according to their main advantages and disad-
Vantages.
Table 2. Comparisons of the collection methods for GCF.

Method Advantages Disadvantages
Gingival Undetermined dilution of GCF
washing Recovery of cells Possible loss of GCF during aspiration
Capillary Long time (30 min)
tubing Exact volume determination Damage to tissues
Easy and rapid (30-60 s)
Paper strips Least traumatic Errors in determination of GCF volume
Gingival Washing
This technique was described over three decades ago (Skapsi and
Lehner, 1976), whereby the gingival crevice is perfused with a predeter-
mined volume of an isotonic solution. For instance, several ml of Hanks’
balanced salt solution can be instilled into and re-aspirate from the gingi-
Val crevice at the interdental papilla. The fluid collected then represents a
dilution of the GCF and will contain both cells and soluble constituents,
such as plasma proteins. As a major disadvantage, this procedure can fail
to recover all of the instilled fluid or the GCF contents during re-
aspiration. Also, precise estimations of the volume of the GCF collected
are not possible. This procedure is preferred when the cells in the gingi-
Val crevice have to be collected.
Capillary Tubing
In this collection method, which initially was described 40 years
ago by Sueda and colleagues (1969), capillary tubes of known internal
diameter are inserted into the crevice and left in situ to allow the GCF to
be collected by capillarity. Due to the known internal diameter of the cap-
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Gingival Crevicular Fluid
illary tubes, it is possible to determine the exact GCF volume collected,
through the measurement of the distance that the GCF has migrated
along the capillary tubing. This method, therefore, is used when undi-
luted GCF samples are needed, along with the precise determination of
the volume collected. On the other hand, the use of capillary tubing re-
quires relatively long periods of time for sampling adequate GCF quanti-
ties (except when dealing with inflamed tissues), as this procedure can
last for up to 30 minutes, making the capillary holding difficult and pos-
sibly traumatic for tissues. This intervention in turn can cause the release
of serum-derived fluid that will alter the volume and composition of the
original GCF (Lamster et al., 1985). A further disadvantage of this
method is the difficulty associated with the removal of the full GCF
sample from the capillary tubes.
Absorbent Filter Paper Strips
The use of adsorbent paper strips now represents the procedure
most used in GCF collection (Lamster et al., 1985; Persson et al., 1990;
Perinetti et al., 2002). In this procedure, absorbent paper strips (either
endodontic paper points or dedicated strips for GCF collection [PeioPa-
pers, Oraflow Inc., NY]) are inserted into the gingival crevice and left in-
situ for 5 to 60 seconds to allow the GCF to be adsorbed by the paper
(Fig. 2). This procedure has the advantage of being quick and easy, and
also the least traumatic.
Diverse modes of insertion, collection time and number of re-
peated samplings at the same sites give this procedure great versatility
for different purposes. On the other hand, because of this methodological
variability, the data from different studies need to be interpreted with
caution, taking into account how exactly the collection of the GCF was
performed with these paper strips. For instance, the paper strips can be
inserted just into the entrance of the gingival crevice (Perinetti et al.,
2002) or the periodontal pocket (Löe and Holm-Pedersen, 1965), or they
can be inserted to the base of the pocket or until “minimum resistance” is
felt (Brill, 1962).
GCF: VOLUME v.S. FLOW
An important concept to be considered is the collection proce-
dure used for the GCF (Griffiths, 2003). This use of paper strips allows
the resting GCF inside the crevice to be collected, which is referred to as
the GCF volume. In contrast, the use of capillary tubing kept inside the
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Perinetti et al.
Figure 2. Collection of the GCF using PerioPapers.
crevice for several minutes is useful for the measurement of the rate of
flow of the GCF, which is a different entity.
Previous evidence has shown differential behaviors of the GCF
Volume and flow rate under gingival inflammation (Persson and Page,
1990; Griffiths et al., 1992). In particular, only the GCF flow rate ap-
pears to increase during clinically detectable gingival inflammation,
While the GCF volume appears to be less responsive to the actual clinical
condition (Persson and Page, 1990; Griffiths et al., 1992).
An interesting example is seen by the differential effects of or-
thodontic tooth movement on the GCF volume and flow rate under clini-
cally healthy periodontal conditions. Indeed, while the GCF volume (col-
lected by paper strips) does not appear to be influenced by orthodontic
tooth movement (Drummond et al., 2011), the GCF flow (collected by
Capillary tubes) has been reported to increase during orthodontic treat-
ment (Samuels et al., 1993). Finally, the GCF flow also can be measured
by paper strips, according to a repeated sampling procedure, with use of
up to four or five paper strips at the same site, where the first strip either
is analyzed separately (Chapple et al., 1996) or pooled with the others
(Lee et al., 2004).
Apart from the quantity of the GCF, the composition of the GCF
collected also can change according to the collection time. For instance,
When prolonged periods of collection by capillary tubes are used (e.g., 20
minutes or more), the protein concentrations of the GCF collected tends
to become similar to those of the serum, rather than to those of the inter-
Stitial fluid (Curtis et al., 1988). Therefore, knowledge of the GCF col-
lection method also has importance in terms of the biological signifi-
Cance of the samples taken (i.e., quality and quantity).

203
Gingival Crevicular Fluid
GCF CONSTITUENTS:
TOTAL CONTENT vs. CONCENTRATIONS
The constituents within GCF samples can be expressed as abso-
lute amounts (pug/sample), total activity (units [UI/sample) or concentra-
tions (pg/ul or U/ul). A study comparing four methods of data analysis
for lysosomal enzyme activities in GCF indicated that because of the in-
herent problems of accurate determination of the GCF Volume, the use of
concentrations was not an appropriate method for data presentation
(Lamster et al., 1988).
A further investigation of the diagnostic potential of GCF alka-
line phosphatase (ALP) activity as a predictor of periodontal attachment
loss during periodontitis (Chapple et al., 1999) showed that only the total
enzyme activity and not the concentrations gave a satisfactory perform-
ance. Therefore, the total contents instead of concentrations of the GCF
constituents should be used for data expression of these biomarkers to
maintain diagnostic reliability.
Other Aspects Related to Collection and Manipulation of GCF
Contamination. The major sources of contamination of GCF
samples would be blood, saliva or plaque. The presence of dental plaque
on the paper strips used for collecting GCF can have large influences on
the volumes recorded (Stoller et al., 1990). Careful isolation also should
be performed to minimize the potential for saliva contamination. Appli-
cation of the assay to Saliva samples collected using good isolation and
drying techniques has confirmed that the likelihood of significant contri-
butions from saliva would not be significant.
GCF Volume Determination. To quantify the GCF volume col-
lected using paper strips, a dedicated instrument was developed: the Pe-
riotron (versions 600, 6000 and 8000; Chapple et al., 1995; Ciantar and
Caruana, 1998). However, volumes of less than 0.2 pil can cause prob-
lems due to evaporation (Chapple et al., 1995). Furthermore, the use of
the Periotron requires special attention, because of the need for repeated
calibration, as its readings can vary with room temperature and relative
humidity (Ciantar and Caruana, 1998). Moreover, it has been reported
that differences in the protein content of the calibration fluid can affect
the volume measures obtained significantly (Ciantar and Caruana, 1998).
As a further limitation, the calibration of the Periotron 8000 only
appears to be consistent over a one-week interval (Ciantar and Caruana,
1998). The potential for sample loss onto the surface of the Periotron
204
Perinetti et al.
plates during measurement and the time required to obtain a reading also
have been described as inconvenient when using the Periotron (Medlicott
et al., 1995).
PATIENT RESPONSIVENESS TO ORTHODONTIC
TREATMENT AND TREATMENT TIMING
Growth and Responsiveness to Treatment
Information on growth trends in patients with different skeletal
malocclusion is needed for both effective treatment and reasonable ex-
pectations in terms of stability of treatment outcomes. Indeed, human
growth and development are not uniform, with accelerations and
decelerations in the growth velocity of different skeletal components at
Various developing maturational stages, i.e., skeletal maturation or
growth phase (Greulich and Pyle, 1959; Björk and Helm, 1967; Fishman,
1979; Petrovic et al., 1990; Franchi et al., 2000; Baccetti et al., 2005).
Regarding implications clinically, the timing of treatment onset
can be as critical as the selection of the specific treatment protocol (Pet-
rovic et al., 1990; Baccetti et al., 2005; Cozza et al., 2006). In growing
Class II patients, the amount of supplementary mandibular growth in-
duced by functional appliances appears to be significantly greater when
the functional treatment is performed during the pubertal growth spurt
(Petrovic et al., 1990; Cozza et al., 2006). Orthopedic treatment of pa-
tients with Class III malocclusion (Franchi et al., 2004) and rapid maxil-
lary expansion (Baccetti et al., 2001), on the other hand, also benefits
from the identification of optimal timing to achieve maximum efficacy,
which in these cases is at a pre-pubertal growth phase. Therefore, the
correct identification of the different phases of skeletal maturation repre-
Sents a crucial issue in orthodontic diagnosis and treatment planning.
Evidence of the impact of correct treatment timing and its influ-
ence on the efficiency of treatment arises when dealing with the treat-
ment of skeletal Class II malocclusions. For these malocclusions, con-
trolled clinical trials have reported supplementary mandibular growth
(measured as Condylion-Gnathion or Condylion-Pogonion distance) over
untreated matched controls, as around 2 mm and 4 mm for patients
treated before (early) or during (late) their pubertal growth spurt, respec-
tively (Fig. 3, overall effects).
Therefore, identification of skeletal maturity, with particular re-
gard to the onset of the pubertal growth spurt, has major clinical implica-
205

Gingival Crevicular Fluid
Study Timing Difference in means (95% CI) Appliance Duration
Baccetti et al., 2000 Late – H. Twin-block 17 months
Faſtin et al., 2003 Late Bionator 28 months
Franchi et al., 1999 Late | — H Herbst 12 months
Overall Late O-
Tullochet al., 1997 (a) Early Bionator 15 months
Baccetti et al., 2000 Early - - Twin-block 14 months
Faſtinet al., 2003 Early ---- Bionator 22 months
O'Brien et al., 2003 Early — — Twin-block 15 months
De Aemidaetal, 2005 Early | - Herbst 12 months
Overall Early ()
m of supplementary growth
2 5 2. A 5 §
Favours control Favours treated ".
Figure 3. Supplementary mandibular growth (mm) following functional treat-
ment in Class II patients according to timing of treatment. Supplementary man-
dibular growth reported as Condylion-Gnathion or Condylion-Pogonion dis-
tances. The timing of treatment is defined as late (during pubertal growth spurt)
or early (before onset of pubertal growth spurt). The data are reported as annual-
ized changes. Overall supplementary growth of the mandible as mean (95% con-
ſidence interval): 40 mm (2.8 to 5.3 mm) and 1.4 mm (1.0 to 1.8 mm) for the
late and early treatment timing, respectively.
tions when dealing with orthodontic treatment in growing subjects, espe-
|
cially when skeletal disharmonies are present (Hägg and Pancherz, 1988:
Petrovic et al., 1990; Baccetti et al., 2005). For this reason, several indi-
cators of skeletal maturity have been investigated over the last five dec-
ades. Among these indices, there have been the dentition phase (Nanda.
1960, Björk and Helm, 1967; Franchi et al., 2008), dental maturation
(Demirian et al., 1985; Perinetti et al., 2011b) and chronological age
(Björk and Helm, 1967; Fishman, 1979; Petrovic et al., 1990; Baccettie!
al., 2006), which all have shown poor diagnostic performance. The most
reliable indices have been radiography-based, hand-wrist analysis
(Greulich and Pyle, 1959, Hägg and Pancherz, 1988) and the improved
cervical vertebral maturation (CVM) method (Baccetti et al., 2005).
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Perinetti et al.
The Improved CVM Method
The improved CVM method (Baccetti et al., 2005) is useful par-
ticularly when skeletal maturity has to be assessed on a single cephalo-
gram and only the cervical vertebrae from the second to the fourth are
visible. The CVM method has the further advantage of being assessed on
the lateral cephalogram, which is the radiographic record that is used
routinely for orthodontic diagnosis and treatment planning, with no need
for additional x-ray exposure. The CVM method comprises six stages
(CS1-CS6) of cervical vertebral maturation (Fig. 4). Briefly, these are
defined as:
cstics2 css ics4; css css
A \\\\\\\
* | * : * * * * * * *
* : * : * * * * * * *
Figure 4. Vertebral maturation according to the improved CVM method.
1. CS1: when the lower borders of the second, third and
fourth vertebrae (C2, C3 and C4) are flat and the bod-
ies of C3 and C4 are trapezoid in shape. CS1 occurs
at least two years before the pubertal growth spurt.
CS2: when only the lower border of C2 is concave
and the bodies of C3 and C4 are trapezoid. CS2 oc-
curs one year before the growth spurt.
3. CS3: when the lower borders of both C2 and C3 have
concavities and the bodies of C3 and C4 are either
trapezoid or rectangular horizontal in shape. CS3
marks the ascending portion of the growth spurt.
4. CS4 when the lower borders of C2 to C4 have con-
cavities and the bodies of both C3 and C4 are rectan-
gular horizontal in shape. CS4 marks the descending
portion of the growth spurt.
2.


207
Gingival Crevicular Fluid
5. CS5: when the lower borders of C2 to C4 have con-
cavities and at least one of the bodies of C3 and C4 is
square. CS5 occurs one year after the growth spurt.
6. CS6: when the lower borders of C2 to C4 have
concavities and at least one of the bodies of C3 and
C4 is rectangular vertical in shape. CS6 occurs at
least two years after the growth spurt.
Biomarkers of Skeletal Maturation
While the current indices of skeletal maturation are morphologi-
cal, new possibilities might be offered through biochemical markers.
Such biomarkers avoid radiographic exposure and represent agents that
are involved directly in bone growth and remodeling. The scarce data re-
ported to date include molecular constituents from the serum, such as IGF-I
(Masoud et al., 2008). More recently, on the basis of serum ALP in-
creases during puberty (Szulc et al., 2000) that are concomitant to the
mandibular growth spurt (Baccetti et al., 2005), a prospective, double-
blind study evaluated GCF ALP activity in growing subjects in relation
to their stages of individual skeletal growth, as recorded through the
CVM method (Perinetti et al., 2011a). This study ultimately proposes
GCF ALP activity as a non-invasive biomarker of individual skeletal
maturation in orthodontic patients.
THE EXPERIMENTAL STUDY
Study Population and Design
This study enrolled consecutive subjects seeking orthodontic
treatment who had not been treated previously (< 18 years). Signed in-
formed consent was obtained from the parents of the subjects prior to en-
try into the study, and the protocol was reviewed and approved by the
Ethical Committee of the University of Trieste, Italy. The following en-
rolment criteria were observed:
1. Age between 7 and 18 years;
2. Intermediate or late mixed, or early permanent phases
of dentition;
3. Good general health, with absence of any nutritional
problems;
4. No use of anti-inflammatories or antibiotics in the
month preceding entry to the study;
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Perinetti et al.
5. Probing depth values not exceeding 4 mm for the
whole dentition and 3 mm for the anterior sextants;
and
6. Full-mouth plaque score (FMPS) and full-mouth
bleeding score (FMBS) < 25%.
The subjects were scheduled for enrollment at their first clinical
examination; subsequently, during a second visit seven to ten days before
to GCF collection, they underwent a session of professional supragingi-
Val and subgingival scaling and also received repeated oral-hygiene
instructions. Moreover, over the days between the professional scaling
and the GCF collection, the subjects were asked to rinse their, mouths
twice per day with 0.012% chlorhexidine mouthwash and were not
allowed to take any anti-inflammatories or antibiotics. At the last clinical
session, when the GCF was collected for ALP activity determination,
their clinical parameters were recorded, with dental panoramic
radiographs and lateral cephalograms taken immediately after GCF
*}ver 90 subjects were screened, out of which 85 were enrolled
in the study: 51 females and 34 males (mean age, 11.7 + 2.3 years; range,
7.7 to 16.9 years). The data for the CVM staging was available in 72 of
these subjects: 45 females and 27 males.
Assessment of Individual Skeletal Maturity and Dentition Phase
Assessments of skeletal maturity were carried out through the
CVM method on lateral cephalograms (Fig. 4). Assessments of the denti-
tion phase were carried out according to the following definitions
(Franchi et al., 2008):
1. Intermediate mixed dentition, when the permanent in-
cisors and first molars have erupted fully, with the
presence of deciduous teeth in the posterior region
(deciduous canine and first and second deciduous mo-
lars);
2. Late mixed dentition, when any of the deciduous ca-
nines and molars exfoliated, with eruption of any
permanent canines and premolars; and
3. Early permanent dentition, when all of the permanent
teeth are present (possible presence of second molars;
absence of third molars).
209
Gingival Crevicular Fluid
These assessments of the phases of dentition were performed by a single
operator by intraoral evaluation, as well as on dental casts and dental
panoramic radiographs when needed.
Clinical Monitoring and GCF Collection
The intraoral clinical examinations were performed on four sites
on each maxillary and mandibular central incisor (mesial, distal, medio-
buccal and medio-palatal/lingual), as described previously (Perinetti et
al., 2003). Briefly, this protocol consisted of recording the presence of
supragingival plaque (PL+), gingival bleeding within 15 seconds after
probing (BOP+) and probing depth (PD). The GCF collection was per-
formed on two sites on each maxillary and mandibular central incisor, at
the mesial and distal aspects using #25 standardized sterile paper strips
(Inline; Torino, Italy) inserted 1 mm into the gingival crevice and left in
situ for 60 seconds (Perinetti et al., 2003). The four samples from the
same dental arch, either maxillary or mandibular, were pooled.
Alkaline Phosphatase (ALP) Activity
The ALP activities were determined spectrophotometrically, as
described previously (Perinetti et al., 2008) and the results expressed as
total activity in muſsample.
Statistical Analysis
The significance of the differences in enzyme activities among
the CVM phases (irrespective of the dentition phase) and among the den-
tition phases (per each dental arch, irrespective of the CVM phase) was
assessed through non-parametric tests (Kruskal-Wallis and Mann-
Whitney). The significance of the correlation of the GCF ALP activity
with chronological age in the whole sample also was assessed by a
Spearman rho value, a measure of the linear correlation between two variables.
In addition, the subjects were clustered into three groups accord-
ing to their growth phases, as pre-pubertal (CS1 and CS2), pubertal (CS3
and CS4) and post-pubertal (CS5 and CS6). This clustering was used for
the calculation of the effects size (ES) coefficients (Cohen, 1992). The
ES coefficient is the ratio of the difference between the recordings of two
different groups, i.e., GCF ALP activity of the pre-pubertal and pubertal
groups, divided by the within-subject standard deviation (SD). The ES
coefficient also has been used as an index of potential diagnostic accu-
racy of GCF ALP activity (see below).
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Perinetti et al.
MAIN RESULTS AND INTERPRETATION
Clinical Conditions
The median values (as well as the 25" and 75th percentile val-
ues) of the pooled maxillary and mandibular 9%PL+ (presence of supra-
gingival plaque) and %BOP+ (percent of bleeding on probing) were
12.5% (0%; 25.0%) and 6.3% (0%; 12.5%), respectively. The mean +
SD of the pooled maxillary and mandibular PD was 1.6 + 0.3 mm, dem-
onstrating optimal periodontal health. As the GCF ALP activity increases
during periodontal inflammation (Chapple et al., 1996; Perinetti et al.,
2008), periodontal health is necessary to exclude any possible unwanted
sources of this enzyme. Here, all of the subjects received a session of
professional oral hygiene and showed optimal periodontal conditions,
with low %PL+ and %BOP+ Scores and with mean PD below 2 mm.
GCF, ALP Activity and Skeletal Maturation
Due to the non-significant differences in the GCF ALP activities
between the maxillary and mandibular dental arches and gender (not pre-
Sented here), the data were pooled and are shown in Figure 5 according
to the CVM stages. The differences among the CVM stages was signifi-
cant (p < 0.01), with the activities recorded at CS3 and CS4 significantly
greater compared to those of CS2; those recorded at CS4 also were
greater significantly to both those of CS1 (p < 0.05).
Once local tissue inflammation is excluded and by considering
the GCF formation modalities (Griffiths, 2003), two sources might be
responsible for these variations in GCF ALP activity: serum ALP (as a
Systemic factor) and maxillary/mandibular growth (as a local skeletal
factor). In more detail, the serum ALP activity, which is the most used
biochemical marker for bone turnover, has been reported to increase at
puberty and to decrease in adulthood (Szulc et al., 2000).
In this regard, the similar behaviors of the GCF ALP activities of
the maxillary and mandibular sites indicates that the differential rates and
timing of the local basal bones have little influence on the GCF enzy-
matic activities, which thus would be more responsive to systemic fac-
tors. As growth areas of the maxillary and mandibular bones are not lo-
cated in close proximity to the collection sites, this observation might
explain these data. As a consequence, the type of Sagittal skeletal maloc-
clusion per se, i.e., the type of skeletal classification, is not expected to
influence the GCF ALP activity. Influence from the serum ALP can be hy-
211
Gingival Crevicular Fluid
120 – - -
º | *
Tº. | |
E 100 - | |
º I I
º I I
m) -
# * I I
= 60 -
P. I I
º |
º 40 –
D. I I
== | |
... 20 - |
3 o Pre-puberal Puberal Postpuberta
i I I. T i i
CS1 CS2 CS3 CS4 CS5 CS6
CVM stages
Figure 5. Pooled maxillary and mandibular GCF ALP activities according to
CVM stage. Data are presented as means + standard error of the mean (n = 72).
Statistically significant differences: * = with CS2; † = with CS 1 (p<0.05).
pothesized as more important, even though no previous studies have cor-
related serum ALP activities with CVM stages specifically.
Also of interest is the difference between CS1 and CS2 in terms
of enzymatic activities that, although minimal and not significant, would
be consistent with previous evidence relating to a minimal pre-pubertal
growth phase that precedes the growth spurt (Petrovic et al., 1990). The
GCF ALP activities in the post-pubertal stages (CS5 and CS6) then de-
creased to levels comparable to those of the pre-pubertal stages (CS1 and
CS2). This decrease can be explained by a reduction in serum bone ALP
activity (Szulc et al., 2000) during the post-pubertal periods. Therefore.
these data confirm the concept that systemic growth has an impact on
GCF composition.
Dentition Phase and Chronological Age as Indices of Skeletal Maturity
as Recorded Through GCF and ALP Activity
Today, there remains a lack of evidence concerning any relation-
ships between dentition phase or chronological age and GCF ALP activ-
ity. However, this information would be useful to define further the roles
of these clinical parameters for the assessment of individual skeletal ma-


212
Perinetti et al.
turity in growing orthodontic patients, and eventually to establish any
clinical implications for treatment planning.
These GCF ALP activities generally were similar, with median
values from 42.0 mL/sample (mandibular sites, late mixed dentition) to
67.5 mL/sample (maxillary sites, permanent dentition; Table 3). For both
the maxillary and mandibular sites, no significant differences were seen
for GCF ALP activity among the dentition phases, in spite of a slight in-
crease in GCF ALP activity in the early permanent dentition. Moreover,
for 65 subjects showing the same maxillary and mandibular dentition
phases, no significant differences were seen in GCF ALP activity be-
tween the two dental arches within each dentition phase (not shown).
The GCF ALP activity also showed notably large ranges in each
of the data sets. The present data are consistent with previous evidence
reporting tooth eruption as a process with intrinsic variability in terms of
the timing when compared to skeletal maturation (Nanda, 1960; Björk
and Helm, 1967; Franchi et al., 2008). Accordingly, dental maturity,
other than eruption, has been shown to have little diagnostic performance
in the identification of the onset of the growth spurt (Perinetti et al.,
2011b).
The correlation of GCF ALP activity with chronological age is
shown in Figure 6. For both the maxillary and mandibular sites, no sig-
nificant correlations were seen, with Spearman’s rho values of 0.101 and
0.105, respectively (p > 0.3). In line with these data, there is previous
evidence showing that nine-year-old boys and fourteen-year-old girls
most likely are to be in their pre-pubertal and post-pubertal stages, re-
Spectively (Baccetti et al., 2006).
Table 3. GCF ALP activities (mu/sample) in the maxillary and man-
dibular sites according to their dentition phase. Data are presented as
median (as well as the 25th and 75th percentile values in parentheses);
n = 85. Diff= significance of the differences between the maxillary and
mandibular sites or among the phases of the dentition; NS = no statisti-
cally significant difference.

Dentition phase Maxillary Mandibular Diff
º 58.5 (31.4; 85.2) 43.5 (27.5-62.4) | NS
Late mixed 48.9 (26.4; 89.5) 42.0 (27.8-78.9) NS
Permanent 67.5(29.7; 108.9) 59.5 (31.5-93.8) NS
Diff NS NS
213
Gingival Crevicular Fluid
# 250 - = Maxillary
E = ~ A Mandibular
5, 200- A ºn tº
S A
E 150 -
*
= 100 -
§
º:
< 50 -
L-
Q
0 0 I
7 8 9 10 11 12 13 14 15 16 17 18
Age (years)
Figure 6. GCF ALP activities of the collection sites according to chronological
ages. GCF ALP activities of the maxillary (red squares) and mandibular (green
triangles) sites (n = 85). Spearman rho values: maxillary sites, 0.101; mandibular
sites, 0.105 (p → 0.3).
As mentioned above, however, chronological age shows wide
Variations when correlated with maturation phases during adolescence.
with a consequent low diagnostic performance for the detection of the
onset of the pubertal growth spurt (Baccetti et al., 2006). These consid:
erations, thus, would be consistent with little biological correlation be:
tween chronological age and individual skeletal maturation, at least in
the circumpubertal age range. Finally, although the use of dentition phase
and chronological age to define individual timing and responsiveness to
treatment is still widespread in both clinical practice and research, they
should not be used for this purpose.
Diagnostic Potential of GCF and ALP Activity in Detecting the Pubertal
Growth Spurt
The maxillary and mandibular pooled GCF ALP activities clus-
tered according to the growth phases (pre-pubertal, pubertal and post-
pubertal) are shown in Figure 7. Statistically significant differences be:
tween the groups were seen for all of the comparisons (p = 0.001). The
ES coefficients (see discussion below) between the pubertal group with

214

Perinetti et al.
140 -
º
C. -
5 120 ES, 1.80 ES, 1.03
# 100 - I I | I l
* 80 -
P
= 60 -
º
º -
a 40 -
—l
† 20 - -
3 0 Pre-pubertal Pubertal Post-pubertal
CS1-CS2 CS3-CS4 CS5-CS6
CVM stages
Figure 7. Pooled maxillary and mandibular GCF ALP activities accord-
ing to growth phases and the corresponding effects size coefficients.
Data are presented as means E standard deviation. ES = effects size co-
efficients, as indicated. CS1-CS2 n = 26, CS3–CS4 n = 23, CS5-CS6 n
= 23.
-
respect to the pre-pubertal and post-pubertal groups were 1.80 and 1.03,
respectively.
The clinical usefulness of a biomarker for the identification of
the pubertal growth spurt is dependent critically upon the accuracy that
Such a diagnostic tool has. Therefore, a critical approach to assess the
relevance of GCF ALP activity as a diagnostic aid in orthodontics has to
rely on the concept that to have high accuracy, the measurement out-
comes recorded in two groups of subjects (i.e., pubertal vs. pre-pubertal
or post-pubertal) have to show large enough differences between the
groups, as compared to their corresponding inter-subjects variations.
A statistical approach to quantify this ratio is provided by the
calculation of the ES coefficient (Cohen, 1992). In particular, a diagnos-
tic tool may be considered as accurate when the corresponding ES coef-
ficient at least equal to 1.0 (Perinetti and Contardo, 2009). The present
data, thus, provide evidence to support the use of GCF ALP activities as
a reliable biomarker, especially in the diagnosis of the onset of the puber-
tal growth spurt, which has major clinical implications (Petrovic et al.,
1990).
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Gingival Crevicular Fluid
CONCLUSIONS AND CLINICAL IMPLICATIONS
The diagnostic use of GCF in orthodontics was proposed some
time ago (Last et al., 1988), with the aim of monitoring tissue responses
to tooth movement. For instance, markers of bone resorption (Insoft et
al., 1996), bone deposition (Perinetti et al., 2002), inflammation (Ue-
matsu et al., 1996) and necrosis (Perinetti et al., 2003, 2005) have been
reported to be sensitive to tooth movement. However, none of these pre-
vious investigations have focused on the relationships between growth
and GCF composition.
Recent evidence has shown that the pubertal growth spurt can be
detected at the level of the GCF and, therefore, the GCF ALP activity
appeared to be a valid candidate as a non-invasive biomarker of the pu-
bertal growth spurt in periodontally healthy subjects scheduled for ortho-
dontic treatment. Moreover, given the temporal overlap of the mandibu-
lar growth spurt during the pubertal growth phase (CS3 and CS4; Franchi
et al., 2000), the GCF ALP activity can be proposed as a biomarker of
the onset of the mandibular growth spurt, which will have relevant diag-
nostic purposes in orthopedic treatment of Class II subjects.
GCF analysis also would offer several advantages from a clinical
standpoint: its collection involves a simple, rapid and non-invasive pro-
cedure that can be performed in a clinical setting, even in the case of
multiple GCF collections. Moreover, ALP activity can be determined
through routine and cheap laboratory analyses that already are available.
ACKNOWLEDGEMENTS
The authors are grateful to Drs. Marta Berton, Giulia Marcon,
Luisa Marsi and Bruno Di Leonardo (University of Trieste, Trieste, Italy)
for their clinical assistance, and to Dr. Christopher Paul Berrie (Telethon
Institute for Genetics and Medicine, Naples, Italy) for his critical reading
of the manuscript.
REFERENCES
Alfano MC, Brownstein CN, Chasens AI, Kaslick RS. Passively gener-
ated increase in gingival crevicular fluid flow from human gingiva. J
Dent Res 1976:55:1132.
Baccetti T, Franchi L, Cameron CG, McNamara JA Jr. Treatment timing
for rapid maxillary expansion. Angle Orthod 2001;71:343-350.
216
Perinetti et al.
Baccetti T, Franchi L, De Toffol L., Ghiozzi B, Cozza P. The diagnostic
performance of chronologic age in the assessment of skeletal matur-
ity. Prog Orthod 2006;7: 176-188.
Baccetti T, Franchi L. McNamara JA Jr. The cervical vertebral matura-
tion (CVM) method for the assessment of optimal treatment timing in
dentofacial orthopedics. Semin Orthod 2005; 11:119-129.
Bang JS, Cimasoni G. Total protein in human crevicular fluid. J Dent
Res 1971:50: 1683.
Björk A, Helm S. Prediction of the age of maximum pubertal growth in
body height. Angle Orthod 1967:37: 134-143.
Black GV. The fibers and glands of the peridental membrane. Dent
Cosmos 1899:41: 101-122.
Brill N. Influence of capillary permeability on flow of tissue fluid into
gingival pockets. Acta Odontol Scand 1959a; 17:23–33.
Brill N. Removal of particles and bacteria from gingival pockets by tis-
Sue fluid. Acta Odontol Scand 1959b; 17:431–440.
Brill N. The gingival pocket fluid: Studies of its occurrence, composition
and effects. Acta Odontol Scand 1962:20:1-115.
Brill N, Bjom H. Passage of fluid into human gingival pockets. Acta
Odontol Scand 1959; 17:11-21.
Chapple IL, Cross IA, Glenwright HD, Matthews JB. Calibration and re-
liability of the Periotron 6000 for individual gingival crevicular fluid
samples. J Periodontal Res 1995:30:73-79.
Chapple IL, Garner I, Saxby MS, Moscrop H, Matthews JB. Prediction
and diagnosis of attachment loss by enhanced chemiluminescent as-
say of crevicular fluid alkaline phosphatase levels. J Clin Periodontol
1999:26:190-198.
Chapple IL, Socransky SS, Dibart S, Glenwright HD, Matthews JB.
Chemiluminescent assay of alkaline phosphatase in human gingival
crevicular fluid: Investigations with an experimental gingivitis model
and studies on the source of the enzyme within crevicular fluid. J Clin
Periodontol 1996:23:587-594.
Ciantar M, Caruana DJ. Periotron 8000: Calibration characteristics and
reliability. J Periodontal Res 1998:33:259-264.
Cohen J. A power primer. Psychol Bull 1992; 112:155-159.
Cozza P, Baccetti T, Franchi L, De Toffol L, McNamara JA Jr. Man-
dibular changes produced by functional appliances in Class II maloc-
217
Gingival Crevicular Fluid
clusion: A systematic review. Am J Orthod Dentofacial Orthop 2006;
129:599.e1-e12.
Curtis MA, Griffiths GS, Price SJ, Coulthurst SK, Johnson NW. The to-
tal protein concentration of gingival crevicular fluid: Variation with
sampling time and gingival inflammation. J Clin Periodontol 1988; 15:
628–632.
Delima AJ, Van Dyke TE. Origin and function of the cellular compo-
nents in gingival crevice fluid. Periodontol 2000 2003:31:55-76.
Demirjian A, Buschang PH, Tanguay R, Patterson DK. Interrelationships
among measures of somatic, skeletal, dental and sexual maturity. Am
J Orthod 1985;88:433–438.
Drummond S, Canavarro C, Perinetti G, Teles R., Capelli J Jr. The moni-
toring of gingival crevicular fluid volume during orthodontic treat-
ment: A longitudinal randomized split-mouth study. Eur J Orthod
2011 Jan 27 [Epub ahead of print].
Fishman LS. Chronological versus skeletal age: An evaluation of cranio-
facial growth. Angle Orthod 1979:49:181-189.
Franchi L, Baccetti T, De Toffol L, Polimeni A, Cozza P. Phases of the
dentition for the assessment of skeletal maturity: A diagnostic per-
formance study. Am J Orthod Dentofacial Orthop 2008; 133:395-400.
Franchi L, Baccetti T, McNamara JA Jr. Mandibular growth as related to
cervical vertebral maturation and body height. Am J Orthod Dentofa-
cial Orthop 2000;118:335-340.
Franchi L, Baccetti T, McNamara JA Jr. Postpubertal assessment of
treatment timing for maxillary expansion and protraction therapy fol-
lowed by fixed appliances. Am J Orthod Dentofacial Orthop 2004;
126:555–568.
Greulich WW, Pyle SI. Radiographic Atlas of Skeletal Development of
the Hand and Wrist. Stanford, CA: Stanford University Press 1959.
Griffiths GS. Formation, collection and significance of gingival crevice
fluid. Periodontol 2000 2003:31:32–42.
Griffiths GS, Sterne JA, Wilton JM, Eaton KA, Johnson NW. Associa-
tions between volume and flow rate of gingival crevicular fluid and
clinical assessments of gingival inflammation in a population of Brit-
ish male adolescents. J Clin Periodontol 1992; 19:464–470.
Hägg U, Pancherz H. Dentofacial orthopaedics in relation to chronologi-
cal age, growth period and skeletal development: An analysis of 72 male
218
Perinetti et al.
patients with Class II division 1 malocclusion treated with the Herbst
appliance. Eur J Orthod 1988; 10:169-176.
Insoft M, King GJ, Keeling SD. The measurement of acid and alkaline
phosphatase in gingival crevicular fluid during orthodontic tooth
movement. Am J Orthod Dentofacial Orthop 1996; 109:287–296.
Ishikawa I, Cimasoni G. Alkaline phosphatase in human gingival fluid
and its relation to periodontitis. Arch Oral Biol 1970; 15: 1401-1404.
Kavadia-Tsatala S. Kaklamanos EG, Tsalikis L. Effects of orthodontic
treatment on gingival crevicular fluid flow rate and composition:
Clinical implications and applications. Int J Adult Orthod Orthognath
Surg 2002; 17:191-205. p
Lamster IB, Mandella RD, Gordon JM. Lactate dehydrogenase activity
in gingival crevicular fluid collected with filter paper strips: Analysis
in subjects with non-inflamed and mildly inflamed gingiva. J Clin Pe-
riodontol 1985; 12:153-161.
Lamster IB, Oshrain RL, Fiorello LA, Celenti RS, Gordon JM. A com-
parison of 4 methods of data presentation for lysosomal enzyme ac-
tivity in gingival crevicular fluid. J Clin Periodontol 1988; 15:347-
352. ~.
Last KS, Donkin C, Embery G. Glycosaminoglycans in human gingival
crevicular fluid during orthodontic movement. Arch Oral Biol 1988;
33:907–912.
Lee KJ, Park YC, Yu HS, Choi SH, Yoo YJ. Effects of continuous and
interrupted orthodontic force on interleukin-1beta and prostaglandin
E2 production in gingival crevicular fluid. Am J Orthod Dentofacial
Orthop 2004;125:168-177.
Loe H, Holm-Pedersen P. Absence and presence of fluid from normal
and inflamed gingivae. Periodontics 1965;149: 171-177.
Masoud M, Masoud I, Kent RL Jr, Gowharji N, Cohen LE. Assessing
skeletal maturity by using blood spot insulin-like growth factor I
(IGF-I) testing. Am J Orthod Dentofacial Orthop 2008;134:209-216.
Medlicott NJ, Tucker IG, Rathbone MJ, Holborow DW. Determination
of small sample volumes in the analysis of drugs at specific sites in
the oral cavity. J Periodontal Res 1995:30:144-146.
Nanda RS. Eruption of human teeth. Am J Orthod 1960:46:363-378.
Pashley DH. A mechanistic analysis of gingival fluid production. J
Periodontal Res 1976; 11:121–134.
219
Gingival Crevicular Fluid
Perinetti G, Baccetti T, Contardo L., Di Lenarda R. Gingival crevicular
fluid alkaline phosphatase activity as a non-invasive biomarker of
skeletal maturation. Orthod Craniofac Res 2011a; 14:44-50.
Perinetti G, Contardo L. Posturography as a diagnostic aid in dentistry: A
systematic review. J Oral Rehabil 2009:36:922–936.
Perinetti G, Contardo L, Gabrieli P. Baccetti T, Di Lenarda R. Diagnostic
performance of dental maturity for identification of skeletal matura-
tion phase. Eur J Orthod 2011b Feb 23 [Epub ahead of print].
Perinetti G, Paolantonio M. D'Attilio M. D'Archivio D, Dolci M. Fem-
minella B, Festa F, Spoto G. Aspartate aminotransferase activity in
gingival crevicular fluid during orthodontic treatment: A controlled
short-term longitudinal study. J Periodontol 2003;74: 145-152.
Perinetti G, Paolantonio M, D'Attilio M, D'Archivio D, Tripodi D, Fem-
minella B, Festa F, Spoto G. Alkaline phosphatase activity in gingival
crevicular fluid during human orthodontic tooth movement. Am J Or-
thod Dentofacial Orthop 2002; 122:548–556.
Perinetti G, Paolantonio M, Femminella B, Serra E, Spoto G. Gingival
crevicular fluid alkaline phosphatase activity reflects periodontal
healing/recurrent inflammation phases in chronic periodontitis pa-
tients. J Periodontol 2008;79:1200-1207.
Perinetti G, Serra E, Paolantonio M, Brue C, Meo SD, Filippi MR, Festa
F, Spoto G. Lactate dehydrogenase activity in human gingival crevi-
cular fluid during orthodontic treatment: A controlled, short-term lon-
gitudinal study. J Periodontol 2005;76:411–417.
Persson GR, DeRouen TA, Page RC. Relationship between gingival
crevicular fluid levels of aspartate aminotransferase and active tissue
destruction in treated chronic periodontitis patients. J Periodontal Res
1990:25:81-87.
Persson GR, Page RC. Effect of sampling time and repetition on gingival
crevicularfluid and aspartate aminotransferase activity. J Periodontal
Res 1990:25:236-242.
Petrovic A, Stutzmann J, Lavergne J. Mechanism of craniofacial growth
and modus operandi of functional appliances: A cell-level and cyber-
netic approach to orthodontic decision making. In: Carlson DS, ed.
Craniofacial Growth Theory and Orthodontic Treatment. Monograph
23, Center for Human Growth and Development, The University of
Michigan, Ann Arbor 1990;13-74.
220
Perinetti et al.
Samuels RH, Pender N, Last KS. The effects of Orthodontic tooth
movement on the glycosaminoglycan components of gingival crevi-
cular fluid. J Clin Periodontol 1993:20:371-377.
Skapski H, Lehner T. A crevicular washing method for investigating
immune components of crevicular fluid in man. J Periodontal Res
1976; 11:19-24.
Stoller NH, Karras DC, Johnson LR. Reliability of crevicular fluid
measurements taken in the presence of supragingival plaque. J Perio-
dontol 1990;61:670–673.
Sueda T, Bang J, Cimasoni G. Collection of gingival fluid for quantita-
tive analysis. J Dent Res 1969:48: 159. y
Szulc P, Seeman E. Delmas PD. Biochemical measurements of bone
turnover in children and adolescents. Osteoporos Int 2000; 11:281-
294,
Tollefsen T, Saltvedt E. Comparative analysis of gingival fluid and
plasma by crossed immunoelectrophoresis. J Periodontal Res 1980;
15:96-106.
Uematsu S, Mogi M, Deguchi T. Interleukin (IL)-1 beta, IL-6, tumor ne-
crosis factor-alpha, epidermal growth factor and beta 2-microglobulin
levels are elevated in gingival crevicular fluid during human ortho-
dontic tooth movement. J Dent Res 1996:75:562–567.
Uitto VJ. Gingival crevice fluid: An introduction. Periodontol 2000
2003:31:9-11.
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222
ORAL FLUID-BASED DIAGNOSTICS AND
APPLICATIONS IN ORTHODONTICS
Wellington J. Rody Jr., Laura R. Iwasaki, Oleg Krokhin
ABSTRACT
Abilities to predict and monitor accurately onset, progression and treatment out-
comes of human conditions and diseases through non-invasive means are desir-
able goals in health care promotion and delivery. The application of proteomic
techniques and strategies to the field of medicine is known as clinical pro-
teomics which, in turn, is devoted largely to one main idea: biomarker discovery
in body fluids. Although proteins are fragile molecules that need sophisticated
techniques to be characterized, proteomic platforms developed over the past few
years have given clinicians the ability to identify protein biomarkers in various
human clinical samples, including saliva and gingival crevicular fluid (GCF).
Therefore, the main goal of this chapter is to provide background knowledge so
the reader can understand potential applications of oral fluid-based diagnostics
in the field of orthodontics and dentofacial orthopedics.
KEY WORDS: proteomics, gingival crevicular fluid (GCF), saliva, orthodontics,
biomarkers
INTRODUCTION
Abilities to predict and monitor onset, progression and treatment
outcomes of human conditions and diseases through non-invasive means
accurately are desirable goals in health care promotion and delivery. Af-
ter the accomplishment of the human genome project, a plethora of in-
formation about genes related to various diseases has been reported
(McDermott et al., 2011). Of course, this information can provide better
clues for the development of diagnostic tools, forms of treatment and
prognosis for diseases. However, the DNA does not sustain biological
functions directly and it is recognized that not everyone with the same
genotype looks, acts or reacts the same. Indeed, phenotypes result from
the expression of an organism's genes as well as the influence of envi-
ronmental factors and the interactions between the two. These interac-
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Fluid-based Diagnostics
tions are complex phenomena that involve dynamic processes on the pro-
tein level. In order to describe the changes in all proteins expressed by a
genome, the term proteomics was invented in 1997 (James, 1997; Dom-
inguez et al., 2007) to describe the large-scale study of proteins, particu-
larly their structures and functions.
Proteins are fragile molecules that need sophisticated techniques
to be characterized. All proteins are constructed from the same set of
twenty amino acids, which are designated by either a three-letter abbre-
viation or a one-letter symbol (Table 1). The sequence of amino acids is
determined by the genetic code. This sequence and the three-dimensional
(3D) conformation of the protein are important to its specific biological
functions. The entire complement of proteins produced by an organism
or any level of its components (organs, tissues, cells) is known as the
proteome, which can vary with time and specific conditions. Hence, the
study of proteomes (i.e., proteomics) uses an “arsenal of methodologies
to capture the structural diversity of proteins and correlating this diver-
sity with the underlying biological processes” (Domon and Broder,
2004).
Contrasting with genomic studies, proteomic studies can monitor
the actual level of protein expression, as well as detect protein post-
translational modifications. These modifications play crucial roles in
regulation of protein functions and are not predicted based on genome
sequence alone (Stryer, 1995).
The application of proteomic techniques and strategies to the
field of medicine is known as clinical proteomics which, in turn, is de-
voted largely to one main idea: biomarker discovery in body fluids (Col-
antonio and Chan, 2005). With expanded research in this field, there will
be significant potential to develop simple, non-invasive screening tests
that could help to identify individuals at increased risk for systemic dis-
eases, as well as pathologic and undesirable conditions that affect the
oral cavity. Different types of body fluids are collected routinely for use
in screening tests (e.g., blood, urine, cerebrospinal fluid); however, if
meaningful screening tests could be developed using oral fluids, these
are advantageous with respect to ease of access and collection.
Proteomic research may be helpful to the field of orthodontics
and dentofacial orthopedics because at present, assessments are made
and treatment planned without measurement of current phenotypic condi-
tions at the biological or molecular levels. Indeed, potentially measurable
conditions that reflect biological and molecular variations, in the future, may
224
Rody et al.
Table 1. Naturally occurring amino acids.

Letter code &
Amino acid e Residue
Single Three mass (Da)
letter letter
Glycine G Gly 57.02 146
Alanine A Ala 71.037 ||
Serine S Ser 87.03203
Proline P Pro 97.05276
Valine V Val 99.0684 |
Threonine T Thr 1 0 1 04768
Cysteine C Cys 103.009 || 8 p
Leucine L Leu | 13.08406
Isoleucine I Ile | 13.08406
Asparagine N Asn | || 4.04293
Asparatic acid D Asp | 15.02694
Glutamine Q Gln 128.05858
Lysine K Lys 128.09496
Glutamic acid E Glu 129.04259
Methionine M Met 13 1.04048
Histidine H His 137.05891
Phenylalanine F Phe 147.0684 |
Arginine R Arg 156.1011 |
Tyrosine Y Tyr 163.06333
Tryptophan W Trp 186.07931
explain the frequently observed differences in the outcomes of treatment
between patients with similar malocclusions. Therefore, it would be ad-
Vantageous to monitor the biological and molecular events that unfold
during tooth movement, because important details may differ from per-
Son to person. Research in this area is needed to determine which “de-
tails” are measurable and important. In the meantime, the main goal of
this chapter is to provide background knowledge so the reader can under-
Stand potential applications of oral fluid-based diagnostics in the field of
Orthodontics and dentofacial orthopedics.
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Fluid-based Diagnostics
PROTEOME RESEARCH IN ORAL FLUIDS
(SALIVA AND GCF)
Proteomics is the large-scale study of proteins. With the signifi-
cant advances in molecular technologies, protein biomarker discovery
(clinical proteomics) has become one of the central applications of pro-
teomics (Hu et al., 2006). This term originally was created to mimic the
term genomics, which is the study of genes; however, it is much more
complicated. In genomics, it is necessary to work with four bases that are
stable and have similar physicochemical properties. In contrast, the in-
formation required in proteomics comes from twenty amino acids with
different properties. Proteins can denature easily, lose their 3D structure
and their specificity under unfavorable environmental conditions. Be-
sides, proteins can undergo post-translational modifications that add even
more complexity to the proteomic samples. For example, gender and age
seem to alter the physiologic expression of immunoregulatory proteins in
saliva (Fleissig et al., 2010).
Mechanical stresses from orthodontic appliances induce cells to
form biologically active molecules, especially proteins, responsible for
connective tissue remodeling and osteoclast activation (King et al.,
2000). Previous authors (Waddington and Embery, 2001; Kavadia-
Tsatala et al., 2002; Yamaguchi and Kasai, 2005; Ren and Vissink, 2008;
Iwasaki and Nickel, 2009) have described evidence that some of these
active molecules leak from the periodontal tissues into the gingival sul-
cus in measureable amounts. The same rationale applies to the use of
whole saliva that, to a certain extent, is composed of the same substances
as in the GCF (Burke et al., 2002; Marcaccini et al., 2010). Therefore,
many research groups have been trying to monitor the underlying tissue
modifications that take place after appliance activation in humans by fol-
lowing changes in the proteome composition of oral fluids.
Saliva and gingival crevicular fluid (GCF) are the most popular
targets for biomarker discovery in oral diseases (Fleissig et al., 2010).
Furthermore, the identification of secretory proteins in oral fluids as in-
dicators of reactions to mechanical stresses could be useful in monitoring
biological and molecular responses in patients undergoing orthodontic
treatment (Iwasaki and Nickel, 2009). Body fluids contain a large num-
ber of proteins that vary widely in concentration; thus, finding a single
disease-related protein is a challenging task. This approach requires the
separation and identification of each candidate protein individually and
may require depletion of highly abundant proteins, such as albumin and
226
Rody et al.
immunoglobulin, prior to proteome analysis because biomarkers in low
concentrations may be masked by the presence of these species (Pie-
trowska et al., 2010). Unfortunately, such requirements may be difficult
to achieve in instances of minute sample Volumes and protein amounts.
Saliva is the most abundant oral fluid and the easiest one to col-
lect (Malamud, 2011), and it can be obtained in medical and non-medical
settings. This fluid contains numerous bio-molecules, including those
typically found in serum for disease detection and monitoring, like the
biomarker CA 15-3 that is associated highly with breast cancer (Streckfus
et al., 2000; Wong, 2006a,b). Saliva from healthy humans is composed
of a mixture of salivary gland secretion, GCF, cell debris, micro-
organisms, serum/blood from subclinical wounds, nasal and bronchial
Secretions; thus, in terms of proteomic analysis, it is considered a com-
plex Sample.
This complexity is illustrated by a detailed comparative analysis
of saliva and serum proteomes, which was presented recently (Yan et al.,
2009; Loo et al., 2010) following a comprehensive study of the saliva
proteome in research supported by the National Institutes of Health
(Denny et al., 2008). Indeed, the protein population in saliva is different
compared to serum: cystatins, amylases, proline-rich proteins, histatin
and mucin were found to be major protein components compared to the
albumin and immunoglobulin found in serum. This difference means that
the analyses and correct assignments of different components of the pro-
tein population in saliva are critical to its success as a source of biomark-
CTS.
A large number of proteins previously have been shown to be
present in saliva, including the human immunodeficiency virus (HIV)
antibody (Reynolds and Muwonga, 2004). In dentistry, saliva has been
used to monitor periodontal disease (Socransky and Haffajee, 2005;
Giannobile et al., 2009; Gursoy et al., 2009; Kinney et al., 2011), assess
the risk of caries (Baughan et al., 2000) and cancer (Spielmann and
Wong, 2011). In orthodontics, saliva has been used to monitor growth
and development (Ghafari et al., 1994), bacterial levels (Wilson and
Gregory, 1995; Chang et al., 1999; Lara-Carillo et al., 2010) and metal
release from appliances (Mikulewicz and Chojnacka, 2010, 2011) during
orthodontic treatment.
Interestingly, few studies (Burke et al., 2002; Maraccini et al.,
2010) have used saliva as a sample to quantify inflammatory biomarkers
related to tooth movement. Orthodontic forces create local inflammatory
227
Fluid-based Diagnostics
reactions with increased capillary permeability; hence, the site-specific
nature of GCF is advantageous. Because GCF is closer to the activities of
interest and is less likely to be diluted, it could have even greater diag-
nostic value than saliva to monitor biological and molecular activities
important to orthodontics.
GCF is defined as a transudate of interstitial fluid and/or in-
flammatory exudates (Suzuki et al., 2008). The constituents of GCF arise
from a variety of sources, including host tissues and cells, microbial
plaque and serum-derived factors. Indeed, more than 100 regulatory pro-
teins so far have been detected in GCF (Buduneli and Kinane, 2011). As
with most of the physiological fluids, proper sample collection is critical
to avoid possible contamination and to provide effective sampling of the
target fluid.
Three major approaches to collecting GCF involve sample ex-
traction using glass microcapillary tubes (Waddington and Embery,
2001; Kereshanan et al., 2008; Bildt et al., 2009; Ngo et al., 2010), pe—
riopaper strips (Iwasaki et al., 2001; Balducci et al., 2007; Bostanci et
al., 2010) or durapore filter membrane (Giannopoulou et al., 2008). Par-
ticular attention should be paid to eliminate the collection of saliva or
blood components (Fig. 1). Proteins then are extracted by water-based
buffers compatible with the sample preparation. Due to the extremely
low volume of collected GCF, sample handling and identification of pep-
tides/proteins is a challenging task (Bostanci et al., 2010). It is estimated
that the amount of extracted protein is at the level of only a few micro-
grams following a typical GCF sampling. Taking into account the high
abundance of non-target proteins (such as albumin, keratins and immu-
noglobulin), only highly sensitive and selective methods are able to pro-
vide appropriate results.
Figure 1. Gingival crevicular fluid (GCF) collection with periopaper
(A) and durapore filter membrane (B). Notice the isolation with cotton
rolls to avoid contamination with saliva.

228
Rody et al.
The analysis of specific constituents in the GCF may provide
quantitative biochemical indicators for evaluation of the local cellular
metabolism that reflects the level of inflammation and the status of re-
sorption and replacement (turnover) of bone and root tissues before, dur-
ing and after orthodontic treatment (Huang et al., 2008; Tyrovola et al.,
2008; Iwasaki and Nickel, 2009). Indeed, it has been the goal of many
research groups to develop a specific antibody for human dentin proteins
(Mah and Prasad, 2004; Balducci et al., 2007; Kereshanan et al., 2008;
George and Evans, 2009) in order to monitor root resorption; however, to
date, this has been both costly and challenging.
Historically, costs in terms of labor and expenses have been high
because although early techniques for protein detection and quantifica-
tion via antibodies, such as enzyme-linked immunosorbent assays (ELI-
SAs), were sensitive and specific, these techniques could be applied to
only one analyte (i.e., a substance or chemical constituent that is deter-
mined in an analytical procedure) at a time. Further major challenges
arise due to protein folding and extensive post-translational modifica-
tions that result in shielding of molecules of interest by numerous phos-
phate and carbohydrate groups. These structural complexities of proteins
are the main barriers to the development of useful biochemical and im-
munological assays for the clinical setting.
Recently, the first studies using mass spectrometry (MS) to ana-
lyze GCF were published (Dommisch et al., 2009; Bostanci et al., 2010;
Ngo et al., 2010). This approach shows promise in the identification of
important analytes for periodontal tissue conditions and offers the advan-
tages of sensitivity and non-invasiveness. This approach and a range of
other detection techniques are described and evaluated in the next sec-
tion.
KEY TECHNOLOGIES FOR PROTEIN BIOMARKER
IDENTIFICATION AND QUANTIFICATION
By simplistic definition, a biomarker is considered to be any pa-
rameter that can be identified in a patient that relates to a specified out-
come. Proteomic platforms developed over the past few years have given
clinicians the ability to identify rapidly novel protein biomarkers in vari-
ous biological matrices from cell cultures (lysates, supernatants) to hu-
man clinical samples (serum, plasma, saliva and urine). Quantitative data
are important to advance biomedical research in that such data allow
more powerful statistical analyses and the capacity to discern differences.
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Fluid-based Diagnostics
Identifying and measuring the best biomarkers for orthodontics likely
will involve unique expertise and extensive effort beyond the scope of a
single individual or laboratory (Sharon et al., 2010). Thus, a team ap-
proach that brings together clinicians and basic scientists offers the best
chance for success. .
Immunoassays
An immunoassay is a biochemical test that can detect or measure
a substance in a complex solution via the binding between antigens and
antibodies and detectable labels that signal this binding. The accuracy
and reliability of an immunoassay depend on the specificity and affinity
of the particular antigen-antibody binding of interest and the detection of
the signal.
Solid-phase immunoassay is one of the most widely used immu-
nologic techniques. It currently is automated and is employed in clinical
medicine for detection of specific antigens or antibodies (e.g., the identi-
fication of thrombospondin [TSP-1]) in serum as a potential biomarker
for prostate cancer (Shafer et al., 2007). The principles of solid-phase
immunoassays are easy to understand. Basically, the capture antibody is
bound to the surface of a solid medium. After incubation with the sam-
ple, the target protein is trapped to the surface and then can be visualized
through an enzymatic reaction.
Enzyme-linked Immunosorbent Assays (ELISAs). If the test uses
anti-immunoglobulins that are labelled with an enzyme that can be de-
tected by the appearance of a color on addition of proper substrate, the
test is called enzyme-linked immunosorbent assay (ELISA). In the “indi-
rect” ELISA, each microplate well is coated with a known antigen and
the patient’s body fluid then is added (Engvall and Perlmann, 1971; Van
Weemen and Schuurs, 1971; Voller et al., 1979). Because the ELISA can
be performed to evaluate either the presence of a specific antigen or
antibody in a sample, it is a useful tool for serum diagnosis of infectious
diseases (e.g., acquired immune deficiency syndrome and West Nile vi-
rus; Torno et al., 2007).
Protein Blots. Protein blotting techniques are used in basic re-
search as well as clinical testing and involve two steps: immobilization of
proteins on membranes and detection using antibodies. One of the most
common of these techniques is Western blotting because it is simple,
reliable and cost-effective (Burnette, 1981). In the Western blot, gel
electrophoresis is employed to separate the proteins in the sample by
230
Rody et al.
isoelectric point, molecular weight or other specific characteristic; then
the separated proteins are moved onto a solid support like paper or a
membrane (Towbin et al., 1979). Thus, the support becomes a duplicate
of the electrophoretic gel, which then can be submitted to an enzymatic
reaction, similar to the ELISA, to test for the presence of specific anti-
gens or antibodies.
Depending on the specifics of the electrophoresis, Western blot-
ting can provide information about proteins of interest in the sample
fluid, in terms of molecular weight and presence of particular isoforms;
however, it is only semi-quantitative in that only relative amounts of the
proteins or components can be determined. Protein blotting methods like
the Western are technique sensitive (MacPhee, 2010) but effective when
the main aim is detection of a particular protein or form of protein (e.g.,
in the confirmation of Lyme disease; Bunikis and Barbour, 2002). For
differential clinical information about conditions associated with ortho-
dontic treatment, however, quantitative data about a number of biomark-
ers likely is needed.
Microarrays. Protein binding microarrays use miniaturization in
chip or microscope slide format, and multiplex ELISA platforms to
quantify large numbers of biomarkers in complex samples in just one
experiment. When these analyses are conducted in parallel or when
automation is employed to process many samples rapidly, these types of
multiplex assays also can be high-throughput. Thus, protein microarrays
potentially are powerful tools for diagnostics (Spisak et al., 2007;
Chaerkady and Pandey, 2008). The most common protein microarray is
the antibody microarray in which small sized droplets of antibodies are
fixed in an orderly pattern onto a glass surface and are used as capture
molecules to detect biomarkers in body fluids. When a sample of body
fluid is applied to the glass surface, given target proteins, if present, are
bound by the specific capture antibodies and trapped on the solid surface
of the chip. The antigen-antibody complexes then can be visualized and
quantified through the addition of fluorescent dyes and by using a mi-
croarray laser scanner (Joos et al., 2000; Lin et al., 2003; Prabhakar et
al., 2004). By systematically arranging multiple antibodies onto a glass
Support, detection of multiple biomarkers in one experiment is made pos-
sible. Indeed, one chip can be spotted with many wells of identical cus-
tomized antibody arrays.
In order to improve the reliability of the method, each antibody
droplet, together with the positive and negative control normally is
printed in quadruplicate (Fig. 2). Data extraction and analysis are performed
231
Fluid-based Diagnostics
Proteinſhip
Customized
Art
Figure 2. Protein chip spotted with sixteen wells of identical customized anti-
body arrays. In this experiment, the array was customized to indentify the bio-
markers interleukin-1 (IL-1), osteoprotegerin (OPG) and matrix metalloprotein-
ase-9 (MMP-9). Notice that each antibody droplet, together with the positive
(POS) and negative (NEG) control, is printed in quadruplicate.
with specific software. Previous research has demonstrated that the mi-
croarray test format provides equivalent performance to ELISA tests and
offers a significant advantage in convenience and cost when compared to
traditional test formats (Walter et al., 2002; Bacarese-Hamilton et al., 2004).
At present, immunoassays are the primary tool for the determina-
tion of macromolecular concentrations in biological samples for many
reasons, including relatively high sensitivity, high specificity and wide
applicability (Spisak et al., 2007). In addition, microarray technology
now permits wide-scale proteome analysis. Nevertheless, these methods
have limitations to their clinical application. For example, immunologi-
cal assays require the use of specific antigens or antibodies that often are
not obtained easily. In fact, not all antibodies make good capture rea-
gents as some do not bind well to intact proteins. Also, the nature of the
solution and the details of the conformation and orientation of the ele-
ments all can affect binding. Furthermore, possibility for cross-reactivity




232
Rody et al.
between antigens with antibodies that resulted from different but similar
antigens always exists.
Comprehensive analysis of the proteins in body fluids are chal-
lenged further by the high dynamic range or, in other words, exceedingly
broad range of concentrations of various proteins contained in these fluid
samples, which is estimated to exceed ten orders of magnitude (Corthals
et al., 2000). This presents problems with accurate detection and quanti-
fication in that many important biomarkers have low expression levels
(Apweiler et al., 2009). Besides, immunoassays use calibration curves in
order to quantify proteins in unknown samples. Basically, a calibration
curve is the relationship between signals produced by a given antigen (y-
axis) for a range of known concentrations of the antigen (x-axis). An
ideal calibration curve would be linear (slope = 1.0) over a range of con-
centrations broader than the range of concentrations in the samples to be
measured. In addition, all the calibration data fit this relationship per-
fectly (coefficient of determination, r = 1.0). In reality, calibration
curves often are non-linear with r < 1.0, hence, in attempt to minimize
errors in interpretation a set of calibration standards is necessary to per-
form a quantitative immunoassay (Oellerich, 1980).
Mass Spectrometry (MS). Over the past two decades, the applica-
tion of MS to biomolecular analysis has revolutionized biomedical pro-
tein research (Aebersold and Mann, 2003). This advancement can be at-
tributed primarily to the development of ionization techniques that are
compatible with biomolecules. Basically, MS analysis consists of a
molecule's ionization and measuring its mass to charge ratio (m/z). This
analysis permits determination of mass, composition and, in many cases,
primary structure of molecules, like proteins, in a sample.
Detailed compositional analysis of peptides/proteins is possible
because the masses of their building blocks (amino acids) are known
(Table 1). Therefore molecular masses (or masses of molecular frag-
ments) can be calculated and compared to the measured values. With the
advent of current techniques, both qualitative and quantitative protein
analyses of minute biological samples have potential to become routine
laboratory procedures. These MS techniques will be described in brief.
Operationally, most of the proteomics procedures can be divided
in two large categories: top-down and bottom-up studies (Fig. 3). The
former deals with the analysis of intact proteins, while the latter uses pro-
teolytic digestion to reduce the size of the analytes. The latter approach
resembles puzzle assembly: since the rules of digestion are known for
233
Fluid-based Diagnostics
Top-down proteomics Bottom-up proteomics
protein sample protein sample
fractionation/purification fractionation/purification
(gel-based/HPLC) (gel-based/HPLC)
digestion
peptide fractionation (HPLC)
Mass-spectrometry Mass-spectrometry
MS and MS/MS (proteins) MS and MS/MS (peptides)
Figure 3. Bottom-up and top-down proteomic approaches.
specific enzymes, the whole picture (protein sequence) can be assembled
from small pieces. Independent of the approach used, gel-based protein
separation techniques or high-performance liquid chromatography
(HPLC) typically are utilized for fractionation of protein/peptide mixtures
prior to the analysis. Commonly, the overall procedure of protein identifi-
cation/quantification is described as HPLC-MS analysis (Gross, 2004).
Ionization is a critical step in MS technique. Only ionized mole-
cules can be separated further in mass analyzers. Two major ionization
techniques to MS (Fig. 4) that were recognized for the Nobel Prize in
Chemistry (2002) are matrix-assisted laser desorption/ionization
(MALDI) and electrospray ionization (ESI). The MALDI technique typi-
cally involves the irradiation of a sample’s spots deposited on a conduc-
tive plate with lasers (Karas and Hillenkamp, 1988). The spots consist of
co-crystallized MALDI matrix and analytes (e.g., protein sample). A ma-
trix is used to protect the protein from being destroyed by direct laser
beam and to generate a plume that contains ionized molecules of the
sample. These molecular ions then are extracted by applying potential to
a conductive target plate and further separated in mass analyzers (Zalu-
zec et al., 1995).
Electrospray ionization (ESI) is achieved by pumping the sample
solution through a thin capillary held at high voltage. During this proc-
ess, the solvent surrounding individual droplets evaporates, creating a
plume that contains protein/peptide molecules carrying multiple positive
charges (Fenn et al., 1989; Castleberry et al., 2008). Similar to MALDI,
the charged molecules then are introduced into the mass analyzer and
separated according to m/z.
234
Rody et al.
laser beam
lens
counter electrode
grid counter
| - ions electrode
i Vacuum
capillary
liquid–- Hºt + § ." —- ions
vacuum
AVolº power High-voltage
supply C power supply
Figure 4. A. Matrix-assisted laser desorption-ionization (MALDI). B: Laser
shooting 2,5-dihydroxybenzoic acid (MALDI matrix) crystals. C. Electrospray
ionization (ESI) technique.
Development of MALDI and ESI provided significant impact on
analytical chemistry of peptides and proteins due to the “soft” character
of their ionization. Indeed, these ionization procedures allow researchers
to keep biological molecules intact, in contrast with destructive ioniza-
tion methods like fast atom bombardment (FAB) employed previously
(Morris et al., 1981). Only the charged molecules can be separated fur-
ther in mass analyzer, making these ionization techniques a critical com-
ponent in overall analysis scheme.
A major difference between ESI and MALDI is variation in
charge states of the ions: while MALDI mostly produces +1 ions (repre-
Sented as MH+), in ESI higher charge states typically are observed (+2,
+3 for peptides and even higher for intact proteins). There are many
types of mass analyzers that can be used to measure masses (m/z values):
magnetic sector analyzers, ion-traps, quadrupoles, time-of-flight (TOF),
Orbitrap and Fourier transform mass spectrometers (FTMS). The latter
three techniques provide superior mass resolution and accuracy of mass
measurement (Gross, 2004; Han et al., 2008).




235
Fluid-based Diagnostics
The mass measurement of intact proteins or peptides, referred to
as single mass spectrometry (single MS), typically cannot provide confi-
dent information as the masses of intact proteins/peptides are not unique.
Identification of purified proteins (or simple mixtures of proteins) is pos-
sible, however, following enzymatic digestion and the measuring of the
masses of several fragments. Protein identification then can be performed
based on accurate measurement of the masses for several peptides origi-
nating from the same protein.
Peptide mass fingerprinting (PMF) is a technique used to iden-
tify proteins by matching their constituent fragment masses (peptide
masses) to the theoretical peptide masses generated from a protein or
DNA database (Henzel et al., 1993; James et al., 1993). The first step in
PMF is that an intact, unknown protein is cleaved with a proteolytic en-
zyme to generate peptides. For example, trypsin (the most popular en-
zyme in proteomics) cleaves proteins at C-terminal positions of lysine
(K) and arginine (R). The premise of PMF is that every unique protein
will have a unique set of peptides and, hence, unique masses (Jensen et
al., 1997). Thus, when horse myoglobin is digested with trypsin and
masses of proteolytic fragments are measured using hybrid MALDI – Qq
(quadrupole) TOF mass spectrometer, theoretical masses of expected
tryptic fragments can be calculated and compared to observed values
(Fig. 5). Presence of multiple matching peptides yields a high confidence
of identification of the original protein that is possible only because the
sequence of horse myoglobin is known. This emphasizes that proteomic
measurements rely heavily on reliable genomic information of the organ-
isms being studied.
Modern MS instruments also can perform the isolation and
fragmentation of selected peptides. The process of fragmentation of pep-
tides/proteins and the measurement of the masses of their fragments in
mass spectrometers often is referred to as tandem MS or MS/MS (Fig. 6).
In the case of ESI MS, spectra of the same digest will contain multiply
charged peaks that represent peptides. Fragmentation of peptides typi-
cally occurs at peptide bonds; therefore, masses of adjacent fragments
differ by exact values corresponding to the masses of the 20 naturally
occurring amino acid residues. The assignment of the sequence of sev-
eral consecutive amino acids by MS/MS typically allows for the highly
confident identification of the source protein (Yates et al., 1995).
236

Rody et al.
1606.864
| 616.184
P
3 ||
Qu
E
g 748.447 1815,919
º - 1502,684 IT
º 1271,677
& - 1982,070
1885,043
1853,976 2443.254
1378.858 -
2110,169
735,500 941.482
Llullal l l, ill 1. llam Lillºu.J. … . . . M
gºo" soo"Tooo-ºooººooººoo isoo ºn 200 2200 mſ:
Figure 5. Example of peptide mass fingerprinting of horse myoglobin
by MALDI MS (tryptic digest). Peptide peaks appear as MH' ions.
Horse myoglobin amino acid sequence is known from database. Calcu-
lated m/z values for tryptic peptides are: GLSDGEWOQVLNVWGK
(1815.903), VEADIAGHGQEVLIR (1606.855), LFTGHPETLEK
(1271.664), HGTVVLTA LGGILK (1378.841) and GHHEAELK-
PLAQSHATK (1853.692). Experimentally measured m/z values
matching horse myoglobin sequence are underlined: 616.184, 735.500,
748.447, 941.482, 1271.677, 1378.858, 1502.684, 1606.864, 1815.919.
1853,976, 1885,043, 1982,070, 2110.169 and 2443.254 (MH"). The
Values that are not underlined represent non-protein contents of the
molecule.
Modern mass spectrometers allow very fast MS/MS fragmenta-
tion (up to 20 to 50 spectra per second) providing fast duty cycle. This
analysis is performed in a “data-dependent” manner; that is, the instru-
ment performs the initial MS survey scan, chooses peptides for fragmen-
tation and collects their MS/MS results. As noted before, most of the
modern high-throughput bottom-up proteomic approaches utilize highly
efficient peptide HPLC fractionation followed by high-speed MS/MS
data acquisition. HPLC allows for effective separation of peptide mix-
tures and optimal delivery of analysed molecules into a mass spectrome-
ter.
237
Fluid-based Diagnostics
MS MS/MS
GQEWLIR
QEVLIR
EVIR
peptide
¥
M/z
VLIR 814.5
measure LIR 757.5
select peptide fragmen- fragments’ m/z
tation
Figure 6. Fragmentation of peptides and identification of their amino
acid sequence trough MS/MS. Calculated m/z values for MS/MS frag-
ments; R = 175.1; IR = 288.2: LIR = 401.3; VLIR = 500.4; EVIR =
629.4; QEVLIR = 757.5; and GQEVLIR = 814.5. Notice that the dif-
ference between the m/z values of adjacent fragments gives the mass of
one of the naturally occurring amino acids (i.e., 288.2 – 175.1 = 113.1;
this residue mass may correspond to isoleucin (I) or leucine (L). There-
fore, MS/MS allows gradual sequential identification of amino acid
composition of the unknown peptide.
Continued progress in the development of MS instrumentation
over the past two decades has made proteomics one of the most dynamic
fields in the life sciences. Detection limits down to attomole (10” of a
mole) levels have been demonstrated, opening possibilities for in-depth
analysis of proteins in biological samples. Not surprisingly, this approach
has received increased attention for clinical application (Choi et al.,
2010; Mischak et al., 2010). The goal of these studies is to find biomark-
ers, peptide/protein molecules that will indicate occurrence of a particu-
lar disease or process leading to it. Once these molecules are found in the
samples under investigation, this work may lead to better diagnostics and
Outcomes of a treatment.
Many traditional diagnostic procedures have involved the inva-
sive collection of cells or tissues for further examination. However, in-
creased emphasis is being placed on non-invasive diagnostic procedures,
involving the collection and proteomic analysis of blood/serum, urine,
saliva or tears (Okrojek et al., 2009; Yan et al., 2009; Court et al., 2011;
Wang et al., 2011). There is reason to believe that the detailed analysis of
protein levels and post-translational modifications of proteins in biologi-
cal fluids will be indicative of the conditions of particular organ and the
choice of correct body fluid to analyze is crucial. For example, kidney
diseases are most likely to change the protein patterns in urine (Mischak









238
Rody et al.
et al., 2010), while cerebrospinal fluid is a better choice than blood
plasma for examining brain diseases (Choi et al., 2010).
The identification and study of biomarkers starts with defining
the target disease and the correct selection of the samples. This selection
is critical since the initial step of biomarker discovery deals with detailed
analysis of a limited number of samples at a “discovery” stage (Fig. 7).
These samples have to be representative for the patients with the particu-
lar disease (or stage of the disease) and for healthy (non-affected) indi-
viduals, since comparative analyses typically are performed.
Input from healthcare specialists who use traditional diagnostics
tools is critically important. Following the initial identification of a rela-
tively large number of potential biomarkers (up- or down-regulated in
patients’ samples), each molecule must be screened in a large number of
samples using simplified (more targeted) techniques. Then, limited num-
bers of selected molecules that show the best correlations with disease
status/progression can be tested via wide screenings for validation as
biomarkers. Finally, after the test has been accepted by clinicians and
patients, the biomarker needs to be implemented clinically through ap-
proval of the test by regulatory authorities (Alymani et al., 2010; Pirmo-
hamed, 2010).
Top-down analysis of GCF using surface-enhanced laser desorp-
tion/ionization (SELDI)-MS was reported recently (Dommisch et al.,
2009). This approach is similar to the standard MALDI application, ex-
cept for a preliminary fractionation/cleaning step occurring on the treated
surface of the SELDI chips. Following sample enrichment on surface-
bound functional groups (e.g., anion-, cation-exchange, hydrophobic)
MALDI matrix is applied, then MS using laser desorption/ionization.
This approach permits the fast screening of intact peptides/proteins
across multiple samples.
The reduced sensitivity of mass spectrometers at higher molecu-
lar weight means that only relatively small intact peptides/proteins (1-15
kDa) typically are detected by this method. Indeed, Dommisch and col-
leagues (2009) were able to find elevated levels of human neutrophilpep-
Increasing number of samples (analysis throughput)
Discovery — Validation — Clinical implementation
Decreasing number of monitored compounds (potential biomarkers)
Figure 7. Biomarkers discovery: typical workflow.
239
Fluid-based Diagnostics
tides (NPHs) and human cathelicidin LL-37 in inflamed periodontal sites
compared to healthy ones. These antimicrobial peptides are secreted by
neutrophils and play important role in the innate immune response. In
addition to the reduced sensitivity for high mass measurements, another
disadvantage of classical SELDI-MS is the inability to confirm protein
identification by MS/MS because the sequence identification of the ob-
served peaks requires prior information on the molecular properties of
possible components or confirmation via an independent method (Schaub
et al., 2005).
The full arsenal of currently available proteomic methods was
employed by Ngo and coworkers (2010) to assess the composition of
GCF using both bottom-up and top-down approaches. This combination
of methods identified 33 peptides and 66 proteins in GCF. The low mo-
lecular weight peptides were found to be originating from various pro-
teins (e.g., proline-rich phosphoprotein, albumin, beta-globin, statherin).
These are products of protein cleavage with specific proteases, which by
themselves represent a specific class of compounds often considered as
biomarkers. Their activities in diseased individuals are responsible for
the appearance of smaller peptides as products of the cleavage of more
abundant proteins. Profilin, cofilin and gelsolin were among recently
identified proteins in GCF reported by these authors and also by our
group (data not published), who used bottom-up HPLC-MS analysis of
GCF.
The recent HPLC-MS analysis of 40 GCF samples from 10 sub-
jects (five healthy and five with aggressive periodontitis) showed in-
creased levels of bacterial, viral and yeast proteins in the disease patients
(Bostanci et al., 2010). Contrary to a previously described report (Dom-
misch et al., 2009), they also found the presence of defense-related pro-
teins, such as Cystatin-B and defensins only seen in healthy individuals.
In total 154 protein were identified; surprisingly, pro-inflammatory cyto-
kines or periodontal pathogen proteins rarely were detected. These unex-
pected results should be addressed in future studies involving analysis of
GCF.
CLINICAL APPLICATIONS IN ORTHODONTICS
To get relevant answers, a first step is to ask relevant questions.
Therefore, protocols and techniques must be designed around clinical
questions. In general, biomarkers can be used for diagnostic and prog-
nostic purposes. Determining the presence of active periodontal disease
240
Rody et al.
or root resorption during orthodontic treatment is an important potential
diagnostic application. On the other hand, forecasting conditions for
faster or slower tooth movement or pain due to relatively high or low
loads of certain proteins in the periodontium represent potential prognos-
tic applications.
Candidate proteins and their clinical relevance to orthodontics
have been identified (Table 2); however, it is important to emphasize that
more research in this area is needed to determine a ranking of the most
relevant for meaningful diagnostic and prognostic information. Readers
are referred to current reviews (Ren and Vissink, 2008; Iwasaki and Nick-
Table 2. Biomarkers found in human GCF and their respective clinical relevance
to orthodontics.

BIOMARKER CLINICAL
CATEGORY NAME RELEVANCE REFERENCES
* Monitor bone
º dur- Kawasaki et al., 2006
e RANKL g Nishijima et al., 2006
Osteoclastogenesis movement
OPG e Toygar et al., 2008
related factors * Monitor root Tyrovola et al., 2008
resorption dur- George and Evans, 2009
ing tooth
movement
Pr0: TNF * Reveal the rate Uematsu et al., 1996
Infl to ſ". 2, 6 s of tooth move- Deschner et al., 2000
nilammatory -** *, *. nent Iwasaki et al., 2001, 2005, 2009
cytokines Anti: IL-1Ra, >k
IL-4, 10 and 13 Control bone e Ren et al., 2007
5 remodeling Giannopoulou et al., 2008
* Reveal the adap- Apajalahti et al., 2003
Extracellular MMPS tation of the Ingman et al., 2005
matrix degradation TIMPS periodontal Cantarella et al., 2006
factors ligament to me- Bildt et al., 2009
chanical forces Capelli et al., 2011
* Monitor root
Dentin breakdown DSP resorption dur- ºº:
products DPP ing tooth Kereshanan et al 2008
movement • y
241
Fluid-based Diagnostics
el, 2009) for comprehensive lists of biomarkers of paradental tissue turn-
over found in the GCF during orthodontic treatment.
Clinical proteomics is an emerging field in medicine but it is
progressing at a relatively slow pace in dentistry. That being said, it is
time to bring researchers and clinicians together in order to brainstorm
about how to move forward to improve the field. Potential clinical appli-
cations to be kept in mind are enumerated below.
Monitor Tissue Changes During Orthodontic Tooth Movement
Orthodontic treatment still consists of numerous appliance sys-
tems that usually are chosen without full appreciation for biological is-
sues. Included among the important biological events associated with
orthodontic therapies are the inflammatory responses that initiate tissue
changes and consequent bone and periodontal ligament (PDL) modeling
and remodeling (Hatch, 2011). •
One of the most important breakthroughs in bone biology has
been the identification of the role of inflammatory mediators, like cyto-
kines, in bone change and homeostasis. Increased concentrations of cy-
tokines in human GCF during orthodontic tooth movement have been
demonstrated by several studies (Uematsu et al., 1996; Iwasaki et al.,
2005; Ren et al., 2007; Giannopoulou et al., 2008). Cytokines are classi-
fied as pro-inflammatory and anti-inflammatory. Pro-inflammatory ones
are tumor necrosis factor (TNF), interleukin-1 (IL-1), IL-2, IL-6 and IL-
8. Anti-inflammatory cytokines are interleukin-1 receptor antagonist (IL-
1RA), IL-4, IL-10 and IL-13.
Cytokines act synergistically or antagonistically on each other.
The relative activities of inflammatory mediators may reveal the rate of
tooth movement. Once the microenvironment of periodontal tissue is
activated by an orthodontic force, key pro-inflammatory cytokines are
produced to trigger a cascade of cellular events. For example, ex vivo
experiments (i.e., in or on tissue in an artificial environment outside the
organism with the minimum alteration of natural conditions) have shown
that when human PDL cells are incubated with the pro-inflammatory
cytokine IL-13, they release significantly more IL-6, another pro-
inflammatory cytokine and significantly less IL-10, an inflammation in-
hibitor, compared to control PDL cells not exposed to IL-1B (Deschner et
al., 2000). Interleukins particularly can be important for consequent or-
thodontic tooth movement in that these cytokines not only regulate im-
mune responses in sites of inflammation, but also have autocrine/
242
Rody et al.
paracrine activities that stimulate osteoclast formation and bone resorb-
ing activities of preformed osteoclasts (Ren et al., 2007).
Higher ratios of IL-13 versus its naturally occurring competitive
antagonist, IL-1RA, in GCF from experimental sites versus control sites
have been correlated to faster tooth translation in humans (Iwasaki et al.,
2006; Iwasaki and Nickel, 2009). Hence, there already is some evidence
that clinical tests of the balance of pro- and anti-inflammatory mediators
may be useful to predict rates of orthodontic tooth movement. The previ-
ous work demonstrates the value of a ratio of complementary biomarkers
over the measurement of a single mediator to reflect the biological condi-
tions. Now, with the advancement of new proteomic technologies, re-
search to investigate broader ranges and combinations of candidate bio-
markers also should be able to advance.
Besides monitoring biomarkers of inflammation, biomarkers of
bone changes following appliance activation also could be monitored.
Osteoclast differentiation requires the binding of receptor activator of
nuclear factor kappa B ligand (RANKL), a cell membrane protein found
on osteoblast and pre-osteoblast cells, to receptor activator of nuclear
factor kappa (RANK), also a cell membrane protein but found on osteo-
clast and osteoclast-precursor cells. On the other hand, osteoprotegerin
(OPG) acts as a decoy receptor that binds to RANKL and prevents the
RANKL-RANK association, hence, blocking osteoclastogenesis. There-
fore, the balance between RANKL and OPG is of major importance in
bone homeostasis.
Abnormalities of the RANKL-to-OPG ratio have been impli-
cated in the pathogenesis of many bone diseases, including periodontitis
(Mogi et al., 2004; Chen et al., 2008). The RANK-RANKL-OPG system
also plays an important role in osteoclast differentiation during orthodon-
tic tooth movement, where the levels of RANKL in GCF have been ob-
served to increase during tooth movement, while the levels of OPG de-
creased. This is a strong indication that changes in the RANKL-to-OPG
ratio may be involved in bone modeling as a response to orthodontic
forces (Nishijima et al., 2006).
Finally, it is important to emphasize that tooth movement also
demands extensive tissue changes within the PDL. Indeed, a recent study
in rats suggested that the PDL plays a dominant role in the tissue model-
ing processes after appliance activation (Kawarizadeh et al., 2005). Ma-
trix metalloproteinases (MMPs) and their specific inhibitors, tissue in-
hibitors of metalloproteinases (TIMPs), act in a coordinated fashion to
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Fluid-based Diagnostics
regulate the turnover of periodontal tissues. Takahashi and associates
(2003) observed an increased expression of MMP-2, MMP-8, MMP-9,
MMP-13 and TIMPs genes in the PDL of rats following appliance acti-
vation (Takahashi et al., 2006). This finding, confirmed by several hu-
man studies (Apajalahti et al., 2003; Ingman et al., 2005; Cantarella et
al., 2006; Bildt et al., 2009; Capelli Jr et al., 2011), indicates that MMPs
are important biomarkers to reveal the adaptation of the PDL to me-
chanical forces.
Diagnose and Prevent Root Resorption
Root resorption is a universal term that describes the breakdown
of cementum, a tissue that forms a protective barrier around the root, and
subsequent loss of the root structure, which is formed mainly by dentin
(Owman-Moll et al., 1995). It is a complex inflammatory process and
involves various components, including mechanical forces, tooth roots,
bone cells, surrounding matrix, biologic factors and genetics. External
root resorption occurs as a result of differentiation of osteoclasts in sur-
rounding tissue that, if in close proximity to the root surface, will resorb
the root surface cementum as well as the underlying root dentin (King et
al., 2000; Rody et al., 2001). It can be caused by many factors including
trauma, periapical infectious lesions, periodontal diseases and orthodon-
tic treatment.
The accurate diagnosis and prevention of root resorption is an
important health goal. Although clinical characteristics such as root
shape and age are well-established risk factors for root resorption, such
features are not enough to identify individuals at risk (Brezniak and
Wasserstein, 1993a,b; Mirabella and Artun, 1995). Unfortunately, the
only clinical method currently available to detect root resorption is ra-
diographs. Problems of technique, standardization, limited points of view
and radiation exposure remain significant problems of radiographs. This
method also has many pitfalls including the fact that radiographs do not
indicate if the process of root resorption is active or inactive.
Owman–Moll and colleagues’ study (1995) in humans showed
that histological methods were able to detect root resorption after seven
weeks of orthodontic treatment; however, the initial resorption lacunae
were not visible in periapical radiographs. Thus, it can be concluded that
the radiographic diagnosis is static, uncertain and not completely reli-
able. Computerized tomography and cone beam volumetric imaging have
been shown to increase sensitivity (Liedke et al., 2009); however, the
cost and high radiation exposure associated with these imaging tech-
244
Rody et al.
niques do not support their routine use for monitoring root resorption. On
the other hand, biomarkers have the potential to aid in screening, diagno-
sis and assessment of prognosis for tooth root conditions. These bio-
markers, if necessary, eventually could be converted into novel diagnos-
tic marker assays.
Molecular evidence for active root resorption might be detected
in the GCF of moving teeth. However, only a few biomarkers associated
with root resorption have been described in the literature (Mah and
Prasad, 2004; Balducci et al., 2007; Kereshanan et al., 2008; Tyrovola et
al., 2008; George and Evans, 2009). Cementum breakdown products in
the GCF may not be indicative of the permanent loss of root structure
because focal areas of cementum are resorbed and subsequently repaired
during tooth movement (Owman-Moll et al., 1995). On the other hand,
larger areas of dentin resorption do not repair, thus making the dentin
breakdown products in the GCF useful markers for root resorption.
Of the various dentin non-collagenous proteins, dentin phos-
phoproteins (DPP) and dentin sialoprotein (DSP) are the most abundant
proteins present within dentin. DPP have been detected in GCF of re-
Sorbing deciduous molars, non-resorbing incisors and resorbing incisors
during orthodontic treatment. The concentrations of these root-derived
molecules were higher significantly in GCF of teeth with resorbing roots
than in GCF from non-resorbing teeth (Mah and Prasad, 2004).
However, DPP are so highly phosphorylated and shielded by carbohy-
drates that they are not particularly antigenic, which makes the develop-
ment of antibodies for immunoassays particularly challenging.
Whether or not DSP is highly dentin specific is controversial be-
cause some investigators report that it is not found in ameloblasts, bone,
cartilage, soft tissues or other components of the oral tissues (Butler et
al., 1992), whereas a more recent report refutes this observation because
Western blots detected DSP in the extracts of rat long bone (Qin et al.,
2002). Despite the challenges and controversies, Balducci and colleagues
(2007) and Kereshanan and coworkers (2008) explored the presence of
dentin non-collagenous proteins in the GCF of patients undergoing or-
thodontic treatment and concluded that the use of DSP as biomarker was a
Suitable alternative for monitoring root resorption during tooth movement.
So far, the search for tooth-related biomarkers for early detection
of root resorption has focussed on proteins in GCF that are shed into the
periodontium as a consequence of the degenerative processes. This ap-
proach reflected the previously available technologies and has a low
245
Fluid-based Diagnostics
probability for success, similar to finding a needle in a haystack, because
it requires the separation, identification and testing of these single protein
candidate biomarkers individually. With the advances in technology, the
previous approach is being replaced by the new goal of finding panel of
proteins derived from the same pathological process that would consti-
tute a “diagnostic pattern” for the studied condition.
Nevertheless, until such time as wider surveys or proteins can be
conducted and tested, similar to the rate of tooth movement situation, the
balance of competitive agents may be useful to measure. Previous studies
have observed that periodontal ligament cells express more RANKL and
less OPG in cases of severe external apical root resorption (Yamaguchi
et al., 2006; Tyrovola et al., 2008, 2010; Nakano et al., 2010). This find-
ing recently was supported further by observations that the RANKL/
OPG ratio was higher statistically in the ‘GCF of human subjects with
severe root resorption than in the control subjects (George and Evans,
2009). Therefore, it seems worthwhile to investigate further whether or
not GCF concentrations of RANKL and OPG are related to the degree of
root resorption as well as the speed of tooth movement induced by ortho-
dontic treatment.
Monitor Periodontal Disease in the Presence of Orthodontic Appliances
Periodontitis occurs when inflammation spreads to the periodon-
tium, causing alveolar bone loss (Rai et al., 2008). When this bone loss is
excessive, the teeth can become loose and eventually fall out. The preva-
lence and severity of periodontal diseases tend to increase with age
throughout the world. Periodontal destruction is induced by the deleteri-
ous effects of inflammatory mediators occurring because of bacterial
plaque build-up around the tooth (Gaffen and Hajishengallis, 2008). Cer-
tain lifestyles, health conditions or states of health, systemic diseases and
genetics also are factors that can increase the severity of periodontitis
(Suzuki et al., 2008).
The periodontal disease activity is determined by a complex in-
terplay between the immune system and periodontal pathogens. It gener-
ally is accepted that periodontal health is compromised when orthodontic
appliances are worn (Forsberg et al., 1991; Heier et al., 1997). In fact,
the relationship between orthodontic procedures and periodontal status is
considered a challenge because some appliances can alter the subgingival
microbiota and induce inflammation (Ristic et al., 2008). The traditional
methods to detect periodontal disease (e.g., via X-ray images, probing depths
246
Rody et al.
and bleeding on probing measurements) are limited because although
these can indicate or suggest the presence of the condition, none provide
unequivocal confirmation of disease activity or prediction of disease outcome.
On the other hand, the quality of GCF reflects the progression of
periodontal disease and proves to be useful in early detection of perio-
dontitis (Suzuki et al., 2008). Recent research indicated that crevicular
MMP-9 may serve as biomarkers of periodontal disease and aid in early
detection of periodontitis (Bildt et al., 2009). MMPs are a gene family of
at least 25 proteolytic enzymes contributing to the remodeling of the ex-
tracellular matrix and are important in the physiologic remodeling of the
periodontium and its adaptation to mechanical forces, as previously de-
scribed. In periodontitis, a relative over-activity of MMPs results in the
breakdown of periodontal structures.
MMP-9 is derived predominantly from monocytes and macro-
phages, and its levels in GCF are higher in patients with periodontitis
(Rai et al., 2008). A recent study by Rody and associates (2011) using
microarray technique was carried out to evaluate if biomarkers of perio-
dontal remodelling are expressed differentially in the GCF of subjects
wearing fixed and removable orthodontic retainers for an extended pe-
riod of time. Higher concentrations of MMP-9 were found to be associ-
ated with higher percentages of sites with visible plaque in the incisor
region of subjects with fixed retainers in place (Fig. 8). The authors con-
cluded that the high loads of MMP-9 in the fixed retainer group may rep-
resent subclinical inflammation. Longitudinal studies are indicated to
investigate if this finding is a complicating factor for fixed orthodontic
retention over the long term.
Predict and Monitor Pain
Pain is a complex negative experience that shows large inter-
individual variation and many potential influences. However, pain is re-
ported by about 90% of individuals during orthodontic treatment
(Scheurer et al., 1996; Bergius et al., 2002) and, hence, is a common side
effect. To date, little is known about the specific mechanisms associated
with orthodontic pain (Krishnan, 2007); therefore, ideal candidate bio-
markers at best can be speculated. Nevertheless, biomarkers to predict
and monitor the pain experience during treatment could lead to improved
and individualized pain management. Evidence that pain experiences
should be avoided or minimized to prevent sensitization of the central
nervous system in those who may be susceptible genetically to pain (Slade
247
Fluid-based Diagnostics
- - Removable L
Fixed Retainer Retainer No Retainer
º
Mºº
Figure 8. Microarray images showing a higher intensity of the fluores-
cent signal that comes from the line (arrow) that represents the bio-
marker matrix metalloproteinase-9 (MMP-9) in the fixed retainer
group. GCF samples were collected from the lingual surfaces of the
lower incisors. -
et al., 2008) suggests further the potential importance of biomarkers for
Orthodontics.
Levels of some potential biomarkers have been measured in
GCF using ELISAs and have been associated positively with pain inten-
sity, as measured via the visual analogue scale (VAS) during orthodontic
procedures. One study investigated VAS scores and IL-13, Prostaglandin
E2 and Substance P in GCF from two molar sites per subject, with and
without a separator, at baseline and at one hour, one day and seven days
after delivery of the separator (Giannopoulou et al., 2006). Prostaglandin
E2 is known to be an essential mediator in bone turnover (Hatch, 2011)
and linked to hyperalgesia (Ferreira et al., 1978), while Substance P is a
pain mediator associated with activation of PDL cells in response to Or-
thodontic forces (Nicolay et al., 1990). In general, levels of IL-13, ProS-
taglandin E2 and Substance P in GCF at separator sites were higher than
control sites at all three time-points, showing a relative peak at one day
and a decrease by seven days post-placement. Pain intensity Scores
showed a similar trend, but by seven days post-placement of separators.
mean Scores were not higher significantly than baseline measures.
A second study investigated VAS scores and IL-13 levels in
GCF from distal sites of maxillary canines being moved distally via two
magnitudes of applied force (50 and 150 cm) and from control sites that
had no orthodontic appliances, over a two-month period (Luppanaporn-
larp et al., 2010). Mean IL-13 levels from distal sites of canines retracted
using 150 cl compared to control sites were found to be significantly
higher at 24 hours and two months after forces were applied. Mean pain

248
Rody et al.
scores were higher significantly for sides receiving higher compared to
lower forces at 24 hours. However, there were no significant differences
in mean amounts of tooth movement achieved by the two forces after
two months, so the investigators concluded that overall, lower force ap-
plication could result in similar tooth movement compared to the higher
force with less inflammation and pain.
In both studies, variations about means were high and inflamma-
tory responses associated with tooth movement and pain could not be
distinguished. However, these studies are early attempts to measure con-
ditions of tooth movement, pain and potential biomarkers. Future studies
should benefit from changes in approaches based on advancements in
proteomic techniques combined with knowledge gained about the genet-
ics and mechanisms of pain in other human conditions and associated
animal models (Doehring et al., 2011; Vasileiou et al., 2011).
CONCLUSIONS
An orthodontic appliance system that is capable of triggering os-
teoclast recruitment and bone remodeling with no root damage can be
considered “biologically efficient.” The idea is to develop “biomarker
profiles” to manage clinical interventions based on individual tissue re-
sponses in order to avoid unknown side effects.
The medical field is enthusiastic about the new breakthroughs
with the fast development of proteome research and MS technologies.
Hopefully in the near future, chairside portable devices to carry out de-
tection of biomarkers in oral fluids will become a reality in dentistry.
Finding ideal biomarkers and bringing these to the clinical setting are
ambitious aims, but history has proven that science is far-reaching; con-
sider the advances brought about through human DNA coding, vaccines
and cloning. The ultimate goal would be to provide “personalized bio-
logical orthodontic care” that can be defined as the systematic use of the
patient’s proteotype and metabolic profile to foster rapid and safe tooth
movement. The future of this field will depend on further validation of
Specific biomarkers and their incorporation into state-of-the-art assays
that are reliable, sensitive, specific and cost-effective for broad imple-
mentation in clinical practice.
REFERENCES
Aebersold R, Mann M. Mass spectrometry-based proteomics. Nature
2003;422:198-207.
249
Fluid-based Diagnostics
Alymani NA, Smith MD, Williams DJ, Petty RD. Predictive biomarkers
for personalised anti-cancer drug use: Discovery to clinical imple-
mentation. Eur J Cancer 2010:46:869-879.
Apajalahti S, Sorsa T, Railavo S, Ingman T. The in vivo levels of matrix
metalloproteinase-1 and -8 in gingival crevicular fluid during initial
Orthodontic tooth movement. J Dent Res 2003;82:10 18-1022.
Apweiler R, Aslanidis C, Deufel T, Gerstner A, Hansen J, Hochstrasser
D, Kellner R, Kubicek M, Lottspeich F, Maser E, Mewes HW, Meyer
HE, Mullner S, Mutter W, Neumaier M, Nollau P, Nothwang HG,
Ponten F, Radbruch A, Reinert K, Rothe G, Stockinger H, Tarnok A,
Taussig MJ, Thiel A, Thiery J, Ueffing M, Valet G, Vandekerckhove
J, Verhuven W, Wagener C, Wagner O, Schmitz G. Approaching
clinical proteomics: Current state and future fields of application in
fluid proteomics. Clin Chem Lab Med 2009;47:724–744.
Bacarese-Hamilton T, Ardizzoni A, Gray J, Crisanti A. Protein arrays for
serodiagnosis of disease. Methods Mol Biol 2004:264:271-283.
Balducci L, Ramachandran A, Hao J, Narayanan K, Evans C, George A.
Biological markers for evaluation of root resorption. Arch Oral Biol
2007:52:203-208.
Baughan LW, Robertello FJ, Sarrett DC, Denny PA, Denny PC. Salivary
mucin as related to oral Streptococcus mutans in elderly people. Oral
Microbiol Immunol 2000:15:10-14.
Bergius M, Berggren U, Kiliaridis S. Experience of pain during an or-
thodontic procedure. Eur J Oral Sci 2002; 110:92-98.
Bildt MM, Bloemen M, Kuijpers-Jagtman AM, Von den Hoff JW. Ma-
trix metalloproteinases and tissue inhibitors of metalloproteinases in
gingival crevicular fluid during orthodontic tooth movement. Eur J
Orthod 2009:31:529-535.
Bostanci N, Heywood W, Mills K, Parkar M, Nibali L, Donos N. Appli-
cation of label-free absolute quantitative proteomics in human gingi-
val crevicular fluid by LC/MS E (gingival exudatome). J Proteome
Res 2010;9:2191-2199.
Brezniak N, Wasserstein A. Root resorption after orthodontic treatment:
Part 1. Literature review. Am J Orthod Dentofacial Orthop 1993a;
103:62-66.
Brezniak N, Wasserstein A. Root resorption after orthodontic treatment:
Part 2. Literature review. Am J Orthod Dentofacial Orthop 1993b;
103:138-146.
250
Rody et al.
Buduneli N, Kinane DF. Host-derived diagnostic markers related to soft
tissue destruction and bone degradation in periodontitis. J Clin Perio-
dontol 2011:38 S1;85-105.
Bunikis J, Barbour AG. Laboratory testing for suspected Lyme disease.
Med Clin North Am 2002:86:31 1-340.
Burke JC, Evans CA, Crosby TR, Mednieks MI. Expression of secretory
proteins in oral fluid after orthodontic tooth movement. Am J Orthod
Dentofacial Orthop 2002; 121:310-315.
Burnette WN. “Western blotting”; Electrophoretic transfer of proteins
from socium dodecyl sulfate: Polyacrylamide gels to unmodified ni-
trocellulose and radiographic detection with antibody and radioiodi-
nated protein A. Anal Biochem 1981; 112:195-203.
Butler WT, Bhown M, Brunn JC, D’Souza RN, Farach-Carson MC,
Happonen RP, Schrohenloher RE, Seyer JM, Sommerman MJ, Foster
RA. Isolation, characterization and immunolocalization of a 53-kDal
dentin sialoprotein (DSP) Matrix 1992; 12:343-351.
Cantarella G, Cantarella R., Caltabiano M, Risuglia N, Bernardini R,
Leonardi R. Levels of matrix metalloproteinases 1 and 2 in human
gingival crevicular fluid during initial tooth movement. Am J Orthod
Dentofacial Orthop 2006; 130:568.e511-ejó6.
Capelli J Jr, Kantarci A, Haffajee A, Teles RP, Fidel R Jr, Figueredo
CM. Matrix metalloproteinases and chemokines in the gingival crevi-
cular fluid during orthodontic tooth movement. Eur J Orthod e-pub
March 9, 2011.
Castleberry CM, Rodicio LP, Limbach PA. Electrospray ionization mass
spectrometry of oligonucleotides. Curr Protoc Nucleic Acid Chem
2008; 10:Unit 10.2.
Chaerkady R, Pandey A. Applications of proteomics to lab diagnosis.
Ann Rev Pathol 2008;3:485-498.
Chang HS, Walsh LJ, Freer T.J. The effect of orthodontic treatment on
salivary flow, pH, buffer capacity and levels of mutans Streptococci
and lactobacilli. Aust Orthod J 1999; 15:229–234.
Chen R, Kanzaki H, Chiba M, Nishimura M, Kanzaki R, Igarashi K. Lo-
cal osteoprotegerin gene transfer to periodontal tissue inhibits
lipopolysaccharide-induced alveolar bone resorption. J Periodontal
Res 2008:43:237-245.
Choi YS, Choe LH, Lee KH. Recent cerebrospinal fluid biomarker stud-
ies of Alzheimer’s disease. Expert Rev Proteomics 2010;7:919-929.
251
Fluid-based Diagnostics
Colantonio DA, Chan DW. The clinical application of proteomics. Clin
Chim Acta 2005:357: 151-158.
Corthals GL, Wasinger VC, Hochstrasser DF, Sanchez JC. The dynamic
range of protein expression: A challenge for proteomic research.
Electrophoresis 2000:21:1104-11 15.
Court M, Selevsek N, Matondo M, Allory Y, Garin J, Masselon CD,
Domon B. Toward a standardized urine proteome analysis methodol-
ogy. Proteomics 2011; 11:1160–1171.
Denny P, Hagen FK, Hardt M, Liao L, Yan W, Arellanno M, Bassilian S,
Bedi GS, Boontheung P, Cociorva D, Delahunty CM, Denny T.
Dunsmore J, Faull KF, Gilligan J, Gonzalez-Begne M, Halgand F,
Hall SC, Han X, Henson B, Hewel J, Hu S, Jeffrey S, Jiang J, Loo JA,
Ogorzalek Loo RR, Malamud D, Melvin JE, Miroshnychenko O,
Navazesh M, Niles R, Park SK, Prakobphol A, Ramachandran P,
Richert M, Robinson S, Sondej M, Souda P, Sullivan MA, Takashima
J, Than S, Wang J, Whitelegge JP, Witkowska HE, Wolinsky L, Xie
Y, Xu T, Yu W, Ytterberg J, Wong DR, Yates JR III, Fisher SJ. The
proteomes of human parotid and submandibular/Sublingual gland
salivas collected as the ductal secretions. J Proteome Res 2008;7:
1994–2006.
Deschner J, Arnold B, Kage A, Zimmermann B, Kanitz V, Bernimoulin
JP. Suppression of interleukin-10 release from human periodontal
ligament cells by interleukin-1beta in vitro. Arch Oral Biol 2000;
45: 179-183.
Doehring A, Geisslinger G, Lotsch J. Epigenetics in pain and analgesia:
An imminent research field. Eur J Pain 2011:15:11-16.
Dominguez DC, Lopes R, Torres ML. Proteomics: Clinical applications.
Clin Lab Sci 2007:20:245–248.
Dommisch H, Vorderwulbecke S, Eberhard J, Steglich M, Jepsen S.
SELDI-TOF-MS of gingival crevicular fluid: A methodological ap-
proach. Arch Oral Biol 2009:54:803-809.
Domon B, Broder S. Implications of new proteomics strategies for biol-
ogy and medicine. J Proteome Res 2004;3:253–260.
Engvall E, Perlmann P. Enzyme-linked immunosorbent assay (ELISA):
Quantitative assay of immunoglobulin G. Immunochemistry 1971;8:
871-874.
252
Rody et al.
Fenn JB, Mann M, Meng CK, Wong SF, Whitehouse CM. Electrospray
ionization for mass spectrometry of large biomolecules. Science 189;
246:64–71.
Ferreira SH, Nakamura M, de Abreu Castros MS. The hyperalgesic ef-
fects of prostacyclin and prostaglandin E2. Prostaglandins 1978; 16:
31–37.
Flessig Y, Reichenberg E, Redlich M, Zaks B, Deutsch O, Aframian DJ,
Palmon A. Comparative proteomic analysis of human oral fluids ac-
cording to gender and age. Oral Dis 2010; 16:831-838.
Forsberg CM, Brattstrom V, Malmberg E, Nord CE. Ligature wires and
elastomeric rings: Two methods of ligation and their association with
microbial colonization of Streptococcus mutans and lactobacilli. Eur J
Orthod 1991; 13:416–420.
Gaffen Sl, Hajishengallis G. A new inflammatory cytokine on the block:
Re-thinking periodontal disease and the Th1/Th2 paradigm in the
context of Th17 cells and IL-17. J Dent Res 2008;87:817-828.
George A, Evans CA. Detection of root resorption using dentin and bone
markers. Orthod Craniofacial Res 2009:12:229-235.
Ghafari J, Jacobsson-Hunt U, Markowitz DL, Shofer FS, Laster LL.
Changes of arch width in the early treatment of Class II, division 1
malocclusions. Am J Orthod Dentofacial Orthop 1994; 106:496-502.
Giannobile WV, Beikler T, Kinney JS, Ramseier CA, Morelli T, Wong
DT. Saliva as a diagnostic tool for periodontal disease: Current state
and future directions. Periodontol 2000 2009:50:52-64.
Giannopoulou C, Dudic A, Kiliaridis S. Pain discomfort and crevicular
fluid changes induced by orthodontic elastic separators in children. J
Pain 2006;7:367-376.
Giannopoulou C, Mombelli, Tsinidou K, Vasdekos V, Kamma J. Detec-
tion of gingival crevicular fluid cytokines in children and adolescents
with and without fixed orthodontic appliances. Acta Odontol Scand
2008;66:169-173.
Gross JH. Mass Spectrometry: A Textbook. Berlin, New York: Springer 2004.
Gursoy UK, Kononen E, Uitto VJ, Pussinen PJ, Hyvarinen K, Suominen-
Taipale L, Knuuttila M. Salivary interleukin-1beta concentration and
the presence of multiple pathogens in periodontitis. J Clin Periodontol
2009:36:922–927.
253
Fluid-based Diagnostics
Han X, Aslanian A, Yates JR III. Mass spectrometry for proteomics.
Curr Opin Chem Biol 2008:12:483-490.
Hatch N. The biology of tooth movement: Current concepts on and ap-
plications to clinical practice. In: McNamara JA Jr, Hatch N, Kapila
SD, eds. Effective and Efficient Orthodontic Tooth Movement. Mono-
graph 48, Craniofacial Growth Series, Department of Orthodontics
and Pediatric Dentistry and Center for Human Growth and Develop-
ment, The University of Michigan, Ann Arbor 2011;73-91.
Heier EE, De Smit AA, Wijgaerts IA, Adriaens PA. Periodontal implica-
tions of bonded versus removable retainers. Am J Orthod Dentofacial
Orthop 1997; 112:607-616.
Henzel WJ, Billeci TM, Stults JT, Wong SC, Grimley C, Watanabe C.
Identifying proteins from two-dimensional gels by molecular mass
searching of peptide fragments in protein sequence databases. Proc
Natl Acad Sci USA 1993;90:50.11-5015.
Hu S, Loo JA, Wong DT. Human body fluid proteome analysis. Pro-
teomics 2006;6:6326-6353.
Huang Y, Ma YW, Tian LJ, Jin SM, Zhang J. Expression of MMPs in
gingival crevicular fluid of the rats in different age groups with ortho-
dontic appliances. [In Chinese.] Shanghai Kou Qiang Yi Xue 2008;
17:496-500.
Ingman T, Apajalahti S, Mantyla P, Savolainen P, Sorsa T. Matrix metal-
loproteinase-1 and -8 in gingival crevicular fluid during orthodontic
tooth movement: A pilot study during 1 month of follow-up after
fixed appliance activation. Eur J Orthod 2005:27:202-207.
Iwasaki LR, Crouch LD, Tutor A, Gibson S, Hukmani N. Marx DB,
Nickel JC. Tooth movement and cytokines in gingival crevicular fluid
and whole blood in growing and adult subjects. Am J Orthod Dento-
facial Orthop 2005;128:483-491.
Iwasaki LR, Gibson CS, Crouch LD, Marx DB, Pandey JP, Nickel JC.
Speed of tooth movement is related to stress and IL-1 gene polymor-
phisms. Am J Orthod Dentofacial Orthop 2006;130:698.e691-e699.
Iwasaki LR, Haack JE, Nickel JC, Reinhardt RA, Petro TM. Human in-
terleukin-1 beta and interleukin-1 receptor antagonist secretion and
velocity of tooth movement. Arch Oral Biol 2001;46:185-189.
Iwasaki LR, Nickel JC. Markers of paradental tissue remodelling in the
gingival crevicular fluid of orthodontic patients. In: Krishnan V, Da-
254
Rody et al.
vidovitch Z, eds. Biological Mechanisms of Tooth Movement. Chich-
ester, UK:Wiley-Blackwell 2009; 123-142.
James P. Protein identification in the post-genome era: The rapid rise of
proteomics. Q Rev Biophys 1997:30:279-331.
James P, Quadroni M., Carafoli E, Gonnet G. Protein identification by
mass profile fingerprinting. Biochem Biophys Res Commun 1993;
| 95:58–64.
Jensen ON, Podtelejnikov AV, Mann M. Identification of the compo-
nents of simple protein mixtures by high-accuracy peptide mass map-
ping and database searching. Anal Chem 1997;69:4741-4750.
Joos TO, Schrenk M, Hopfl P, Kroger K, Chowdhury U, Stoll D, Schor-
ner D, Durr M, Herick K, Rupp S, Sohn K, Hammerle H. A microar-
ray enzyme-linked immunosorbent assay for autoimmune diagnostics.
Electrophoresis 2000:21:2641-2650.
Karas M, Hillenkamp F. Laser desorption ionization of proteins with mo-
lecular masses exceeding 10,000 daltons. Anal Chem 1988;60:2299-
2301.
Kavadia-Tsatala S, Kaklamanos EG, Tsalikis L. Effects of orthodontic
treatment on gingival crevicular fluid flow rate and composition:
Clinical implications and applications. Int J Adult Orthod Orthognath
Surg 2002; 17:191-205.
Kawarizadeh A, Bourauel C, Gotz W, Jager A. Early responses of perio-
dontal ligament cells to mechanical stimulus in vivo. J Dent Res 2005;
84:902-906.
Kereshanan S, Stephenson P, Waddington R. Identification of dentine
sialoprotein in gingival crevicular fluid during physiological root resorp-
tion and orthodontic tooth movement. Eur J Orthod 2008:30:307-314.
King GJ, Noxon SJ, Rody WJ Jr. Osteoclast mechanisms during tooth
movement. In: Davidovitch Z, ed. Biological Mechanisms of Tooth
Movement and Craniofacial Adaptation. Boston, MA: Harvard Soci-
ety for the Advancement of Orthodontics 2000;81-89.
Kinney JS, Morelli T, Braun T, Ramseier CA, Herr AE, Sugai JV, Shel-
burne CE, Rayburn LA, Singh AK, Giannobile WV. Saliva/pathogen
biomarker signatures and periodontal disease progression. J Dent Res
2011;90:752–758.
Krishnan V. Orthodontic pain: From causes to management. A review.
Eur J Orthod 2007:29:170-179.
255
Fluid-based Diagnostics
Lara-Carillo E., Montiel-Bastida NM, Sanchez-Peres L., Alanis-Tavira J.
Effect of orthodontic treatment on saliva, plaque and the levels of
Streptococcus mutans and Lactobacillus. Med Oral Patol Oral Cir
Bucal 2010; 15:e924-eg29.
Liedke GS, da Silveira HE, da Silvira HL, Dutra V, de Figueiredo J.A.
Influence of voxel size in the diagnostic ability of cone-beam tomo-
graphy to evaluate simulated external root resorption. J Endod 2009;
35:233-235.
Lin Y, Huang R, Cao X, Wang SM, Shi Q, Huang RP. Detection of mul-
tiple cytokines by protein arrays from cell lysate and tissue lysate.
Clin Chem Lab Med 2003:41: 139-145.
Loo JA, Yan W, Ramachandran P, Wong DT. Comparative human sali-
vary and plasma proteomes. J Dent Res 2010;89:1016–1023.
Luppanapornlarp S, Kajii TS, Surarit R, Iida J. Interleukin-1beta levels,
pain intensity, and tooth movement using two different magnitudes of
continuous orthodontic force. Eur J Orthod 2010:32:596-601.
MacPhee DJ. Methodological considerations for improving Western blot
analysis. J Pharmacol Toxicol Methods 2010;61:171-177.
Mah J, Prasad N. Dentine phosphoproteins in gingival crevicular fluid
during root resorption. Eur J Orthod 2001:26:25-30.
Malamud D. Saliva as a diagnostic fluid. Dent Clin North Am 2011:55:
159-178.
Marcaccini AM, Amato PA, Leao FV, Gerlach RF, Ferreira JT. Myelop-
eroxidase activity is increased in gingival crevicular fluid and whole
saliva after fixed orthodontic appliance activation. Am J Orthod Den-
tofacial Orthop 2010;138:613-616.
McDermott U, Downing JR, Stratton MR. Genomics and the continuum
of cancer care. N Engl J Med 2011;364:340-350.
Mikulewicz M, Chojnacka K. Release of metal ions from orthodontic
appliances by in vitro studies: A systematic literature review. Biol
Trace Elem Res 2011; 139:241–256.
Mikulewicz M, Chojnacka K. Trace metal release from orthodontic ap-
pliances by in vivo studies: A systematic literature review. Biol Trace
Elem Res 2010; 137:127-138.
Mirabella AD, Artun J. Risk factors for apical root resorption of maxil-
lary anterior teeth in adult orthodontic patients. Am J Orthod Dento-
facial Orthop 1995;108:48-55.
256
Rody et al.
Mischak H, Delles C, Klein J, Schanstra JP. Urinary proteomics based on
capillary electrophoresis-coupled mass spectrometry in kidney dis-
ease: Discovery and validation of biomarkers and clinical application.
Adv Chronic Kidney Dis 2010; 17:493-506.
Mogi M, Otogoto J, Ota N, Togari A. Differential expression of RANKL
and osteoprotegerin in gingival crevicular fluid of patients with perio-
dontitis. J Dent Res 2004;83:166-169.
Morris HR, Panico M, Barber M, Bordoli RS, Sedgwick RD, Tyler A.
Fast atom bombardment: A new mass spectrometric method for pep-
tide sequence analysis. Biochem Biophys Res Commun 1981; 101:
623-631. y
Nakano Y, Yamaguchi M., Fujita S, Asano M, Saito K, Kasai K. Expres–
sions of RANKL, RANK and M-CSF/c-fms in root resorption lacu-
nae in rat molar by heavy orthodontic force. Eur J Orthod e-pub 2010
Sep 10, doi:10.1093/ejo/cjq068.
Ngo LH, Veith PD, Chen YY, Chen D, Darby IB, Reynolds EC. Mass
spectrometric analyses of peptides and proteins in human gingival
crevicular fluid. J Proteome Res 2010;9:1683-1693.
Nicolay OF, Davidovitch Z, Shanfeld JL, Alley K. Substance P im-
munoreactivity in periodontal tissues during orthodontic tooth move-
ment. Bone Miner 1990; 11:19-29.
Nishijima Y, Yamaguchi M, Kojima T, Aihara N, Nakajima R, Kasai K.
Levels of RANKL and OPG in gingival crevicular fluid during ortho-
dontic tooth movement and effect of compression force on releases
from periodontal ligament cells in vitro. Orthod Craniofacial Res
2006;9:63-70.
Oellerich M. Enzyme immunoassays in clinical chemistry: Present status
and trends. J Clin Chem Clin Biochem 1980; 18:197-208.
Okrojek R, Grus FH, Matheis N, Kahaly GH. Proteomics in autoimmune
thyroid eye disease. Horm Metab Res 2009:41:465-470.
Owman-Moll P, Kurol J, Lundgren D. Repair of orthodontically induced
root resorption in adolescents. Angle Orthod 1995;65:403-408.
Pietrowska M, Marczak L, Polanska J, Nowicka E, Behrent K, Tar-
nawski R, Stobiecki M, Polanski A, Widlak P. Optimizing of
MALDI-ToF-based low-molecular-weight serum proteome pattern
analysis in detection of breast cancer patients: The effect of albumin
removal on classification performance. Neoplasma 2010:57:537-544.
257
Fluid-based Diagnostics
Pirmohamed M. Acceptance of biomarker-based tests for application in
clinical practice: Criteria and obstacles. Clin Pharmacol Ther 2010;
88:862-866.
Prabhakar U, Eirikis E, Reddy M, Silvestro E, Spitz S, Pendley C II,
Davis HM, Miller BE. Validation and comparative analysis of a mul-
tiplexed assay for the simultaneous quantitative measurement of
Th1/Th2 cytokines in human serum and human periperal blood
mononuclear cell culture supernatants. J Immunol Methods 2004;
291 :27–38.
Qin C, Brunn JC, Cadena E, Ridall A, Tsujigiwa H, Nagatsuka H, Nagai
N, Butler WT. The expression of dentin sialophosphoprotein gene in
bone. J Dent Res 2002;81:392–394.
Rai B, Kharb S, Jain R, Anand SC. Biomarkers of periodontitis in oral
fluids. J Oral Sci 2008:50:53-56.
Ren Y, Hazemeijer H, de Haan B, Qu N, de Vos P. Cytokine profiles in
crevicular fluid during orthodontic tooth movement of short and long
durations. J Periodontol 2007;78:453-458. -
Ren Y, Vissink A. Cytokines in crevicular fluid and orthodontic tooth
movement. Eur J Oral Sci 2008; 116:89-97.
Reynolds SJ, Muwonga J. OraQuick ADVANCE Rapid HIV-1/2 anti-
body test. Expert Rev Mol Diagn 2004;4:587-591.
Ristic M, Vlahovic Svabic M, Sasic M, Zelic O. Effects of fixed ortho-
dontic appliances on subgingival microflora. Int J Dent Hyg 2008;6:
129-136.
Rody WJ Jr, Akhlaghi H, Akyalcin S, Wiltshire WA, Wijegunasinghe M,
Filho GN. Impact of orthodontic retainers on periodontal health status
assessed by biomarkers in gingival crevicular fluid (GCF). Angle Or-
thod 2011;81:1083–1089.
Rody WJ Jr, King GJ, Gu G. Osteoclast recruitment to sites of compres-
sion in orthodontic tooth movement. Am J Orthod Dentofacial Orthop
2001;120:477-489.
Schaub S, Wilkins JA, Antonovici M, Krokhin O, Weiler T, Rush D,
Nickerson P. Proteomic-based identification of cleaved urinary beta2-
microglobulin as a potential marker for acute tubular injury in renal
allografts. Am J Transplant 2005;5:729-738.
Scheurer PA, Firestone AR, Burgin WB. Perception of pain as a result of
orthodontic treatment with fixed appliances. Eur J Orthod 1996;18:
349-357.
258
Rody et al.
Shafer MW, Mangold L., Partin AW, Haab BB. Antibody array profiling
reveals serum TSP-1 as a marker to distinguish benign from malig-
nant prostatic disease. Prostate 2007;67:255-267.
Sharon D, Chen R, Snyder M. Systems biology approaches to disease
marker discovery. Dis Markers 2010:28:209-224.
Slade GD, Diatohenko L, Ohrbach R, Maixner W. Orthodontic treatment,
genetic factors and risk of temporomandibular disorder. Semin Or-
thod 2008; 14:146-156.
Socransky SS, Haffajee AD. Periodontal microbial ecology. Periodontol
2000 2005:38:135-187.
Spielmann N, Wong D. Saliva: Diagnostics and therapeutic perspectives.
Oral Dis 2011; 17:345-354.
Spisak S, Tulassay Z, Molnar B, Guttman A. Protein microchips in bio-
medicine and biomarker discovery. Electrophoresis 2007:28:4261-
4273.
Streckfus C, Bigler L, Tucci M, Thigpen JT. A preliminary study of
CA 15-3, c-erbB-2, epidermal growth factor receptor, cathepsin-D,
and p53 in saliva among women with breast carcinoma. Cancer Invest
2000:18:101-109:
Stryer L. Biochemistry, 4th ed. New York: WH Freeman 1995.
Suzuki M, Ishihara Y, Kamiya Y, Koide M, Fuma D, Fujita S, Matsu-
mura Y, Suga T, Kamei H, Noguchi T. Soluble interleukin-1 receptor
type II levels in gingival crevicular fluid in aggressive and chronic pe-
riodontitis. J Periodontol 2008;79:495-500.
Takahashi I, Nishimura M, Onodera K, Bae JW, Mitani H, Okazaki M,
Sasano Y, Mitani H. Expression of MMP-8 and MMP-13 genes in the
periodontal ligament during tooth movement in rats. J Dent Res 2003;
82:646–651.
Takahashi I, Onodera K, Nishimura M, Mitnai H, Sasano Y, Mitani H.
Expression of genes for geletinases and tissue inhibitors of metallo-
proteinases in periodontal tissues during orthodontic tooth movement.
J Mol Histol 2006:37:333-342.
Torno M, Vollmer M, Beck CK. West Nile virus infection presenting as
acute flaccid paralysis in an HIV-infected patient: A case report and
review of the literature. Neurology 2007;68:e5-e7.
Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins
from polyacrylamide gels to nitrocellulose sheets: Procedure and
some applications. Proc Natl Acad Sci USA 1979;76:4350-4354.
259
Fluid-based Diagnostics
Tyrovola JB, Perrea D, Halazonetis DJ, Dontas I, Vlachos IS, Makou M.
Relation of soluble RANKL and osteoprotegerin levels in blood and
gingival crevicular fluid to the degree of root resorption after ortho-
dontic tooth movement. J Oral Sci 2010:52:299-3 | 1.
Tyrovola JB, Spyropoulos MN, Makou M, Perrea D. Root resorption and
the OPG/RANKL/RANK system: A mini review. J Oral Sci 2008:50:
367–376.
Uematsu S, Mogi M., Deguchi T. Increase of transforming growth factor-
beta-1 in gingival crevicular fluid during human orthodontic tooth
movement. Arch Oral Biol 1996:41: 1091–1095.
Van Weemen BK, Schuurs AH. Immunoassay using antigen-enzyme
conjugates. FEBS Lett 1971; 15:232-236.
Vasileiou I, Giaginis C, Klonaris C, Theocharis S. Insight into pain-
inducing and related gene expression: A challenge for development of
novel targeted therapeutic approaches. Fundam Clin Pharmacol 2011;
25:48–62.
Voller A, Bidwell D, Bartlett A. The Enzyme Linked Immunosorbent As-
say (ELISA): A Guide with Abstracts of Microplate Applications.
London: Dynatech Laboratories Inc., 1979.
Waddington RJ, Embery G. Proteoglycans and orthodontic tooth move-
ment. J Orthod 2001:28:28.1–290.
Walter G, Bussow K, Lueking A, Glokler J. High-throughput protein
arrays: Prospects for molecular diagnostics. Trends Mol Med 2002:8:
250–253.
Wang YS, Cao R, Jin H, Huang YP, Zhang XY, Cong Q, He YF, Xu CJ.
Altered protein expression in serum from endometrial hyperplasia and
carcinoma patients. J Hematol Oncol 2011;4:15.
Wilson TG, Gregory RL. Clinical effectiveness of fluoride-releasing
elastomers: I. Salivary Streptococcus mutans numbers. Am J Orthod
Dentofacial Orthop 1995;107:293–297.
Wong DT. Salivary diagnostics powered by nanotechnologies, pro-
teomics and genomics. J Am Dent Assoc 2006a, 137:313–321.
Wong DT. Towards a simple, saliva-based test for the detection of oral
cancer ‘oral fluid (saliva), which is the mirror of the body, is a perfect
medium to be explored for health and disease surveillance.” Expert
Rev Mol Diagn 2006b;6:267–272.
260
Rody et al.
Yamaguchi M., Aihara N, Kojima T, Kasai K. RANKL increase in com-
pressed periodontal ligament cells from root resorption. J Dent Res
2006:85:751–756.
Yamaguchi M., Kasai K. Inflammation in periodontal tissues in response
to mechanical forces. Arch Immunol Ther Exp (Warsz) 2005:53:388-
398.
Yan W, Apweiler R, Balgley BM, Boontheung P, Bundy JL, Cargile BJ,
Cole S, Fang X, Gonzalez-Begne M, Griffin TJ, Hagen F, Hu S,
Wolinsky LE, Lee CS, Malamud D, Melvin JE, Menon R, Mueller M,
Qiao R, Rhodus NL, Sevinsky JR, States D, Stephenson JL, Than S,
Yates JR, Yu W, Xie H, Xie Y, Omenn GS, Loo JA, Wong DT. Sys-
tematic comparison of the human saliva and plasma proteomes. Pro-
teomics Clin Appl 2009;3:116-134.
Yates JR III, Eng JK, McCormack AL, Schieltz D. Method to correlate
tandem mass spectra of modified peptides to amino acid sequences in
the protein database. Anal Chem 1995;67:1426-1436.
Zaluzec EJ, Gage DA, Watson JT. Matrix-assisted laser desorption ioni-
zation mass spectrometry: Applications in peptide and protein charac-
terization. Protein Expr Purif 1995;6:109-123.
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262
SURESMILE": AN EIGHT-YEAR
CLINICAL PERSPECTIVE
Ronald J. Snyder
ABSTRACT
As the original SureSmile" user in the upper Midwest with over 625 SureSmile"
finishes, the author gives insights into the system’s contributions to advancing
orthodontic technology in terms of financial usability, clinical efficiency and
clinical outcomes. A university-based outcome assessment study performed on
consecutively treated samples of the author's finished SureSmile” cases con-
trasted with matched groups of cases treated by the author conventionally is
reviewed. Clinical examples are shown that display the technology’s diagnostic
advancements as well as diagnostic and treatment concepts that enable the effi-
cient management of a robotically bent copper nickel titanium finishing wire.
Learning objectives of this chapter include: insights into financial us-
ability, clinical efficiency and clinical outcomes of SureSmile” technology; the
presentation of university-based outcome assessment results from SureSmile”
treated cases in the author’s practice; and the presentation of clinical cases that
show diagnosis and treatment planning advancements offered by SureSmile”
technology.
KEY words: SureSmile”, clinical efficiency, technology, shape memory alloy
wires, outcome assessment
As an early user, I was introduced to SureSmile” in 2001 and be-
came the company’s seventh beta tester in 2003. The founder and top
executives invited me to become a member of the SureSmile” Clinical
Advisory Board from 2004-2008. My SureSmile” experience has been
showcased as a previous presenter at the Moyers Symposium and at two
annual sessions of the American Association of Orthodontists (2005 and
2011).
Eight years of clinical experience and over 625 SureSmile” com-
pleted cases have given me the depth to cooperate with the publication of
two articles on my finished outcomes: Saxe and associates (2010) and
Alford and colleagues (2011). A third study currently is in progress as a
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SureSmile": A Clinical Perspective
thesis project at the University of Michigan. These three investigations
provide clinical outcome studies contrasting my SureSmile" treatment
with my conventional treatment.
The SureSmile" technique has been described previously (Sny-
der, 2006). As a review, a light scan captures a baseline of the dentition
from the pretreatment plaster model and after the brackets are in place.
Then, generally after the teeth have been leveled and aligned, a clinical
light scan (or a cone-beam radiograph) is repeated in a 20 to 30 minute
clinical procedure that captures in real time the dentition and the occlu-
sion. These data then are sent via a DSL line to the Orametrix" corporate
headquarters in Richardson, TX, where the digital images are cleaned
and made ready for the orthodontist to detail the teeth into their final vir-
tual positions. Once the targeted tooth positions are completed in their
virtual state, the digital lab performs wire fabrication through applied
robotics. All types of archwires are possible with this system; however,
the power of the system is realized with fully adjusted shape memory
copper nickel titanium (NiTi) archwires.
My SureSmile" finishes since 2004 are distributed in Figure 1.
The distribution of SureSmile" finishes peaked in my fourth year and has
declined slowly to approximately 25% of the finishes in my practice. The
reason for the drop off is related, in part, to the Orametrix" contractual
obligations concerning ongoing equipment purchase or lease, software,
training, service, supply and minimum cases fee requirements that create
financial and operational limitations. To make prudent decisions con-
cerning software and any other transformation that has a long-term im-
pact on your practice, staff and patients require due diligence, care, nego-
tiation and treatment, operational and financial analysis based on actual
and proven results. Additionally, a clinical factor that underlies my
SureSmile” utilization is the inherent limitation of any archwire (or
bracket) defined system to be able treat the complex orthodontic problem
driven by orthopedic disproportions. Over the last eight years, each of
these factors have had an effect on the distribution in my SureSmile”
finished cases as they interplay with the return on investment (cost ver-
sus quality and efficiency).
Proposed benefits are made with any orthodontic technology
product. I have identified five primary benefits proposed by SureSmile”
to the orthodontic community:
• Improved diagnostics;
• Increased efficiency;
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Snyder
160
140
120
100
80
60
40
20
‘04 ‘O5 06 07 ‘08 ‘09 “10
Figure 1. The author's SureSmile" finishes 2004-2010.
• Faster treatment:
* Better finishes; and
* 100% practice conversion.
PROPOSED BENEFITS OF SURESMILE”
Improved Diagnostics
Significant strides have been made in three-dimensional (3D)
technology in the late 20th and early 21st centuries. Diagnostic capability
has been enhanced greatly with 3D technology. SureSmile" most cer-
tainly has played a leading role in the ease of software utilization, clarity
of the visual images and the development of software tools at the dis-
posal of the clinical orthodontist to enhance diagnostic information and
treatment planning.
Increased Efficiency
SureSmile" copper NiTi wires with proactive, targeted wire
planning produce significantly less round tripping than occurs with con-
Ventional straight wire systems. The over-seated band in Figure 2 would
be elevated when using a conventional straight wire appliance, creating a
required correction to level the marginal ridges. The Sure-Smile" copper
NiTi wire shown in Figure 2 has compensating bends placed robotically
as determined by ideal tooth position. Retroactive wire bending is elimi-
nated with this proactive method of treatment that avoids round tripping.
The shape-memory property of copper NiTi is leveraged. Additionally,

265
SureSmile": A Clinical Perspective
Figure 2. An over-seated band shown with a SureSmile" copper NiTi
wire with robotically placed compensating bends.
this system is efficient clinically in that there is no need for chair-side
wire bending.
Faster Treatment
The proposed benefit of faster treatment suggests that the ortho-
dontist can create more clinic capacity, enabling more patients to be seen
in the practice. SureSmile" also suggests to its potential orthodontic cus-
tomers that the “SureSmile" orthodontists” can distinguish their practice
from “non-SureSmile" competitors” on claims that their product permits
faster treatment without diminishing treatment outcomes. The technology
is aimed at having time be the orthodontist’s friend as a method of clini-
cal efficiency and as a marketing tool. Time in an orthodontic setting.
however, can be the orthodontist’s enemy when the time factor takes
precedent over standard-of-care requirements. With technology that
promises faster treatment, there is a potential trap of being wedged be:
tween an orthodontist’s promise of speed and his/her judgment and abil-
ity to deliver quality care.
In my eight years using SureSmile", the annual average distribu-
tion of the months in braces with SureSmile" has leveled at just over 13
months (Fig. 3) due to my ability to simplify the system through im-
proved case selection that recognizes the limitations of continuous arch-
wire mechanics when applied to orthodontic cases that are composed of

266
Snyder
18
16
14
12
10
‘04 ‘O5 06 07 ‘08 ‘09 “10
Figure 3. Annual average distribution of the months in braces
with SureSmile" has leveled at just over 13 months.
more complex orthopedic problems. Also, impacting this faster treatment
time is a dedicated staff with extensive SureSmile" initial and recurring
training.
Alford and coworkers (2011) analyzed a sample of 132 consecu-
tively finished, cooperative patients treated without extractions in my
practice. Variables studied include: time, the discrepancy index (Ameri-
can Board of Orthodontics, 2008) and the Cast Radiographic Evaluation
(CRE) scoring (American Board of Orthodontics, 2008), otherwise
known as the ABO’s Objective Grading System. This study had case
Selection criteria of:
* Second molars erupted and in occlusion;
* No dental agenesis:
* No documented compliance problems;
• All patients treated to an optimal result in the opinion
of the treating orthodontist; and
* No extractions performed.
The finished models were selected blindly (as to treatment
method) by the practicing orthodontist (the author) to meet the above
criteria. Once a finished case was selected, pre- and post-treatment mod-
els and radiographs were sent blindly to the investigator to determine
individual discrepancy indices and final model CRE scores (the lower the
score, the better the outcome). The method of treatment (conventional or
SureSmile") was not revealed until treatment notes were sent after grad-

267
SureSmile": A Clinical Perspective
ing was completed. The investigator was blinded as to method of treat-
ment until the time variable was studied by matching the models and ra-
diographs with the individual treatment notes.
The findings of the Alford study (2011) showed that SureSmile"
statistically had improved treatment times by seven months. Importantly,
the conventional treatment (n = 63) had 51% male patients while the
SureSmile" treatment (n = 69) had 39% male patients, a finding that may
have impacted the speed of treatment in that males have been shown to
have increased treatment times and higher CRE scores (Deguchi et al.,
2005).
Better Finishes
The Discrepancy Index (DI; a degree of difficulty measure) as
measured by the ABO standards in the Alford study (2011) showed that
the SureSmile" group with a mean of 13.3 had significantly lower DI
mean scores compared to the conventional mean of 15.8. This modest
difference perhaps had a bearing on the outcomes as other studies have
shown that the higher the DI at the beginning of treatment, the higher the
CRE scoring at the end of treatment (Vu et al., 2008). This sample, both
conventional and SureSmile", is considered as having a moderate to mild
degree of difficulty. The American Board of Orthodontics requires that
three of the required six case reports to each have a DI score of 20 or
greater.
In the Alford study (2011), the ABO’s CRE model scoring was
performed blindly on all 132 finished sets of dental casts. To determine
the CRE scoring, all eight ABO grading criteria were utilized (Fig. 4).
It is important to remember that, in general, a case report that
scores more than 30 points will fail the clinical portion of the American
Board of Orthodontics exam. A case report that scores less than 25 points
generally will pass that portion of the clinical examination.
The results of the Alford study (2011) revealed a mean CRE for
the SureSmile” sample of 18.5 while the conventional sample was scored
to a 20.8. A strong trend was observed toward SureSmile” producing
lower total CRE scores in significantly less treatment time. The lower
total CRE scores were not different significantly than the conventional
treatment. Again, 51% of the conventional group were males compared
to 39% of the SureSmile” group and 62% of the conventional group were
treated with two phases while 42% of the SureSmile” group were treated
with two phases. The higher percentage of two-phase treatment in the con-
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Snyder
Marginal Ridges
D10
§
Overjet Overjet Root angulation
Figure 4. American Board of Orthodontics grading criteria used to determine
cast radiograph evaluation scoring.
Ventional sample is consistent with the higher discrepancy index scores
recorded. The individual cast radiograph scoring showed significant
difference in the alignment rotation criteria, in that cases treated with
SureSmile" improved significantly in comparison to conventional treat-
ment (Fig. 5).
Finally, in all other measures there was no difference between
the conventional and SureSmile" findings; however, there was a trend
toward the conventionally treated group having improved root angulation
Scores compared to the SureSmile" treated group (Table 1).
100% Practice Conversion
Finally, the claim that orthodontic practices can be converted to
100% SureSmile" should be evaluated carefully in light of the patient’s
comprehensive orthodontic problem list. SureSmile" primarily is tooth
movement technology. Clinicians must be reminded that most orthodon-
tic cases have a skeletal component that cannot be addressed by tooth
movement alone. Professionally, to justify the expense of using this
technology, I am looking for orthodontic patients who can be treated to
an ABO-quality finish in 13 months. Typically, traditional treatment is
utilized versus this technology when concomitant skeletal problems require

269
SureSmile": A Clinical Perspective
ABO Mean CRE Scores
5 Conventional
SureSmile
AR MR BL OJ OC OR IC RA
ABO Cast-Radiograph Score Components
Figure 5. Results of individual cast radiograph scoring from
the study of Alford and coworkers (2011) showing significant
difference in alignment and rotations (AR) and interproximal
contact (IC) criteria.
Table 1. CRE scores indicating a trend toward improved root angulation
scores for conventionally treated group versus SureSmile" treated group.
Range and mean + standard error (SE) distributions for CRE scores.
Conventional (n = 63) SureSmile (n = 69)
Min || Max || Mean (SE) | Min || Max || Mean (SE
Age (start of treatment) 12 60 17.8 (0.8) 13 60 18.1 (0.9)
DI (discrepancy index) 3 40 15.8 (0.9) 1 33 13.2 (0.9
AR (alignment and rotations) () 10 4.0 (0.3) () 7 2.7 (0.2)
MR (marginal ridges) () 12 5.2 (0.3) () 16 5.3 (0.4
BL (buccal-lingual) () 6 2.7 (0.2) () 8 2.7 (0.2)
OJ (overjet) () 9 2.8 (0.2) () 10 2.7 (0.3
OC (occlusal contacts) () 12 2.2 (0.3) () 10 2.0 (0.3
OR (occlusal relationship) () 10 2.3 (0.3) () 7 1.6 (0.2)
IC (interproximal contacts) () 5 0.5 (0.1) () 2 0.2 (0.1
RA (root angulation) () 7 0.9 (0.2) () 5 1.3 (0.2)
Total CRE score 9 38 20.8 (0.8) 6 38 18.5 (1.0
Tx time: total 14 71 32.0 (1.6) 7 78 22.7 (1.5)
Tx time: in braces alone 12 38 23.6 (0.7) 7 35 16.7 (0.8)
Tx time: in braces-only patients 14 31 23.0 (1.0) 7 31 15.8 (1.0)

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Snyder
excessive time management. For instance, a Class II case requiring ex-
tensive headgear or a Herbst appliance, extraction cases with underlying
skeletal problems or skeletal open bites that require extensive dental and
skeletal control all marginalize Virtual wire technology.
My personal case selection criterion includes:
• Non-extraction
Class I
o Crowding
o Constricted
o Open bites under vertical control
o Deep bite – with bite opening auxiliaries
Class II/III — mild with compliance
Adults (non-extraction)
• Surgical
An example from the SureSmile" treated sample is shown in
Figure 6. This patient, who had earlier maxillary expansion (an example
of a skeletal problem being treated without the reliance on wire technol-
ogy alone), has a mild Class II malocclusion and a mild deep bite. After
3.5 months of light wire leveling with precision lingual arches in place
along with cervical headgear, the patient was scanned (Fig. 7). Two sets
of copper NiTi wires (0.016” x 0.022” and 0.019.” x 0.025”) were utilized
over seven months concomitant with cervical headgear for Class II cor-
rection. Nearly all of my SureSmile” cases receive this sequence and
number of wires (two sets). His final models were scored (12 DI and a 16
CRE) after a total treatment time of 12.5 months (Fig. 8).
A DISTINCT ADVANTAGE OF VIRTUALLY PLANNED
SHAPE MEMORY ARCHWIRES
Surgical treatment is an area where SureSmile” offers a distinct
advantage. The simulated positioning of the orthognathic 3D models in-
cludes both the virtual planning of the surgical move and the subsequent
design of the final shape memory archwires. Three-dimensional planning
capitalizes fully on the mechanical properties of the copper NiTi wires
during the Rapid Acceleratory Phenomenon (RAP; Wilcko et al., 2001;
Cohen et al., 2010) immediately post-surgery. Commonly, Surgical pa-
tients wear vertical elastics post-surgery. With SureSmile” wires in
place, post-surgical elastics direct the dentition to its predetermined fin-
ished position more efficiently through virtually designed, robotically bent
271
SureSmile": A Clinical Perspective
Figure 6. Initial records for 14-year-old patient with mild Class II occlusion and
mild deep bite. Patient was included in SureSmile" treated sample.
copper NiTi shape memory wires. Conventionally, the orthodontist can-
not consider retroactive wire manipulation until several months into the
RAP phase, which can delay treatment significantly.
The example in Figure 9 shows a patient who had previous
mixed dentition treatment to align non-aesthetic maxillary canines. At 15
years of age, this patient’s mandibular growth was confirmed to be close
to cessation. Seven months after braces were placed and light wire align-
ing completed, the patient was scanned with the SureSmile" OraScanner,
virtual models were created and a treatment simulation performed by the

272
Snyder
Figure 7. Photos of patients shown in Figure 6 taken on the day of the scanning
appointment.
Figure 8. Comparison of pre-scanning and post-treatment photos.





273
SureSmile": A Clinical Perspective
Figure 9. Pre-scanning photos. Patient was treated previously with 14 months of
upper arch treatment for high canines.
author. The virtual planning (Figs. 10–11) reveals the power of 3D simu-
lation; after the patient’s mandible virtually was auto-rotated to ideal
(center of rotation at the center of the condyle), her maxilla was impacted
differentially to match the mandibular position. Then the anterior denti-
tion could be assessed relative to the rotational changes that occur with
Surgical skeletal rotation.

274
Snyder
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ºn-º-º-º: 199- H º º º =: º º
*IºT lºſ Eſº Bºſº BTETE
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F cºnvº ºccº Tº ſº sº
For Hºp, press F1 sºmeºmºmºſº, swººsººges
Figure 10. SureSmile" virtual planning software shows the power of using 3D
simulation to assess surgical change virtually and final occlusion enabling user
to order copper NiTi wires to be placed the day before surgery.
Additionally, the posterior occlusal changes that occur with all
maxillary rotation surgeries could be assessed virtually. The final occlu-
Sion is planned from this simulation along with proper anterior palatal
root torque and posterior vertical positioning (two measures that prior to
3D technology could not be evaluated accurately). With virtual wire plan-
ning, I could create final copper NiTi arch wires that were placed the day
before surgery. Ideal shape memory wires now could be guiding active
tooth movement to final tooth positions immediately post-surgery when
RAP is occurring (Fig. 12).






275
SureSmile": A Clinical Perspective
2D/3D cant Alignment Max, Mand, Alignment
X-ray Lateral Ceph-220/2006 Translation ſmm) Rotation [deg.
- º 'º º żº º º
Horizontal Indination. - - *: |- post (-) º =sº sº º --
Anterior posterior; 19.9° — º - º - º, —º. - º
Right/Left: L. 9.0° L - 20 - 20 - 59 - º
- - 1 - 27 - 23 - - -
ºceph wiew Euse common rotation axis Dusecondyle axis []sync.uſ
[]chewsimulation |Malocclusion Indudes Max, Mand, Alignment adjustments Reset
Figure 11. SureSmile" virtual planning software showing the final oc-
clusion of the same patient in Figure 10.
Figure 12. Screenshots from SureSmile" software showing how sureSmile"
Wires may help to capitalize on the mechanical properties of copper NiTi during
Rapid Acceleratory Phenomenon (RAP) immediately post-surgery.



276
Snyder
Six weeks following differential maxillary impaction, the patient
was scheduled for removal of braces (Fig. 13). Figure 14 shows one-year
post-braces removal continued settling posteriorly.
SUMMARY
As an early user of SureSmile" technology, I have dedicated sig-
nificant amounts of time, effort and money to implement this powerful
clinical tool into my practice. Over the past eight years, I have ap-
proached this technology from three different outcome fronts: quality,
efficiency and cost. Professionally, I am compelled to look into these
three fronts independent of SureSmile". In this chapter I have attempted
to describe my in-depth experience of advancements and contributions
made by SureSmile" technology, measured clinical outcomes, clinical
-
Figure 13. Post-treatment photos. Patient was in braces a total of 13 months in-
cluding five months in SureSmile” wires.


277
SureSmile": A Clinical Perspective
Figure 14. Comparison of pre-scanning, post-treatment and one-year post-
treatment photos.
leveraging of targeted shape memory alloy wires made possible with 3D
virtual planning and finally, reasons for my changing utilization trends.
REFERENCES
Alford TJ, Roberts WE, Hartsfield JK, Eckert G.J. Snyder R.J. Clinical
outcomes for patients finished with the SureSmile" method compared
with conventional fixed orthodontics therapy. Angle Orthod 2011:
81:383–388.
American Board of Orthodontics. Grading system for dental casts and
radiographs. June 2008.
Cohen G, Campbell PM, Rossouw PE, Buschang PH. Effect of increased
Surgical trauma on rates of tooth movement and apical root resorption
in foxhound dogs. Orthod Craniofacial Res 2010:13:179–190.
Deguchi T, Honjo T, Fukunaga T, Miyawaki S, Roberts WE, Takano-
Yamamoto T. Clinical assessment of orthodontic outcomes with the
peer assessment rating, discrepancy index, objective grading System,
and comprehensive clinical assessment. Am J Orthod Dentofacial Or-
thop 2005; 127:434–443.

278
Snyder
Saxe AK, Louie LJ, Mah J. Efficiency and effectiveness of SureSmile".
World J Orthod 2010; 11:16-22.
Snyder R.J. Application of computer-assisted archwire fabrication in a
private practice setting. In: McNamara JA Jr, Kapila SD. Digital Ra-
diography and Three-Dimensional Imaging. Monograph 43, Cranio-
facial Growth Series, Department of Orthodontics and Pediatric Den-
tistry and Center for Human Growth and Development, The Univer-
sity of Michigan, Ann Arbor, 2006; 181-197.
Vu CQ, Roberts WE, Hartsfield JK Jr, Ofner S. Treatment complexity
index for assessing the relationship of treatment duration and out-
comes in a graduate orthodontic clinic. Am J Orthod Dentofacial Or-
thop 2008; 133:e 13-e 19.
Wilcko WM, Wilcko T, Bouquot JE, Ferguson DJ. Rapid orthodontics
with alveolar reshaping: Two case reports of decrowding. Int J Perio-
dont Rest Dent 2001:21:9-19.
279
280
USING FACIAL LASER SCANNING FOR
ASSESSING FACIAL SYMMETRY:
A PROSPECTIVE STUDY IN CHILDREN
AFFECTED BY CROSSBITE
Jasmina Primožić, Tiziano Baccetti,
Lorenzo Franchi, Maja Ovsenik
ABSTRACT
Facial asymmetry is defined as imbalance between the two sides of the face
(hemifaces). Although no human face is perfectly symmetrical, it is difficult to
distinguish normal asymmetries from small pathologic asymmetries associated
with malocclusions as unilateral posterior crossbite that already are present in
the primary dentition. The aim of this longitudinal study was to assess whether
correction of unilateral posterior crossbite in the primary dentition results in
improvement of facial symmetry. A group of 60 Caucasian children in the pri-
mary dentition, aged 5.3 + 0.7 years, were collected at baseline. The group con-
sisted of 30 children with a unilateral posterior crossbite with midline deviation
of at least 2 mm (XB) and 30 without malocclusion (NXB). The XB group was
treated using an acrylic plate expander. The children’s faces were scanned using
a three-dimensional (3D) laser-scanning device. Non-parametric tests were used
for data analysis to assess differences over the 30-month period of follow-up.
The XB children had statistically significantly greater facial asymmetry in the
lower part of the face (p<0.05) than the NXB children at baseline. There were
no statistically significant differences between the two groups at 6, 12, 18 and
30 months of follow-up. Treatment of unilateral posterior crossbite in the pri-
mary dentition period resulted in an improvement of facial symmetry in the
lower part of the face (p < 0.05). Treatment of unilateral posterior crossbite in
the primary dentition improves facial symmetry, though it creates normal condi-
tions for normal skeletal growth. The use of a 3D laser-scanning device helped
us to assess facial asymmetry more objectively.
KEY WORDS: asymmetry, three-dimensional, laser scanning, crossbite, early
treatment
281
Assessing Facial Symmetry
INTRODUCTION
Facial Symmetry
Symmetry and balance refer to the state of facial equilibrium, the
correspondence in size, shape and arrangement of facial features on op-
posite sides of the median sagittal plane, while asymmetry means imbal-
ance (Ercan et al., 2008). However, as no human face is perfectly sym-
metric, minor, nonpathologic facial asymmetry or, normal asymmetry is
relatively common (Burke, 1971; Shah and Joshi, 1978).
Several studies of normal asymmetry have reported that the right
hemiface is wider than the left one (Shah and Joshi, 1978; Farkas and
Cheung, 1981; Peck et al., 1991), some have found the left hemiface to
be wider (Burke, 1971; Vig and Hewitt, 1975; Pirttiniemi, 1994; Haragu-
chi et al., 2002), while others report no significant difference between the
right and left hemiface size (Bishara et al., 1994).
On the other hand, pathologic facial asymmetry has been associ-
ated with congenital anomalies such as cleft lip and hemifacial mi-
crosomia, syndromes of the head and neck, childhood fracture of the jaw
and unilateral posterior crossbite (Pirttiniemi et al., 1989; Bishara et al.,
1994; Pirttiniemi, 1994; McCance et al., 1997; Primožić et al., 2009).
Assessment of Facial Asymmetry
Several direct and indirect methods can be performed in order to
evaluate facial asymmetry (Ercan et al., 2008), including the use of direct
measurements on the face or assessment of facial asymmetry on photo-
graphs or posteroanterior (PA) cephalograms of the head.
Although face photography is an important diagnostic tool in or-
thodontics (Ferris, 1927), its main disadvantage is that it represents a
three-dimensional (3D) subject in two dimensions (2D; Robertson, 1976;
Moss et al., 1994).
Small deviations in camera angulations can give the illusion of
improving or worsening the facial images produced. If such images were
used to obtain measurements, the results would be inaccurate (Miller et
al., 2007). Along with photographs, the traditional method to assess fa-
cial symmetry is to use frontal radiographs. For evaluation of transverse
skeletal discrepancies, the PA cephalogram is the most readily available
and reliable diagnostic tool. However, the use of PA cephalograms still is
questionable for small children due to radiographic exposure (Allen et
al., 2003).
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Primožić et al.
On frontal photographs and PA radiographs assessment of facial
asymmetry performed by comparing morphometric measurements such
as distances, areas, angles and ratios of the left and right sides (Burke
and Healy, 1993: Shaner et al., 2000; Ferrario, 2001; Baudouin and Ti-
berghien, 2004). Such methods, however, provide information that refers
only to local imbalances; they do not allow full facial analysis and are
not able to reveal shape differences between the two sides (Ferrario et
al., 1993, 1995). Further, assessment of facial asymmetry on both, pho-
tographs and PA radiographs, imply a 2D assessment of a 3D facial
change that provides incomplete data and does not account for differ-
ences in facial depth and shape (Moss et al., 1994; Da Silveira et al.,
2003). The main disadvantage of evaluating facial asymmetry with any
of these methods also is that the criteria for determining the facial mid-
line need to be defined, despite the fact that it has been reported that
there is no absolute facial midline (Haraguchi et al., 2008).
Statistical shape analysis was developed to compare body forms
by using specific landmarks determined by anatomical prominences
(Lele and Richtsmeier, 1991; Ferrario et al., 1995; Hennessy et al., 2004,
2006; Mutsvangwa and Douglas, 2007). Several procedures for obtaining
such shape information from anatomical landmark data have been pro-
posed. However, it has been reported that the use of landmarks increases
the degree of bias (Houston, 1983).
Recently, several methods of analyzing facial changes in 3D
have been developed (Moss et al., 1987; Ferrario et al., 1994; Hell, 1995;
Hajeer et al., 2004; Kau et al., 2005), including surface laser scanning.
The laser scanner can be used as a soft tissue scanner and is a valuable
tool for its ease of application and creation of 3D images. Images have
been created to establish databases for normative populations (Yamada et
al., 2002), cross-sectional growth changes (Nute and Moss, 2000) and
also to assess clinical outcomes in surgical (Moss et al., 1988; McCance
et al., 1992, 1997; Ayoub et al., 1998) and non-surgical treatments
(McDonagh et al., 2001; Ismail et al., 2002; Moss et al., 2003; Primožić
et al., 2009) in the head and neck regions.
Facial Asymmetry in Patients Affected by Crossbite
Unilateral posterior crossbite is an anomaly that develops as a re-
sult of asymmetrical dental and/or skeletal development. In the primary
dentition, unilateral crossbite commonly arises as a result of a narrow
maxilla that may be a result of genetic or environmental influences, or
typically a combination of both. Unilateral functional crossbite often
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Assessing Facial Symmetry
manifests as a discrepancy between the upper and lower dental midlines
(centrelines) that also may be associated with facial asymmetry (Allen et
al., 2003).
Functional asymmetry in unilateral posterior crossbite can con-
tribute to mandibular skeletal asymmetry as during the growth period
continuous condylar displacement in the glenoid fossa induces differen-
tial growth of the condyles (Inui et al., 1999; Kilic, 2008). This asym-
metrical function reflects different development of the elevator muscles
on each side of the jaws leading to a thinner masseter muscle on the
crossbite side, which already is seen in the early mixed dentition (Kil-
iaridis et al., 2003). Further, the level of maximum bite force in children
with unilateral posterior crossbite is smaller compared to children with
neutral occlusion (Sonnensen et al., 2001). Early corrections of func-
tional problems should prevent adverse dental and facial development
(Ninou and Stephens, 1994; Proffit, 2006; Ovsenik, 2009).
Facial asymmetry due to lateral mandibular displacement in uni-
lateral posterior crossbite, if not treated in the primary dentition, may
lead to an undesirable growth modification (Ninou and Stephens, 1994;
Kilic, 2008), which results in facial asymmetry of skeletal origin. There-
fore, early orthodontic treatment seems to be desirable and beneficial to
create conditions for normal dental and skeletal development (Petren et
al., 2003).
Need for Treatment of Unilateral Posterior Crossbite and Assessment of
Treatment Outcome in the Primary Dentition Period
Preventive and early treatment in orthodontics still is the subject
of continuous debate and controversy regarding cost effectiveness in
analysis of functional and psychosocial benefit (Tschill et al., 1997; Prof-
fit, 2006; Ovsenik et al., 2007). A condition that typifies this controversy
is the treatment of a posterior crossbite in the primary dentition period
(Malandris and Mahoney, 2004).
Although a considerable number of studies investigating the ef-
fects of correcting posterior crossbites have been conducted, the out-
comes are different (Harrison and Ashby, 2001; Petren et al., 2003; Ma-
landris and Mahoney, 2004). It has been reported that relapse after early
crossbite correction is frequent (Kurol and Berglund, 1992), while other
studies report a success rate of 85% over an eight year follow-up (de
Boer and Steenks, 1997).
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Primožić et al.
It has been shown previously that correcting unilateral posterior
crossbite by maxillary expansion in children eliminates skeletal and den-
tal asymmetries (Hesse et al., 1997; Pinto et al., 2001).
Treatment success after correction of unilateral posterior cross-
bite in the primary dentition is highly questionable as it is difficult to as-
sess objectively the correction of facial asymmetry in small growing
children. The purpose of this study was to establish a new approach to
diagnosis and evaluation of treatment outcomes of unilateral posterior
crossbite in the primary dentition.
SUBJECTS AND METHODS
A group of 60 Caucasian children, aged 3.4 to 6.7 years (mean
5.3 + 0.7 years), were included in this study. The NXB group consisted
of 30 children (13 boys and 17 girls) without malocclusion, randomly
selected from a local kindergarten. In the XB group there were 30 chil-
dren (17 girls and 13 boys) with unilateral posterior crossbite. Only the
children in the primary dentition period with all the posterior teeth in
crossbite on one side and a midline deviation of at least 2 mm, due to a
functional mandibular shift, were included. The functional mandibular
shift was assessed clinically by an experienced orthodontist. Nineteen
children had a functional shift on the right side, eleven on the left side.
Further, type of respiration, deglutition, tongue position, chewing pattern
and deleterious oral habits were recorded and reported elsewhere
(Melink et al., 2010; Sever et al., 2010; Volk et al., 2010).
The XB group was treated using an acrylic plate with a midline
screw to expand the maxillary arch. The acrylic plate with an anterior
bite plane was cemented on the upper primary molars. The screw was
activated 0.25 mm every two days for four weeks and an over-expansion
of the upper jaw was performed in all the patients. The plate was left in
place for four more weeks without activation. The acrylic plate was re-
moved and then was used as a removable retainer for four months. The
typical expansion in XB subjects was approximately 3.5 mm.
Laser facial scanning was performed at baseline and at 6, 18 and
30 month follow-ups in both XB and NXB groups. Surface facial images
were obtained using two Konica/Minolta Vivid 910 laser scanners angled
to capture left and right sides of the face with significant overlap in the
anterior part of the face to facilitate registration and merging of the two
images to produce one facial shell (Kau et al., 2004). By passing through
a cylindrical lens, the red laser beam produced by the emitter of the cam-
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Assessing Facial Symmetry
era was transformed into a horizontal plane/stripe of laser light. The laser
light plane/stripe was projected onto the object being scanned and was
swept vertically, from top to bottom, over its entire visible surface by
using a high precision internal galvanometric mirror. The charged couple
device (CCD) camera received the reflecting light from the object
through a light-receiving lens. Range data were calculated for the array
of digitized points on each profile by triangulation as the charged couple
device camera was fixed within the scanner head at an offset distance
and angle from the laser emitter (Fig. 1). Each point then was represented
by x, y and z coordinates.
receiving optical system
Figure 1. Triangulation principle.
These Konica/Minolta Vivid 910 laser scanners are eye safe and
have scanning time of about 2.5 seconds with a reported manufacturing
accuracy of 0.3 mm (http://www.konicaminolta.com). Natural head pos-
ture (NHP) was adopted as it has been shown to be reproducible clini-
cally (Kau et al., 2005). The technique for positioning the patient and
image capture has been validated and described elsewhere (Kau et al., 2004).
The 3D data were imported to a reverse modeling software pack-
age, Rapidform" 2006 (INUS Technology Inc., Seoul, Korea). Each Scan
of the face (left and right images) was processed in order to remove un-
wanted data, registered and merged to produce a complete facial image
(Fig.2). The facial shell was aligned to two planes: the midsagittal plane





286
Primožić et al.
original shell mirrored shell
overlap
Figure 2. Assessment of facial asymmetry. The original shell (dark red) is
flipped horizontally to obtain a mirrored shell (white). The original and mirrored
shells are overlapped and divided into three parts and a color deviation map of
differences between the two shells is generated (black color = shell-shell devia-
tions within 0.5 mm that we considered symmetric; red color = the positive,
while blue color = the negative differences) and a histogram showing the per-
centage of overlapping of the two shells.
(Y-Z) and the inner cantus of the eyes (X-Z). To check for left/right
symmetry, the original facial shell was flipped horizontally in order to
obtain the mirrored facial shell and the original and mirrored facial shells
were superimposed (Fig. 2). The facial shells were divided into three
parts: the upper part was defined as the part of the face above the inner
cantus plane; the middle part ranged from the inner cantus plane to the plane




287
Assessing Facial Symmetry
through the outer commissures of the lips; and the lower part was below
this plane (Fig. 2). The shell-to-shell deviations of the mirrored images
were recorded in terms of average shell-to-shell distance. Further, a color
deviation map was generated to show shell-to-shell deviations of the mir-
rored images (Fig. 2) and the percentage of mirrored shells overlapping
within 0.5 mm was recorded. Facial asymmetry was evaluated in terms
of average shell-to-shell distance and shells overlapping within 0.5 mm.
The larger the average distance and the smaller the percentage of over-
lapping, the greater is the facial asymmetry.
Statistical Analysis
The Statistical Package for Social Sciences Software release 13.0
(SPSS Inc., Chicago, IL) was used for data analysis. The balancing of
experimental groups by age and sex was tested with a Student t-test and a
Fisher exact test, respectively. After testing the normality of the data
with the Shapiro-Wilk test and Q-Q normality plots, and the equality of
variance among the datasets using Levene test, non-parametric methods
were used for data analysis.
Friedman test was used to assess the significance of the differ-
ences in every facial symmetry parameter (average distance and overlap-
ping) over the time points within each group. When significant interac-
tions were seen, a Bonferroni-corrected Wilcoxon test was used for
pairwise comparisons. A Mann-Whitney U-test was used to assess the
significance of the differences in every parameter between the two
groups within each time point. The facial symmetry parameters were
analyzed for the whole face as well as for the upper, middle and lower
parts of the face separately.
RESULTS
The results for the facial symmetry parameters of the whole face
and the upper, middle and lower parts of the face separately are shown in
Table 1 (average distances) and Table 2 (percentages of overlapping).
Longitudinally, no significant differences of the recorded parameters
were seen in the NXB group. On the contrary, in the XB group, signifi-
cant increases were observed in both the average distance of the upper
part of face and in the overlapping of the lower part of the face (p<0.05).
288
Primožić et al.
Table 1. The average distance between the original and mirrored facial shell in
the experimental groups over time and for the whole face and each part of the
face separately. Diff. = significance of the difference over time point or between
the groups: XB = crossbite; NXB = non-crossbite; * = statistically significantly
different as compared to the corresponding baseline value.

Part Time point
Parameter of Group 30 Diff.
the Baseline 6 months 18 months
face months
().44 + ().48 + ().44 + 0.44 +
Whole | NXB (). || (). 15 (). 12 ().08 NS
Average
distance ().5() + ().57 -- 0.45 + ().47 --
(mm) XB (). I 5 (). 19 (). 15 (). 12, NS
Diff. NS NS NS NS
().39 + 0.46 + 0.41 + 0.41 +
Upper | NXB (). I () 0.14 (). 13 0.08 NS
XB 0.42 + 0.48 + 0.40 + 0.45 + p <
(). () (). 15 + 0.15 (). 12 0.05
Diff. NS NS NS NS
g 0.43 + 0.45 + 0.44 + 0.45 +
Middle | NXB 0.16 0.17 0.13 0.12 NS
0.5 ! -- 0.53 + 0.42 + 0.47+
XB 0.22 0.26 0.15 0.16 || NS
Diff. NS NS NS NS
0.53 + O.64 + 0.48 + 0.45 +
Lower | NXB 0.24 0.48 0.26 0.14 | NS
0.67 + 0.77 == 0.61 + 0.52 +
XB 0.36 0.45 0.49 0.20 NS
Diff. NS NS NS NS
In particular, at the corresponding pairwise comparisons, the overlapping
recorded at 18 months was greater significantly as compared to the base-
line value. The comparisons between the two groups within each time
point for every parameter were not significant, with the exception for the
overlapping of the lower part of the face, which was significantly lower
in the XB group as compared to the NXB group at baseline (p<0.05).
289
Assessing Facial Symmetry
Table 2. The percentage of overlapping between the original and mirrored facial
shell in the experimental groups over time and for the whole face and each part
of the face separately. Diff. = significance of the difference over time point or
between the groups; XB = crossbite; NXB = non-crossbite; * = statistically sig-
nificantly different as compared to the corresponding baseline value.
Part Time point
Para-
meter of the Group Base- 30
face line 6 months 18 months months
Whole 69.27+ | 66.48 + 68.00 + 67.82 +
Over- 10.16 10.51 10.90 7.80
lapping 63.33 + 59.88 + 69.01 + 65.24 +
(%) 11.23 12.87 10.59 9.90
NS NS NS NS
72.85 + | 68.08 + 72.31 +
10.88 11.22 . 12.45
70.85 + || 65.13 + 72.71 +
8.70 12.21 12.39
NS NS NS
69.66 + 66.03 +
Middle 14.05 14.14
- 61.80 + 69.32 +
16.54 14.08
NS NS
61.80 + 65.35 +
17.85 21.22
50.70 + 64.81 +
24.12 16.93 +
p < 0.05 NS NS
DISCUSSION
Treatment success after correction of unilateral posterior cross-
bite in the primary dentition is questionable. It is difficult to assess objec-
tively correction of facial asymmetry in small children. As 3D laser
Scanning is a non-invasive and accurate method for assessing soft tissue
discrepancy (Kau et al., 2005, 2007), it can be used in the primary denti-
tion period.
3D soft tissue analysis for symmetry can be used easily in order
to determine treatment need in the primary dentition as well as to assess
treatment success and follow-up of the patients. Facial asymmetry can be
assessed without using reference points or planes, which previously has

290
Primožić et al.
been reported to be a more accurate method for assessing asymmetry
(Pirttiniemi et al., 1996). Further, asymmetry can be evaluated qualita-
tively by contemplating the color deviation map. Areas of greater asym-
metry and deviation can be assessed. Further, the asymmetry also can be
evaluated quantitatively in terms of average distance or by the percentage
of symmetry. The whole face or a part of it can be examined separately.
Therefore, 3D facial analysis makes diagnosis of XB and evaluation of
treatment outcome more objective and accurate. As there are no standard
norms that define normal asymmetry and pathologic asymmetry, the XB
children should be compared with a control group of children with no
malocclusion and no clinically detectable face asymmetries.
It has been reported that in unilateral posterior crossbite in the
primary dentition, facial asymmetry is a consequence of a lateral man-
dibular displacement, resulting in a deviation of the chin toward the
crossbite side (Malandris and Mahoney, 2004). The greatest facial
asymmetry of crossbite children was seen in the lower part of the face at
baseline and it was greater significantly compared to children without
malocclusion, which is in accordance with previous studies (Primožić et
al., 2009). The facial asymmetry of the lower part of the XB children
likely was a result of the functional mandibular shift that was present in
all of these children at baseline.
After treatment and at follow-ups, the asymmetry of the lower
part of the face in the XB children decreased and was not different sig-
nificantly from the NXB children. Further, the pattern of mastication of
the XB children included in this study was examined before and after
treatment and reported elsewhere (Sever et al., 2010). These authors re-
ported that the children with crossbite had a significantly different pat-
tern of mastication compared to the non-crossbite children. After treat-
ment, the pattern of mastication changed and was not different signifi-
cantly from the pattern of the non-crossbite children (Sever et al., 2010).
Treatment of the unilateral posterior crossbite with an expansion plate
has influence on the position of the mandible in centric occlusion and it
corrects facial asymmetry in the lower part of the face.
CONCLUSION
The laser scanner can be used as a soft tissue scanner and has
proved to be a valuable tool for its ease of application and creation of 3D
images. This technology should become a routine diagnostic tool in pe-
diatric and orthodontic practice. Further, assessment of facial asymmetry
291
Assessing Facial Symmetry
on 3D images is a valid method for assessing treatment outcome after
correction of unilateral posterior crossbite in the primary dentition.
REFERENCES
Allen D, Rebellato J, Sheats R. Ceron AM. Skeletal and dental contribu-
tions to posterior crossbites. Angle Orthod 2003;73:515-524.
Ayoub AF, Siebert P, Moos KF, Wray D, Urquhart C, Niblett TB. A vi-
sion-based three-dimensional capture system for maxillofacial as-
sessment and surgical planning. Br J Oral Maxillofac Surg 1998:36:
353–357.
Baudouin JY, Tiberghien G. Symmetry, averageness and feature size in
the facial attractiveness of women. Acta Psychol (Amst) 2004; 1 17:
3.13-332.
Bishara SE, Burkey PS, Kharouf JG. Dental and facial asymmetries: A
review. Angle Orthod 1994;64:89–98.
Burke PH. Stereophotogrammetric measurement of normal facial asym-
metry in children. Hum Biol 1971;43:536-548.
Burke PH, Healy MJ. A serial study of normal facial asymmetry in
monozygotic twins. Ann Hum Biol 1993:20:527–534.
Da Silveira AC, Daw JL Jr, Kusnoto B, Evans C, Cohen M. Craniofacial
applications of three-dimensional laser surface scanning. J Craniofac
Surg 2003; 14:449-456.
de Boer M, Steenks MH. Functional unilateral posterior crossbite: Or-
thodontic and functional aspects. J Oral Rehabil 1997:24:614-623.
Ercan I, Ozdemir ST, Etoz A, Sigirli D, Tubbs RS, Loukas M, Guney I.
Facial asymmetry in young healthy subjects evaluated by statistical
shape analysis. J Anat 2008;213:663-669.
Farkas LG, Cheung G. Facial asymmetry in healthy North American
Caucasians: An anthropometrical study. Angle Orthod 1981;51:70-
77.
Ferrario VF, Sforza C, Ciusa V, Dellavia C, Tartaglia GM. The effect of
sex and age on facial asymmetry in healthy subjects: A cross-
sectional study from adolescence to mid-adulthood. J Oral Maxillofac
Surg 2001:59:382–388. -
Ferrario VF, Sforza C, Miani A Jr, Serrao G. A three-dimensional
evaluation of human facial asymmetry. J Anat 1995;186:103-110.
292
Primožić et al.
Ferrario V, Sforza C, Miani A, Tartaglia G. Craniofacial morphometry
by photographic evaluations. Am J Orthod Dentofacial Orthop 1993;
| 03:327–337.
Ferrario VF, Sforza C, Poggio CE, Tartaglia G. Distance from symmetry:
A three-dimensional evaluation of facial asymmetry. J Oral Maxillo-
fac Surg 1994:52: 1126–1132.
Ferris HC. Original photographic studies of orthodontic cases. Int J Or-
thodont Oral Surg 1927; 13:627-637.
Hajeer MY, Millett DT, Ayoub AF, Siebert J.P. Applications of 3D imag-
ing in orthodontics: Part I. J Orthod 2004:31:62-70.
Haraguchi S, Iguchi Y, Takada K. Asymmetry of the face in orthodontic
patients. The Angle Orthodontist 2008;78:421-426.
Haraguchi S, Takada K, Yasuda Y. Facial asymmetry in subjects with
skeletal Class III deformity. Angle Orthod 2002:72:28-35.
Harrison JE, Ashby D. Orthodontic treatment for posterior crossbites.
Cochrane Database of Systematic Reviews 2001, Issue 1. Art. No.:
CD000.979. DOI: 10.1002/1465,1858. CD000979.
Hell B. 3D sonography. Int J Oral Maxillofac Surg 1995:24:84–89.
Hennessy RJ, Lane A, Kinsella A, Larkin C, O’Callaghan E, Wadding-
ton JL. 3D morphometrics of craniofacial dysmorphology reveals sex-
specific asymmetries in schizophrenia. Schizophr Res 2004;672:261-
268.
Henessy RJ, McLearie S, Kinsella A, Waddington JL. Facial shape and
asymmetry by three-dimensional laser surface scanning covary with
cognition in a sexually dimorphic manner. J Neuropsychiatry Clin
Neurosci 2006; 18:73–80.
Hesse KL, Artun J, Joondeph DR, Kennedy DB. Changes in condylar
position and occlusion associated with maxillary expansion for cor-
rection of functional unilateral posterior crossbite. Am J Orthod Den-
tofacial Orthop 1997;1 11:410-418.
Houston WJ. The analysis of errors in orthodontic measurements. Am J
Orthod 1983;83:382–390.
Inui M, Fushima K, Sato S. Facial asymmetry in temporomandibular
joint disorders. J Oral Rehabil 1999:26:402-406.
Ismail SF, Moss JP, Hennessy R. Three dimensional assessment of the
effects of extraction and nonextraction orthodontic treatment on the
face. Am J Orthod Dentofacial Orthop 2002;121:244-256.
293
Assessing Facial Symmetry
Kau CH, Hunter LM, Hingston E.J. A different look: 3-dimensional facial
imaging of a child with Binder syndrome. Am J Orthod Dentofacial
Orthop 2007;132:704–709.
Kau C, Richmond S, Zhurov A, Knox J, Chestnutt I, Hartles F, Playle R.
Reliability of measuring facial morphology with a 3-dimensional laser
scanning system. Am J Orthod Dentofacial Orthop 2005; 128:424-430.
Kau CH, Zhurov A, Scheer R, Bouwman S, Richmond S. The feasibility
of measuring three-dimensional facial morphology in children. Or-
thod Craniofac Res 2004;7: 198-204.
Kiliaridis S, Georgiakaki I, Katsaros C. Masseter muscle thickness and
maxillary dental arch width. Eur J Orthod 2003:25:259-263.
Kilic N, Kiki A, Oktay H. Condylar asymmetry in unilateral posterior
crossbite patients. Am J Orthod Dentofacial Orthop 2008;133:382–387.
Kurol J, Berglund L. Longitudinal study and cost-benefit analysis of the
effect of early treatment of posterior cross-bites in the primary denti-
tion. Eur J Orthod 1992; 14:173-179.
Lele S, Richtsmeier JT. Euclidean distance matrix analysis: A coordi-
nate-free approach for comparing biological shapes using landmark
data. Am J Phys Anthropol 1991;86:415-427.
Malandris M, Mahoney EK. Aetiology, diagnosis and treatment of poste-
rior cross-bites in the primary dentition. Int J Paediatr Dent 2004;
14:155–166.
McCance AM, Moss JP, Fright WR, James DR, Linney AD. A three-
dimensional analysis of soft and hard tissue changes following bimax-
illary orthognathic surgery in skeletal III patients. Br J Oral Maxillo-
fac Surg 1992:30:305-312.
McCance AM, Moss JP, Fright WR, Linney AD, James DR. Three-
dimensional analysis techniques: Part 1. Three dimensional soft-tissue
analysis of 24 cleft palate patients following LeFort I maxillary ad-
vancement: A preliminary report. Cleft Palate Craniofac J 1997:34:
36-45.
McDonagh S, Moss JP, Goodwin P, Lee RT. A prospective optical sur-
face scanning and cephalometric assessment of the effect of func-
tional applicances on the soft tissues. Eur J Orthod 2001:23:115-126.
Melink S, Vagner MV, Hocevar-Boltezar I, Ovsenik M. Posterior cross-
bite in the deciduous dentition period, its relation with sucking habits,
irregular orofacial functions, and otolaryngological findings. Am J
Orthod Dentofacial Orthop 2010;138:32-40.
294
Primožić et al.
Miller L, Morris DO, Berry E. Visualizing three-dimensional facial soft
tissue changes following orthognathic surgery. Eur J Orthod 2007:29:
14–20.
Moss JP, Grindrod SR, Linney AD, Arridge SR, James D. A computer
system for the interactive planning and prediction of maxillofacial
surgery. Am J Orthod Dentofacial Orthop 1988;94:469-475.
Moss JP, Ismail SF, Hennessy R.J. Three-dimensional assessment of
treatment outcomes on the face. Orthod Craniofac Res 2003;6 S1:
126-13 1.
Moss JP, Linney AD, Grindrod SR, Arridge SR, Clifton JS. Three-
dimensional visualization of the face and skull using computerized
tomography and laser scanning techniques. Eur J Orthod 1987;9:247-253.
Moss JP, McCance AM, Fright WR, Linney AD, James DR. A three-
dimensional soft tissue analysis of fifteen patients with Class II, Divi-
sion 1 malocclusions after bimaxillary surgery. Am J Orthod Dento-
facial Orthop 1994; 105:430-437.
Mutsvangwa T, Douglas TS. Morphometric analysis of facial landmark
data to characterize the facial phenotype associated with fetal alcohol
syndrome. J Anat 2007:210:209–220.
Ninou S, Stephens C. The early treatment of posterior crossbites: A re-
view of continuing controversies. Dent Update 1994:21:420-426.
Nute SJ, Moss JP. Three-dimensional facial growth studied by optical
surface scanning. J Orthod 2000:27:31-38.
Ovsenik M. Incorrect orofacial functions until 5 years of age and their
association with posterior crossbite. Am J Orthod Dentofacial Orthop
2009;136:375-381.
Ovsenik M, Farcnik FM, Korpar M, Verdenik I. Follow-up study of
functional and morphological malocclusion trait changes from 3 to 12
years of age. Eur J Orthod 2007:29:523-529.
Peck S, Peck L, Kataja M. Skeletal asymmetry in esthetically pleasing
faces. Angle Orthod 1991;61:43-48.
Petren S, Bondemark L, Soderfeldt B. A systematic review concerning
early orthodontic treatment of unilateral posterior crossbite. Angle
Orthod 2003;73:588-596.
Pinto AS, Buschang PH, Throckmorton GS, Chen P. Morphological and
positional asymmetries of young children with functional unilateral
posterior crossbite. Am J Orthod Dentofacial Orthop 2001;120:513-
520.
295
Assessing Facial Symmetry
Pirttiniemi PM. Associations of mandibular and facial asymmetries: A
review. Am J Orthod Dentofacial Orthop 1994:106:191-200.
Pirttiniemi P, Lahtela P, Huggare J, Serlo W. Head posture and dentofa-
cial asymmetries in surgically treated muscular torticollis patients.
Acta Odontol Scand 1989:47: 193-197.
Pirttiniemi P., Miettinen J, Kantomaa T. Combined effects of errors in
frontal-view asymmetry diagnosis. Eur J Orthod 1996; 18:629–636.
Primožič J, Ovsenik M, Richmond S, Kau CH, Zhurov A. Early crossbite
correction: A three-dimensional evaluation. Eur J Orthod 2009:31:
352-256.
Proffit WR. The timing of early treatment: An overview. Am J Orthod
Dentofacial Orthop 2006;129:S47-S49.
Robertson NR. Contour photography. Br J Orthod 1976:3:105-109.
Sever E, Marion L, Ovsenik M. Relationship between masticatory cycle
morphology and unilateral crossbite in the primary dentition. Eur J
Orthod e-pub 2010 Nov 30, doi:10.1093/ejo/cjq070.
Shah SM, Joshi MR. An assessment of asymmetry in the normal cranio-
facial complex. Angle Orthod 1978;48:141-148.
Shaner DJ, Peterson AE, Beattie OB, Bamforth JS. Assessment of soft
tissue facial asymmetry in medically normal and syndrome-affected
individuals by analysis of landmarks and measurements. Am J Med
Genet 2000;93: 143-154.
Sonnesen L, Bakke M, Solow B. Bite force in pre-orthodontic children
with unilateral crossbite. Eur J Orthod 2001:23:741-749.
Tschill P, Bacon W, Sonko A. Malocclusion in the deciduous dentition
of Caucasian children. Eur J Orthod 1997; 19:361-367.
Vig PS, Hewitt AB. Asymmetry of the human facial skeleton. Angle Or-
thod 1975;45:125-129.
Volk J, Kadivec M, Music MM, Ovsenik M. Three-dimensional ultra-
sound diagnostics of tongue posture in children with unilateral poste-
rior crossbite. Am J Orthod Dentofacial Orthop 2010;138:608-612.
Yamada T, Mori Y, Minami K, Mishimi K, Tsukamoto Y. Three-
dimensional analysis of facial morphology in normal Japanese chil-
dren as control data for cleft surgery. Cleft Palate Craniofac J 2002;
39:517-526.
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THE AAOF CRANIOFACIAL GROWTH LEGACY
COLLECTION: A POWERFUL NEW TOOL FOR
ORTHODONTIC TEACHING AND RESEARCH
Sheldon Baumrind and Sean Curry
ABSTRACT
This chapter reports and illustrates a multi-institutional project that uses the ca-
pabilities of cloud computing and the Internet to collect and share craniofacial
images and numerical data of importance to orthodontic education and research.
The project will provide interested investigators all over the world with near-
instantaneous access to longitudinal information on the spontaneous craniofacial
growth of untreated children with various kinds of malocclusion. The collection
will facilitate investigations on the spontaneous course of development in chil-
dren with malocclusions of different types. In addition, the AAOF Legacy Col-
lection constitutes a unique source of control samples for testing the validity of
consensually accepted beliefs about the effects of orthodontic treatment.
KEY WORDS: cephalometrics, lateral headfilm, American Association of Ortho-
dontists Foundation, landmarks, normal growth
INTRODUCTION
With support from the American Association of Orthodontists
Foundation (AAOF), nine of the twelve known collections of longitudi-
nal craniofacial growth records in the United States (U.S.) and Canada
have joined together to create a website of cephalometric images with an
underlying numerical database. The first implementation of this joint
effort already is available for use by orthodontists everywhere with any
standard Internet browser. Its purpose is to make representative materials
from the participating collections readily available to clinicians, cranio-
facial investigators, students of craniofacial growth and interested mem-
bers of the public.
The participating collections represent the work of hundreds of
investigators. The materials they contain literally are irreplaceable. The
contents of the several collections include longitudinal skull x-ray im-
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AAOF Craniofacial Growth Legacy Collection
ages of various sorts – intraoral radiographs, study casts, hand-wrist
films and facial photographs, as well as written records charting the
physical and educational development of children of different ethnicities
and growth patterns.
These longitudinal records have been gathered, catalogued and
studied over more than 75 years. Each collection is independent from the
others and has pursued its own strategies of sampling and data collection.
The product of these different and complementary strategies constitutes a
rich longitudinal record of craniofacial development among children who
never received orthodontic treatment. The intent of the AAOF is to
gather representative subsets of records from all available collections and
to make the combined materials freely available to all interested clini-
cians and craniofacial investigators via the Internet.
HISTORY OF THE PROJECT
Scattered throughout the U.S. and Canada are a number of longi-
tudinal collections of x-ray images and other physical records of cranio-
facial development of growing children with normal occlusions and chil-
dren with malocclusions who did not receive orthodontic treatment. Most
of these collections are located at major universities. The longitudinal
records they contain were acquired during a historically brief window in
time roughly between 1930 and 1985.
Prior to 1930, the technological capacity for tracking and record-
ing the growth of the internal structures of the human head through time
did not exist. Yet well before the end of the 20th century, the continued
gathering of such information from untreated children was precluded by
the recognition of the possibility of deleterious effects from the excessive
use of ionizing radiation for diagnostic purposes. Clearly longitudinal
studies of this kind never can be repeated. It seems imperative, therefore,
that the available records be preserved in digital form before the deterio-
ration or loss of the original images makes that impossible.
t In 1988, out of concern for the preservation of this important re-
search legacy, The National Institute of Dental Research (NIDR) spon-
sored a survey of existing longitudinal records collections in the U.S. and
Canada by Hunter and associates (1993). Their report identified twelve
extant collections containing various combinations of x-ray cephalo-
grams, plaster study casts of the teeth, demographic documentation and
other physical records. Taken together, these collections have been the
source of a large portion of the available published information on longi-
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Baumrind and Curry
tudinal craniofacial growth, including more that 200 peer reviewed pa-
pers in major scientific journals.
The bibliography of this paper lists a subset of these publica-
tions, including four major dental and craniofacial atlases (Riolo et al.,
1974; Broadbent et al., 1975; Moyers et al., 1976; Behrents, 1985) and
representative papers from several collections (Lewis and Roche, 1977,
1988; McNamara, 1981; Ohtsuki et al., 1982; Lewis et al., 1985;
McNamara et al., 1985, 1990; Behrents, 1986; Baumrind et al., 1987a,b,
1992a, b, 1996; Korn and Baumrind, 1990; Baumrind and Korn, 1992;
Snodell et al., 1993; Formby et al., 1994; Nanda and Ghosh, 1995;
Blanchette et al., 1996; Hunter et al., 2002, 2007; Baccetti et al., 2005;
Hesby et al., 2006; Edwards et al., 2007; Gu and McNamara, 2007,
2009; Sherwood et al., 2011).
Many of these publications are required reading for orthodontic
and oral and maxillofacial surgery residents in the U.S. and elsewhere.
Some of them, particularly the three atlases, have contributed strongly to
the belief systems from which clinicians approach the delivery of ortho-
dontic and maxillofacial surgical treatment throughout the world. As
valuable as the data in these publications are, they represent only a small
portion of the irreplaceable information contained in the original images
in the several collections.
The idea of preserving a substantial subset of these irreplaceable
images and their associated numerical data in digital form had been a
dream of clinicians and craniofacial investigators for many years. Such a
merged collection, if organized systematically, would provide a major
resource for future orthodontic teaching and research. For this reason, it
seemed imperative that the original images in the collections be pre-
served in digital form as soon as possible in order to facilitate continued
examination and hypothesis-driven study by craniofacial investigators,
clinicians, physical anthropologists and other interested scholars.
In 2008, Mark Hans and his Case Western Reserve University
associates received support from the AAOF to organize a meeting of rep-
resentatives from a number of interested institutions to investigate the
potential for developing a shared virtual resource of longitudinal cranio-
facial growth records. This meeting led to the formation of a consortium
among the separate collections to test the feasibility of constructing a
sharable image base and database with continuing support from AAOF.
Nine of the twelve collections identified in the paper by Hunter
and colleagues (1993) collaborated in this consortium. The universities
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AAOF Craniofacial Growth Legacy Collection
and institutes involved include Case Western University, The University
of Michigan, The University of Iowa, The University of Oklahoma, The
Oregon Health and Science University, The University of the Pacific,
The University of Toronto, The Forsyth Institute and The Wright State
University-Fels Institute. In the early stages of the project, Leslie Will
(then at Tufts School of Dentistry) served as liaison between the AAOF
and the consortium and Carla Evans (at The University of Illinois Chi-
cago, School of Dentistry) provided a link to the American Association of
Orthodontists.
Stage I (the initial phase of the project) started in 2009 and was
designed specifically as a test of feasibility. The representatives of the
nine participating collections, meeting together, designated the Craniofa-
cial Research Instrumentation Laboratory (CRIL) at The University of
the Pacific as the site for the development of a prototype sharable data-
base and website to which each of the collections would contribute mate-
rials for a small sample of cases. The framework for this database and its
associated website was constructed using prototype components that had
been developed previously at CRIL with NIH support (1971-1990), cou-
pled with supplementary assistance from The University of the Pacific,
The University of California San Francisco, a Center grant from AAOF
and the family of the late Dr. J. Rodney Mathews.
Stage I lasted from June 2009 to December 2010. During this pe-
riod, the consortium successfully developed a functional craniofacial da-
tabase and website that demonstrated conclusively the feasibility of col-
laboration among our several independent collections. The status of the
website as of June 2011 (essentially as it looked at the end of stage I) is
illustrated in tables and figures that follow.
The home page of the AAOF Legacy Collection is shown in
Figure 1. It can be accessed on any Internet-capable device via any stan-
dard browser or directly at www.AAOFLegacyCollection.org. The in-
formation content of this page, and indeed of the rest of the website, is
packed rather densely. Even though we have sought to make the site at-
tractive, little attention has been given to making it look pretty. The left
hand column on the home page is a navigation bar, directing the user
through the major categories of the website and database holdings. The
uppermost category of the navigation bar directs the user to information
about the site itself (Fig. 2).
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Baumrind and Curry
AAOF craniofacial Growth Legacy Collection
welcome! - --
- Collection Highlights
------- with support from the American Association of orthodontists Foundation (anoº.
------ nine of the eleven known collections of longitudinal craniofacial growth records in
the United States and Canada have joined together to create this web site and its
underlying numerical database-out purpose is to make representative materials
-------- from the participating collections available for viewing and further investigation by
clinicians, craniofacial investigators, students of human growth, and interested
---------------------
ºri-º-º-º-
--- member-of-the-public.
-------
--- The-collection-represent-the-ork ºf hundreds of investigators. They have been
---. --tº-red-cataloged, and studied over-period of more than seventy-five-years.
--- The m-terial-they contain-º-º-º-º-º-c-b-Each of the collection--
independent from the others and has pursued its ownsampling and data collection
strateg-T-together-th-ºº-ºnd complementary strateg-h-
--- produced-rich longitudinal record of craniofacial development among children who
did not receive orthodont-tº-tment-available documentation of the growth
º- process in the several collection-includes sºul-ray images of various-art-hand-
--- wrist film-dental radiograph-facial photographs, and study casts as well-
------- º record-on-th-physical and educational development of children of varied
º- º ethnicº-and-growth pattern-
--- The contributing collection-working individually, have produced most of the
--- information that is -lable in the contemporary orthodontic uterature on
ºn tº longitudin-ºr-not-growth in untreated children-no-by merging data from
|-- th--ever-collection---hop-to-mak-possible further collaborative-tudies that
-enrich and refine our knowledge of craniofacial gro-thin untreated children and
----- ---------
-º-º-º-º-º-º:
D-G- During the initial phase of this project which is no-neering completion--have
-------- confined ourselves to the collection of lateral and frontal cephalograms.
available on the sit-ºr-digital images of 1530 lateral cephalograms generated at
------- differentages from 155 cases gathered from 9 different collections. -
B-Gº- statistics on case distribution by sex/gender, age and Angle-class may be found by
--- clicking on "collection statistics" in the Information section of the menu on the left
--- side of this page
---
Fºnt-
This entire site is intended to be viewed as a work in progress, intended to function
--- as a continually developing resource for orthodontic teaching and research. Its
----- primary role is to serve as a repository for longitudinal records of all types with
Mºnº sufficient numerical documentation to facilitate useful search and querying.
Dºnº
Getting Started
------------- --------- the collection Highlights box at the
-------------- --ºn-ºn - -
--------- escription of each collection. Then just cºck on
the collection name to get-more detailed description, plus-link to see the
-----------------------------------------------------
jump to the description page.
-ºcking on the "overvie-of-al-left menu item takes you to a page showing
Overviews of all the Collections, with links to each Collection's description and
records-cºcking on the collection name under the "Browse images" left menu
section takes you directly to the collection's records.
use of Materials from This site
In creating and sustaining this site. AAof and the participating cºllections seek to
make possible the widest use of its unique materials in education and research. To
that end, the entire content of the site is made available without cost-for-on-line use
and downloading by all members of the orthodontic community, other investigators
and members of the public may also request permission to download site materials
contingent upon agreement by the collection that was the original source of the
materials in question. The pixel resolution of the images on the site is considered
-----
origin directly, being aware that some the collections may find it necessary tº
charge for such higher resolution images.
when images obtained from this site are used in presentations ºr publications, the
AAof and the collection of origin should be cited appropriately.
Figure 1. The AAOF Legacy website home page (December 2010).
Tables 1 and 2 and Figure 3 summarize collection statistics at the
end of stage I. All nine collections were represented in the sample that
contained serial lateral cephalogram for 149 individual subjects. The to-
tal number of lateral cephalograms was 1285, of which searchable nu-
merical data had been encoded for 1168. Of the 149 cases, 93 were de-
scribed as Angle Class I, 44 as Angle Class II and 11 as Angle Class III.
There were 76 girls and 73 boys in the sample.

























































301
AAOF Craniofacial Growth Legacy Collection
AAOFE: **o-cranioteca Growth Legacy collection
| --- collection Highlight-
- ----------------
Info mation º- ------------
- ---------------
-º-º-º-º-º-º-º-º-º-º-º:
--------
- ----------- ---
About AAOF --- ------ --
--- --------- ------
- ----------------
------------
- - - - -----------------------
---------------
------ ---------------
-------------
--- ----- ----------
- ---------------------
Ontacts ----
- - - ----------
- -------------------
- - -- --- -----------
Collection Statistics -------------------
--- -------------
- ---
--------------
A. k I d - --------------
CKnowledgements - ------------------
- ------------------
---------------
--- ------------------------
- ---
-
-----------------
-- --- --- ---
- -----------------
--- -----
-- ---------
ºng
-- ------- --- ---
--- -------- ----- ---
--- ----- ------
- ------------- -----
--- -
--- ----------------------
--- ------------------
--- ---
Figure 2. Accessing information on the site via the navigation bar on the home page.
Table 1. Contents of the AAOF Legacy Collection website at the end of
stage I. * Lateral cephalograms only. Site also includes 472 PA (frontal)
cephalograms for 52 cases.
Number of collections represented 9
Number of cases 149
Total number of images” 1285
Total images searchable in database 11.68
Average number of images per case 8.6
Table 2. Frequencies by Angle class and sex.
Class I Class II | Class III | TOTALS
Female 48 24 4. 76
Male 46 20 7 73
TOTALS 94 44 11 149

302

Baumrind and Curry
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- - - - - -
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Figure 3. A. Number of available images (y) at each
age (x), all cases. B. Number of available images (y)
at each age (x), by sex. C. Number of available im-
ages (y) at each age (x) by Angle class.
Figure 3 illustrates the distribution of lateral cephalograms by
age and reflects the primary focus on the time interval between ages
seven and 20 years, the period of growth in which most orthodontic
treatment occurs. (This focus since has been extended downward to five
years of age in order to get a better sense of the conditions associated
with the eruption of the first permanent molar.) Figure 3A shows that
even in this early stage, the number of images available at each age be-
tween six and seventeen is greater than number of untreated control sub-
jects in almost all studies of orthodontic treatment outcome that have
been published to date.
303
AAOF Craniofacial Growth Legacy Collection
The distribution of images by sex (Fig. 3B) is matched surpris-
ingly evenly but the number of images for girls slightly exceeds that for
boys between the ages of eight and twelve while the number of images of
boys is slightly greater than that for girls that an earlier and later time
points; there is no obvious explanation for this variation. The distribution
of images by Angle class (Fig. 3C) shows the heavy concentration of
Class I cases and the relatively limited number of Class III cases. This
distribution is fairly representative of that in the normal population but
does not necessarily reflect the focus of interest among orthodontic clini-
cians who generally would prefer to have more information about the
spontaneous development of Class II and Class III malocclusions.
General information on the composition of the several collec-
tions from which the AAOF sample has been drawn may be found by
clicking on the links in the Browse Collections Descriptions section of
the navigation bar (Fig. 4). These descriptions highlight the features of
the individual collections and may be browsed by the reader at will.
Direct access to the images of the AAOF collection is possible
through the links in the lower area of the home page navigation bar (Fig.
5). Selecting an individual collection here will bring the viewer to a new
page on which the images from all cases of the chosen collection are or-
dered sequentially. Data for each case in the chosen collection then may
be examined in greater detail. For example, clicking on the Mathews
Growth entry in Figure 5 takes the viewer to the first case of a detailed
inventory of the available cases and images from the Mathews implant
study originally conducted at The University of California San Francisco
(Fig. 6). The special feature of this participating collection is that the
subjects had implants of the Björk type placed prior to the collection of
longitudinal records. It may be seen that records for this subject are
available at ten time points ranging from six years eleven months to six-
teen years one month.
The user now can select the lateral cephalogram from any avail-
able age or time point for this case. For example, if one selects the image
represented by the highlighted grey bar in Figure 6, a full-screen view of
the lateral cephalogram taken at age nine years seven months is pre-
sented (Fig. 7). Note the two rows of function buttons below the image in
this enlarged view. They represent links to additional information available
→ Figure 5. Accessing the images in the collection. (At present, the Meharry
Collection is not part of this project.)
304
Baumrind and Curry
rowse Collections
Descriptions
Overview of All
Bolton-Brush Growth
Burlington Growth
Denver Growth
Fels Longitudinal
Forsyth Twin
Iowa Growth
Mathews Growth
Meharry Growth
Michigan Growth
Oregon Growth
Figure 4. Browsing descriptive
collections.
Browse Images
Bolton-Brush Growth
Burlington Growth
Denver Growth
Fels Longitudinal
Forsyth Twin
Iowa Growth
Mathews Growth
Meharry Growth
Michigan Growth
Oregon Growth
--------
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---
º AOFE -o-craniofacial Growth Legacy collection
----------------
------
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------------------------
---
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--- --- ---
---------------------
--- ---
-
--- ----------- -
--------
---
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--------------------
Collection Highlights
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-
information on the individual component
Collection Highlight-















AAOF Craniofacial Growth Legacy Collection
| Detailed Collection Inventory| Condensed Collection Inventory
Collection: UOP Mathews Growth Study (33 Subjects) Collection Description
| Collapse All Timepoint Grids | Expand All Timepoint Grids [. selecºmageReques | Clear All | Requestimages for Selected Subjects. |
| Collapse/Expand This Timepoint Grid Number of Time points: 10
subject: 001 Select Subject L
Sex: Male DOB: 7/1950 Time Image Age Preview Image (click to see Full size)
| Angle class: class I Treatment:none Pºint Date
- - - -
Lateral Ceph I. Frontal Ceph
Click on grid cell for a Preview image
Click here to see all Preview images
lick_h 1. 5/8/1967 6y 11m
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2 4/26/1958 7y 9m
3. 1/2/1969 8y 5m
º 2/12/1970 9 y 7m
s 3/15/1971 10y 8m
6 5/15/1972 11y 10m
7 4/10/1973 12y 9m
8 5/15/1974 13y 10m
9. 5/29/1975 14y 10m
10 8/26/1976 15y 1m
Figure 6. Typical collection inventory page entry for a single subject.
from the database that powers the website itself. Similar arrays are avail-
able for most but not all of the images in the collection. An enlarged
view four of these buttons is shown at the bottom of Figure 7. The next
four figures demonstrate the data-accessing function of these four buttons.
Clicking on the Preview Images button shown in Figure 7 yields
a display of thumbnail lateral cephalograms for all time points available
for the subject being viewed (Fig. 8). By clicking on any thumbnail of
interest, the viewer can transfer attention immediately to enlarged images
from that time point that is analogous to Figure 7. (Figure 7 has been re-
formatted for display in the current paper. The individual thumbnails in
the actual display are larger considerably and more detailed than the ones
shown here.)
Clicking on the Data Tables button in Figure 7 implements the
display of tabulated numerical data available for this individual subject
(Fig. 9). The first table contains Case 001's measured value for each of
approximately twenty conventional hard tissue cephalometric measures
at each age and their changes through time. A second table containing the








306
Baumrind and Curry
Tº Tº TE-TDR-T E-T Eº Dº Dº
Figure 7. Full screen view of an image from a single time point with two rows of
function buttons beneath.
coordinate values for each landmark used in the calculation of these
measures also is available.
Behind the images displayed on the site is a numerical database
of cephalometric landmark locations. This database is used to facilitate
searches of the website images based on Standard cephalometric meas-
urements. The measurements are based on the previously determined
locations of a number of anatomical cephalometric landmarks. Although
each landmark in the database is the average of two or more independent
estimates, it is to be expected that different clinicians and investigators
may differ in their precise definitions of the landmarks and, hence, dis-
agree about their precise locations.

307
AAOF Craniofacial Growth Legacy Collection
Figure 8. Thumbnail images for the lateral cephalograms at all available time
points for Case 001 of the Mathews collection.
sella Nasiº Hard super palatal plane super Mandibular Border sella Nasion soft super ACB soft
Anatomic Angular and Linearly *
ollection UOP Mathews Grow ºn Study Subject 00
Image 1 - Age 7 2 - Age 8 - 3 - Age 8 || 4 - Age 10 || 5 - Age 11
asure value value deit
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SNE - -
anº
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sºle NA ºs. 97.0 m
| N/A -
4.2 97.1 -
Mathews collection.
5 - Age 12 7 - Aſ -
alue Deltavalue Deltavalue Delta value Delta value Deltavalue Delta value Delta value Delta
Figure 9. A representative portion of the available tables for Case 001 of the
13 || 8 - Age 14 9 - Age 15 10 - Age 15.
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|image 1-Age 7, 2-A.
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3.0 p.s.
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308
Baumrind and Curry
For this reason, it is desirable that viewers have available a
mechanism for knowing where each landmark actually was located on
each image in the data set; the Overlay button, therefore, is provided.
Pressing on this button yields the display of a map of the current image
showing the precise position at which each landmark has been located
(Fig. 10). As a further control against ambiguity, the name of each land-
mark can be displayed at its location by pressing the Labels button (Fig.
11). We believe that information from Figures 10 and 11 will be of con-
siderable utility in the teaching of cephalometric principles to dental stu-
dents and novice orthodontic residents.
oveney -
Tº TE-TDEC El E Nº Lº
contrast- contrast- Bi Pºsº | Cº- Lºs
Figure 10. Overlay showing locations of all landmarks whose coordinates are
available on the nine year four month lateral cephalogram for case 001 of the
Mathews sample.

309
AAOF Craniofacial Growth Legacy Collection
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- | nvert Lighten Daken Redraw
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Figure 11. The lateral cephalogram from Figure 10 with the names of all avail-
able landmarks displayed.
A number of other functions were developed during phase 1 and
already are available on the website. The most notable of these is the
Search mechanism accessible through a link located at the bottom of the
homepage navigation bar (Fig. 12). Even at its early stage of develop-
ment, the search function already enables the user to query any or all col-
lections on the site for cases for specific demographic characteristics or
for particular values for any cephalometric measurement available in the
database. When numerical values found through search are found to be
of special interest, the images from which they originated can be dis-
played directly through links made available in the searching process.
We believe this mechanism has great potential value for use in construct-
ing subsamples from the collection for future hypothesis testing research.

310
Baumrind and Curry
| search the AAof collections once your search results are returned, you can request delivery of the full size images.
ºption 1-search by Collection and Demographic Information
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Hºmº Pan- select Male or Female vºlcases from the Any *collection, where the
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Inormation Age at First Film is Les º years, and the
Abou-ºº. age stussº Film is GreaterThan * years, and
bo-tº-5- Angle ---- *Any º
con-
Co-ºn-Sºº-
| search
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D-criptions option 2 search by conventional cephalometric Measurement and age
ºverwº- - - -
... ." List Timepoints for subjects from Any
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Denve-ºn-h where the value º SNAAngle
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Foºth ºn
low-Growth - -
Mathew-ºn-ºn -
Michigan Growth
Diegon Growth - - - - - -
Browse Images option 3: search by conventional cephalometric Measurement changes -
co-on-ºuth anoth - - - -
Buºngºondrowth List the subjects º * Collection
Denversiºn
Felº Long where a value of sºngs * between the ages of -
Foºth twin
low-Growth -
Mºneº-Growth and the change in SNA.Angle * between the ages of
Michigan Growth - - -
Diegon Growth - - - - -
sº cº-
search collections Search Collections
Search and Request
Figure 12. Query form for searching the collections.
IMPLEMENTATION OF STAGE II
Based on the success of stage I, the AAOF has authorized fund-
ing of the second and final stage of its participation in the legacy collec-
tion project. The goal is to acquire and make available a set of approxi-
mately 1000 case series that roughly are distributed equally among par-
ticipating collections. In this phase, a strong attempt is being made to
collect a stratified random sample that is representative of the holdings of
the individual collections weighted to represent Angle Class III and An-
gle Class II cases more heavily than they are represented in the general
population. This approach is being taken on the grounds that these cate-
gories generally represent the greatest challenges to therapeutic interven-
tion in Orthodontics.
The system will be capable of incorporating data from serial im-
ages of various types including lateral, frontal, oblique, panoramic and
periapical x-ray images of the skull and teeth, as well as quantifiable
three-dimensional (3D) renderings of dental study casts. Collateral
growth records such as wrist and long bone x-ray images and anthro-
pometric measurements may be included when available. The system
will be designed to accommodate remote input from craniofacial investi-







3 ||
AAOF Craniofacial Growth Legacy Collection
gators, clinicians and students at different venues throughout the world.
The input part of the system will include provision for remote data acqui-
sition including image calibration and will accommodate replicate esti-
mates of landmark location from evaluators at different locations.
A search mechanism integrated into the system will make it pos-
sible to output statistics for individuals and groups of subjects with dif-
ferent patterns of craniofacial and dental development. Searches by re-
motely located users will be executable based on demographic character-
istics as well as large number of measured and computed parameters.
The availability of this system will facilitate the collection of
otherwise unobtainable historical control data on developmental changes
through time in untreated subjects with different craniofacial patterns and
dental configurations. In this way, it will become possible to partition
growth effects from treatment effects in future, studies of the effective-
ness of various therapeutic interventions.
CONCLUSIONS
In addition to its primary role of preserving irreplaceable longi-
tudinal records of craniofacial development, the AAOF Lexington Leg-
acy Growth Collection represents an important landmark in the devel-
opment of open collaborative databases for orthodontic research and
teaching. For the first time, investigators from several different institu-
tions have joined together to make original materials from their collec-
tions available to their colleagues at other institutions and to the ortho-
dontic community via the Internet. The collaborating curators and their
institutions are listed in Table 3.
This important collaboration has been made possible through the
combined efforts of the orthodontic community under the leadership of
the AAOF, its Board of Directors and its Executive Vice President, Rob-
ert Hazel. The project they conceived and sponsored has been funded by
the members and friends of the AAO acting through the Legacy 300, a
group of orthodontists and friends organized specifically to support this
project.
In addition, we need to recognize the seminal contributions of
the founders and investigators who conceived and developed the individ-
ual participating collections many years ago and whose devoted work
will be memorialized on the website itself. Finally, we wish to recognize
the support and dedication of the faculty and residents of a large number of
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Baumrind and Curry
Table 3. Available growth collections.

PARTICIPATING
COLLECTION
INSTITUTION
CURATOR
Bolton-Brush Growth
Case Western University
Dr. Mark Hans
Burlington Growth
University of Toronto
Dr. Bryan Tompson
Denver Growth
University of Oklahoma
Dr. Frans Currier
Fels Longitudinal
Wright State University
Dr. Richard Sherwood
Forsyth Twin
Forsyth Institute
Dr. Phil Stashenko
Iowa Growth
University of Iowa
Dr. Tom Southard
Mathews Growth
University of the Pacific
Drs. Shelly Baumrind &
Heesoo Oh
Michigan Growth
University of Michigan
Dr. James A. McNamara
Oregon Growth
Oregon Health & Sciences
University
Drs. David Covell &
Jennifer Crowe
teaching programs who have helped in gathering the data that make it
possible for the first time to search a substantial collection of craniofacial
growth records remotely using classical orthodontic criteria.
Thus, the AAOF Legacy Collection is both a link to the past and
a vision of the future of the orthodontic specialty. It is a work in pro-
gress, dynamically changing with the addition of new material and new
search capabilities. We invite the reader to explore its current status at
www.AAOFLegacy Collection.org.
REFERENCES
Arya BS, Savara BS, Thomas DR. Prediction of first molar occlusion.
Am J Orthod 1973;63:610-621.
Baccetti T, Franchi L, McNamara JA Jr. The Cervical Vertebral
Maturation (CVM) method for the assessment of optimal treatment
timing in orthopedics. Semin Orthod 2005; 11:119-129.
Ball G, Woodside D, Tompson B, Hunter WS, Posluns J. Relationship
between cervical vertebral maturation and mandibular growth. Am J
Orthod Dentofacial Orthop 2011; 139:e455–e461.
Baumrind S, Ben-Bassat Y, Bravo LA, Korn EL, Curry S. Partitioning
the components of tooth displacement in the maxilla by the compari-
son of data from three cephalometric superimpositions. Angle Orthod
1996:66; 111-124.
Baumrind S, Ben-Bassat Y, Korn EL, Bravo LA, Curry S. Mandibular
remodeling measured on cephalograms: 1. Osseous changes relative
3.13
AAOF Craniofacial Growth Legacy Collection
to superimposition on metallic implants. Am J Orthod Dentofacial
Orthop 1992a;102:134-142.
Baumrind S, Ben-Bassat Y, Korn EL, Bravo LA, Curry S. Mandibular
remodeling measured of cephalograms: 2. A comparison of informa-
tion from implant and anatomical best fit superimpositions. Am J Or-
thod Dentofac Orthop 1992b;102:227-238.
Baumrind S, Korn EL. Post-natal width changes in the internal structures
of the human mandible: A longitudinal three-dimensional cephalo-
metric study using implants. Eur J Orthod 1992; 14:417-426.
Baumrind S, Korn EL, Ben-Bassat Y, West EE. The quantitation of max-
illary remodeling: 1. A description of osseous changes relative to su-
perimposition on metallic implants. Am J Orthod 1987a;91:29-45.
Baumrind S, Korn EL, Ben-Bassat Y, West EE. The quantitation of max-
illary remodeling: 2. Masking of remodeling effects when an “ana-
tomical” method of superimposition is used in the absence of metallic
implants. Am J Orthod 1987b;91:463-474.
Baumrind S. NIH-NIDR Grant #R01-DE03598, Dentofacial Effects of
Forces to Retract the Maxilla, 1971-1990.
Baumrind S. NIH-NIDR Grant #R01-DE03703, Integrated Three Di-
mensional Craniofacial Measurement, 1972-1986.
Behrents RG. An Atlas of Growth in the Aging Craniofacial Skeleton.
Monograph 18, Craniofacial Growth Series, Center for Human
Growth and Development, The University of Michigan, Ann Arbor,
1986.
Behrents RG. Growth in the Aging Craniofacial Skeleton and An Atlas of
Growth in the Aging Craniofacial Skeleton. Monograph 17, Craniofa-
cial Growth Series, Center for Human Growth and Development, The
University of Michigan, Ann Arbor, 1985.
Blanchette ME, Nanda RS, Currier GF, Ghosh J, Nanda SK. A longitu-
dinal cephalometric study of the soft tissue profile of short- and long-
face syndromes from 7 to 17 years. Am J Orthod Dentofacial Orthop
1996; 109:116-131.
Broadbent BH Sr, Broadbent BH Jr, Golden WH. Bolton Standards of
Dentofacial Developmental Growth. The CV Mosby Co., 1975.
Buck DL, Brown CM. A longitudinal study of nose growth from ages 6
to 8. Ann Plast Surg 1987;18:310-313.
Edwards CB, Marshall SD, Qian F, Southard KA, Franciscus RG,
Southard TE. Longitudinal study of facial skeletal growth completion
314
Baumrind and Curry
in three dimensions. Am J Orthod Dentofacial Orthop 2007; 132:762–
768.
Eslambolchi S, Woodside DG, Rossouw PE. A descriptive study of
mandibular incisor alignment in untreated subjects. Am J Orthod
Dentofacial Orthop 2008; 133:343-353.
Formby WA, Nanda RS, Currier GF. Longitudinal changes in the adult
facial profile. Am J Orthod Dentofacial Orthop 1994; 105:464–476.
Gu Y, McNamara JA Jr. Cephalometric superimpositions. Angle Orthod
2008;78:967–976.
Gu Y, McNamara JA Jr. Mandibular growth changes and cervical verte-
bral maturation: A cephalometric implant study. Angle Orthod 2007;
77:947–953. -
Hesby RM, Marshall SD, Dawson DV, Southard KA, Casko JS, Francis-
cus RG, Southard TE. Transverse skeletal and dentoalveolar changes
during growth. Am J Orthod Dentofacial Orthop 2006; 130:721-731.
Hoffelder LB, Lima EM, Martinelli FL, Bolognese AM. Soft-tissue
changes during facial growth in skeletal Class II individuals. Am J
Orthod Dentofacial Orthop 2007;131:490–495.
Hunter WS, Baumrind S, Moyers RE. An inventory of U.S. and Cana-
dian growth record sets. Am J Orthod Dentofacial Orthop 1993; 103:
545–555.
Hunter WS, Baumrind S, Popovich F, Jorgensen G. Forecasting the tim-
ing of peak mandibular growth in males by using skeletal age. Am J
Orthod Dentofacial Orthop 2007;131:327–333.
Hunter WS, Popovich F, Baumrind S, Jorgensen G. Skeletal age and
peak mandibular growth velocity at puberty. In: McNamara JA Jr,
Kelly KA. Treatment Timing: Orthodontics in Four Dimensions.
Monograph 39, Craniofacial Growth Series, Department of Orthodon-
tics and Pediatric Dentistry and Center for Human Growth and De-
velopment, The University of Michigan, Ann Arbor, 2002;185-197.
Knott VB. Growth of the mandible relative to a cranial base line. Angle
Orthod 1973:43:305-313.
Kolodziej RP, Southard TE, Southard KA, Casko JS, Jakobsen JR.
Evaluation of antegonial notch depth for growth prediction. Am J Or-
thod Dentofac Orthop 2002;121:357-363.
Korn EL. NIH-NIDR Grant #DE07332 Utility of Metallic Implants in
Measuring the Treatment Effects of Orthodontic Treatment 1984–
1988.
315
AAOF Craniofacial Growth Legacy Collection
Korn EL, Baumrind S. Transverse development of the human jaws be-
tween the ages of 8.5 and 15.5 years studied longitudinally with use
of implants. J Dent Res 1990;69:1298–1306.
Leslie LR, Southard TE, Southard KA, Casko JC, Jakobsen JR, Tolley
EA, Hills SL, Carolin C, Logue M. Prediction of mandibular growth
rotation: Assessment of the Skieller Bjork, and Linde-Hansen
method. Am J Orthod Dentofacial Orthop 1998; 114:659-667.
Lewis AB, Roche AF. Late growth changes in the craniofacial skeleton.
Angle Orthod 1988:58:127-135.
Lewis AB, Roche AF. The saddle angle: Constancy or change? Angle
Orthod 1977:47:46-54.
Lewis AB, Roche AF, Wagner B. Pubertal spurts in cranial base and
mandible: Comparisons within individuals. Angle Orthod 1985:55:17-30.
Marshall S, Dawson D, Southard K, Lee A, Casko J, Southard T. Trans-
verse molar movements during growth. Am J Orthod Dentofac Or-
thop 2003;124:615-624.
McNamara JA Jr. Components of Class II malocclusion in children 8-10
years of age. Angle Orthod 1981;51:177-202.
McNamara JA Jr, Bookstein FL, Shaughnessy TG. Skeletal and dental
changes following functional regulator therapy on Class II patients.
Amer J Orthod 1985;88:91-110.
McNamara JA Jr, Howe RP, Dischinger TG. A comparison of the Herbst
and Fränkel treatment in Class II malocclusion. Am J Orthod
Dentofacial Orthop 1990;98:134-144.
Meng HP, Goorhuis J, Kapila S, Nanda RS. Growth changes in the nasal
profile from 7 to 18 years of age. Am J Orthod 1988;94:317-326.
Moyers RE, Riolo ML, Guire KE, Wainright RL, Bookstein FL. Differ-
ential diagnosis of Class II malocclusions: Part I. Facial types associ-
ated with Class II malocclusions. Am J Orthod 1980;78:477-494.
Moyers RE, van der Linden FPGM, Riolo ML, McNamara JA Jr. Stan-
dards of Human Occlusal Development. Standards of Human Occlu-
sal Development. Monograph 5, Craniofacial Growth Series, Center
for Human Growth and Development, The University of Michigan,
Ann Arbor, 1976.
316
Baumrind and Curry
Nakamura S, Savara BS, Thomas DR. Norms of size and annual incre-
ments of the sphenoid bone from four to sixteen years. Angle Orthod
1972:42:35–43.
Nanda RS, Ghosh J. Longitudinal growth changes in the sagittal relation-
ship of maxilla and mandible. Am J Orthod Dentofacial Orthop 1995;
| 07:79–90.
Ohtsuki F, Mukherjee D, Lewis AB, Roche AF. A factor analysis of cra-
nial base and vault dimensions in children. Am J Phys Anthropol
1982:58:271-279.
Riolo ML, Moyers RE, McNamara JA Jr, Hunter WS. An Atlas of Cra-
niofacial Growth. Cephalometric Standards from The University
School Growth Study, The University of Michigan. Monograph 2,
Department of Orthodontics and Pediatric Dentistry and Center for
Human Growth and Development, The University of Michigan, Ann
Arbor, 1974.
Sanin C, Savara BS, Clarkson QC, Thomas DR. Prediction of occlusion
by measurements of the deciduous dentition. Am J Orthod 1970a;
57:561-572.
Sanin C, Sekiguchi T, Sen Savara B.S. A quick method for prediction of
closure of diastema between permanent central incisors. Int J Orthod
1970b:8:77-79.
Savara BS, Steen JC. Timing and sequence of eruption of permanent
teeth in a longitudinal sample of children from Oregon. J Am Dent
Assoc 1978;97:209-214.
Savara BS, Takeuchi Y. Anatomical location of cephalometric landmarks
on the sphenoid and temporal bones. Angle Orthod 1979;49:141-149.
Sekiguchi T, Savara BS. Variability of cephalometric landmarks used for
face growth studies. Am J Orthod 1972;61:603-618.
Sekiguchi T, Savara BS, Arya B.S. Norms of size and annual increments
of six anatomical measures of the cranium in boys and girls from four
to fifteen years of age. Am J Phys Anthropol 1973:39:49-55.
Sherwood RJ, Duren DL, Mahaney MC, Blangero J, Dyer TD, Cole SA,
Czerwinski SA, Chumlea WC, Siervogel RM, Choh AC, Nahhas RW,
Lee M, Towne B. A genome-wide linkage scan for quantitative trait
loci influencing the craniofacial complex in humans (Homo sapiens
sapiens). Anat Rec (Hoboken) 2011:294:664-675.
317
AAOF Craniofacial Growth Legacy Collection
Snodell SF, Nanda RS, Currier GF. A longitudinal cephalometric study
of transverse and vertical craniofacial growth. Am J Orthod Dentofa-
cial Orthop 1993;104:471-483.
Suri S, Ross RB, Tompson BD. Craniofacial morphology and adolescent
facial growth in Pierre Robin sequence. Am J Orthod Dentofacial Or-
thop 2010; 137:763-774.
Tanaka EM, Sato S. Longitudinal alteration of the occlusal plane and
development of different dentoskeletal frames during growth. Am J
Orthod Dentofacial Orthop 2008;134:602.el-el 1.
Wieslander L. Intensive treatment of severe Class II malocclusions with
a headgear-Herbst appliance in the early mixed dentition. Am J Or-
thod 1984;86:1–13.
Wieslander L. Long-term effect of treatment with the headgear-Herbst
appliance in the early mixed dentition. Stability or relapse? Am J Or-
thod Dentofacial Orthop 1993;104:319-329.
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