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ArthritiS in Color: AdvAnCed imAging oF ArthritiS iSBn: 978-1-4160-4722-3
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Library of Congress Cataloging-in-Publication Data
Bruno, michael A.
Arthritis in color : advanced imaging of arthritis / michael A. Bruno, timothy J. mosher, garry e.
gold.—1st ed.
p. ; cm.
includes bibliographical references.
iSBn 978-1-4160-4722-3
1. Arthritis—imaging. i. mosher, timothy J. ii. gold, garry e. iii. title.
[dnlm: 1. Arthritis, rheumatoid—diagnosis. 2. diagnostic imaging—methods.
3. magnetic resonance imaging—methods. 4. osteoarthritis—diagnosis. We 346 B898a
2009]
rC933.B785 2009
616.7′220754—dc22 2008050298
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last digit is the print number: 9 8 7 6 5 4 3 2 1
To our parents, who made it possible—and to our children,
who make it all worthwhile.
Michael A. Bruno
Timothy J. Mosher
Garry E. Gold
W
A A
bout the uthors
Michael A. Bruno, MS, MD, is Associate Professor of Radiology
and Medicine and Director of Quality Management Services at
Penn State University College of Medicine and the Milton S.
Hershey Medical Center in Hershey, Pennsylvania, where in
2001 he initiated and served as the first program director of the
Musculoskeletal Radiology Fellowship training program. Prior
to that, Dr. Bruno was Assistant Professor of Radiology and
Clinical Director of Emergency Radiology at Vanderbilt Univer-
sity School of Medicine, where he first developed his research
interest in the application of Doppler ultrasonography for
assessment of rheumatoid arthritis and related diseases. In 1998,
he initiated the MSK Radiology fellowship training program at Vanderbilt and served
as its program director until relocating to Hershey Medical Center in 1999. Dr.
Bruno specializes in musculoskeletal imaging and nuclear medicine.
Dr. Bruno’s research efforts over the past decade have been primarily focused on
functional imaging, emphasizing quantified power Doppler ultrasonography. Dr.
Bruno’s arthritis imaging research has been supported by private foundations includ-
ing a 1998 seed grant from the Radiological Society of North America (RSNA) and
the National Institutes of Health (NIH). He is a frequent invited lecturer and keynote
speaker on arthritis imaging and other musculoskeletal and practice quality improve-
ment topics at national and international scientific meetings. He has written several
scientific papers on these topics and serves as a reviewer for multiple medical and
scientific journals. Dr. Bruno has also served on the editorial advisory panel for the
American Journal of Roentgenology (AJR) and as a medical editor for the e-medicine
online radiology textbook. He is a member of The RSNA Policy & Practice Commit-
tee, the “Examination of the Future” Development Committee for Musculoskeletal
Radiology, the Research Committee of the Society of Skeletal Radiology and the
RSNA’s Roster of Distinguished Scientific Advisors. He lives in Hummelstown,
Pennsylvania.
Ultrasound Evaluation of Rheumatoid Arthritis; MRI in Rheumatoid Arthritis
Timothy J. Mosher, MS, MD, is Professor of Radiology
and Orthopaedics and Chief of Musculoskeletal Radiology,
MRI and Radiology Research at the Milton S. Hershey Medical
Center, Penn State College of Medicine in Hershey,
Pennsylvania.
Dr. Mosher’s research career has emphasized the use of MRI
in cartilage imaging and osteoarthritis. He is an internationally
recognized expert in high-field MR imaging of articular carti-
lage and pioneered the use of T2 mapping. His research has been
supported by an RSNA Research Scholar Grant, Clinical Science
Grants from the Arthritis Foundation, and R-01 Grants from the NIH. He has
written or coauthored more than 25 original scientific articles, peer-reviewed elec-
tronic journal articles, and book chapters on the results of his extensive research. He
has lectured extensively on MRI cartilage imaging nationally and abroad and has
served on several national and international advisory committees and editorial
boards, including the RSNA Distinguished Roster of Scientific Advisors, NIH Arthri-
tis Imaging Study Sections, and ISMRM and RSNA Scientific Committees. He lives W
in Elizabethtown, Pennsylvania.
viii About the Authors
Functional Anatomy and Structure of the “Osteochondral Unit”; Clinical MRI of
Osteoarthritis and Osteochondral Injury; New MRI Techniques for Osteoarthritis, Bio-
chemical and Functional Techniques for Cartilage Imaging
Garry E. Gold, MSEE, MD, is Associate Professor of Radiology
and (by courtesy) Bioengineering and Orthopedics at Stanford
University School of Medicine, specializing in musculoskeletal
radiology.
Dr. Gold’s research in rapid MRI for evaluation of osteoar-
thritis is funded by the NIH and emphasizes the development
of new and optimal MRI sequences for the evaluation of articu-
lar cartilage and related topics. He has written or coauthored
more than 60 articles in peer-reviewed journals, 2 book chapters
and 15 invited reviews. He is on the editorial boards of two
journals and has served on the Scientific Program Committee for the International
Society for Magnetic Resonance in Medicine. He is a frequent invited lecturer and
has made more than 120 scientific presentations of his research at national and
international venues. In addition, he has won multiple awards for his work in carti-
lage MRI. He lives in Stanford, California, with his family, including new twins and
a wonder-dog named Humboldt.
Technical Considerations for Clinical MRI of Arthritis; New MRI Techniques for
Osteoarthritis
W
A C
bout the ontributors
Sandip Biswal, MD, is Assistant Professor of Radiology,
Musculoskeletal Division, and a Member of the Molecular
Imaging Program at Stanford University School of Medicine,
in Stanford, California.
Molecular Imaging of Rheumatoid Arthritis and Osteoarthritis
Roland Hustinx, MD, PhD, is chief of the division of nuclear
medicine, University Hospital of Liège, Belgium. Dr. Hustinx’s
research has focused on PET imaging. His primary field of inter-
est is the clinical validation of alternative radiotracers. He started
his scientific career with a 2-year research fellowship at the Uni-
versity of Pennsylvania, Philadelphia. He is the current General
Secretary of the Belgian Society of Nuclear Medicine and serves
on the editorial board for the two major journals of nuclear
medicine. He has written or coauthored more than 70 articles
in peer-reviewed scientific publications and 12 book chapters.
Nuclear (Scintigraphic) Methods and FDG PET in Rheumatoid Arthritis and
Osteoarthritis
Michael P. Recht, MD, is a musculoskeletal radiologist and serves as chairman of
the department of business development for the Cleveland Clinic Imaging Institute.
His main area of research interest is MRI of articular cartilage.
Surgical Approaches for Osteochondral Repair and Postoperative Imaging
Considerations
Clio Ribbens, MD, PhD, is Head of Clinic in the rheumatology
department of the University Hospital of Liège, Belgium. Her
main field of interest is rheumatoid arthritis. She started her
scientific career as a fellow of the Belgian National Fund for
Scientific Research and studied both in vitro and in vivo bio-
markers of arthritis such as cytokines and matrix metallo-
proteinases. Her clinical work focuses on the assessment of
inflammation in patients using imaging modalities such as
ultrasonography and PET. She was the Scientific President of the
Belgian Congress of Rheumatology in 2007.
Nuclear (Scintigraphic) Methods and FDG PET in Rheumatoid Arthritis and
Osteoarthritis
Richard J. Wakefield, BM, MD, MRCP, is Senior Lecturer in Rheumatology, Aca-
demic Unit of Musculoskeletal Disease, University of Leeds and Leeds Infirmary,
United Kingdom. He is also co-chair of the OMERACT Interest Group on the use W
of ultrasonography in rheumatoid arthritis. He is one of the foremost recognized
x About the Contributors
experts in this topic and a frequent speaker at international meetings, as well as a
regular teacher on national and international musculoskeletal ultrasonography
courses. Dr. Wakefield qualified from Southampton University, UK in 1991. He
began his rheumatology career in Leeds as a research fellow in 1997 when he first
developed his interest in ultrasonography and early arthritis. In 2001, he became
Lecturer / Honorary Registrar in Rheumatology at the University of Leeds and in
2004 became Senior Lecturer/Honorary Consultant. His major research interests
include validation of ultrasound (MD thesis, University of Leeds 2006), ultrasound
in early arthritis, and development of management pathways using imaging and
training and education. In addition to his having been co-chair of the OMERACT
Ultrasound Special Interest Group since 2004, he was also the coordinator for the
ACR Musculoskeletal Ultrasound Group from 2002 to 2005. He organized the BSR
ultrasonography course in Harrogate in 2004, the 2nd Advanced EULAR ultraso-
nography course in Leeds in October 2006, and coordinated the 7th BSR Musculo-
skeletal ultrasonography course in Leeds in 2008. Dr. Wakefield has been the author
or coauthor of 60 peer-reviewed articles relating to ultrasonography and several book
chapters.
Ultrasound Evaluation of Rheumatoid Arthritis
Lawrence M. White, MD, FRCPC, is Professor of Medical
Imaging and Surgery (Orthopedics) and Head of the Division
of Musculoskeletal Imaging at the University of Toronto.
Surgical Approaches for Osteochondral Repair and Postoperative
Imaging Considerations
W
P
reface
This book reviews the state of the art as well as current research and recent advances
in the use of MRI, ultrasonography, computed tomography (CT), and nuclear
and molecular imaging (MI) for the diagnosis and treatment of arthritis, especially
rheumatoid arthritis (RA) and osteoarthritis (OA). The first section of the book
focuses on the clinical state of the art, emphasizing methods that are currently avail-
able and in routine clinical use throughout the world; the second portion is forward-
looking and emphasizes new and experimental methods and imaging strategies,
including cutting-edge molecular imaging research, which is the topic of the final
chapter.
Arthritis is a leading cause of disability worldwide. OA is the most common type
of arthritis, affecting an estimated 20.7 million adults in the United States alone (U.S.
Government data). RA is a generally more serious and debilitating disease, affecting
more than 10 million persons of all ages in the United States. These diseases are
among the most significant causes of disability in our society, with costs in lost work
and productivity estimated at over $1 billion annually. As our world population ages,
the impact of arthritis on the human condition, quality of life, and world economy
will take on an even larger and increased significance.
In recent years, conservative management of arthritis has been replaced with new,
aggressive drug therapies. These, in turn, have created an unprecedented demand
for more rapid assessment of disease activity and response to treatment. Necessity
is, as is often said, the mother of invention—but in a very real sense today’s arthritis
patients benefit from a lucky convergence of advances in imaging technology (that
have coincidentally occurred in time to be of use) and new biopharmacologic thera-
pies. More powerful drugs offer new hope for relief but have also created significant
new challenges for physicians and pose some risks for patients. The pharmaceutical
industry has invested heavily in developing new drugs for arthritis, and articles in
the Wall Street Journal* and other financial and business sources have speculated
that drugs targeted to joint diseases—and especially RA—will become the premier
growth market for the pharmaceutical industry, attracting considerable capital for
research and development in both traditional and newer biotechnology firms.
These new disease-modifying and biologic response-altering drug therapies are
extremely aggressive by historical standards in rheumatology; accordingly any sort
of rapid assessment “feedback” that can be provided is of great value both to guide
the clinician and to help justify the risks and expense involved in their use. Tradi-
tional radiographs, while still the mainstay of diagnosis and classification of disease,
are insufficient for this purpose. Conventional radiography is limited in that it
depicts the complex soft tissue changes in arthritis only in terms of the presence or
absence of gross swelling and the bony changes only as the cumulative sum of the
long-term effects of disease activity (e.g., the development of permanent bony
deformities, such as osteophytes, joint subluxations, and erosions). To assess the
severity of disease or response to treatment, radiographs essentially require a large
number of observations (i.e., serial imaging at intervals), with painstaking compari-
son of the progression of small or subtle deformities observed over an extended
period of time—and even when done meticulously and rigorously will provide only
a very limited and incomplete portrayal of the dynamic disease processes involved
in the complex, chronic disease entities as they affect an individual patient.
*For example, see “Enbrel Approved by FDA for Early Stage Rheumatoid Arthritis” in The Wall Street W
Journal, published April 12, 2000.
xii Preface
Because of these limitations, radiology researchers have turned their efforts toward
adapting newer, advanced imaging methods and technologies toward the assessment
of articular cartilage in OA and for assessment of disease activity by various means
in inflammatory arthritis (mostly RA and related diseases). Gaining an understand-
ing and mastery of these methods and their implications going forward is both a
difficult challenge and a tremendous opportunity for the field of diagnostic radiol-
ogy. Integrating these new methods rationally into the day-to-day management of
patients is the 21st century challenge to the field of rheumatology.
This book is intended as a resource for both fields, and its goal is to efficiently and
comprehensively educate diagnostic radiologists, rheumatologists, and other special-
ists as to the state of the art, current methodologies, and future research directions
in this dynamic and rapidly evolving arena. In doing so, we have drawn from a huge
and rapidly growing volume of clinical and research literature in the field—some
quite recent and some published over the past 2 decades or more—in an attempt to
provide a broad perspective on the field, as well as to distill a refined elixir of the
most salient facts, organized in such a way as to make the topic as clear and as simple
as possible. I am extremely indebted to my coauthors and the several outstanding
contributors to this volume, all of whom are distinguished leaders in their respective
fields, for giving so generously of their time and expertise to produce this
textbook.
The title of this book was intended as an homage to the now classic radiology
textbook from which so many of us learned the plain film diagnosis of the arthritides,
Arthritis in Black and White, by Drs. Anne Brower and Donald J. Flemming, soon to
be in its third edition. This landmark text, which to this day remains an intellectual
staple and bedrock textbook for both radiologists and rheumatologists, is by no
means diminished by our efforts here. To the contrary, we hope with our new
textbook to build upon the solid foundation of Arthritis in Black and White, and
we have attempted to provide in this volume a resource that will serve as a logical
continuation on the topic of imaging in arthritis for the interested reader at all
levels of professional training and experience. The ultimate goal in this learning
and knowledge-distilling exercise is the benefit of our patients—those many, many
people suffering from debilitating joint disease, who as a group have so often given
of themselves so selflessly to be subjects for our research, in order that we might
learn enough to help others in the future.
Michael A. Bruno
W
Part I
Advanced Arthritis
Imaging in Clinical
Practice
W
