The Pathophysiologic Basis of Nuclear

Medicine
Abdelhamid H. Elgazzar
Editor

The Pathophysiologic
Basis of Nuclear
Medicine
Third Edition
Editor
Abdelhamid H. Elgazzar, MD, FCAP
Department of Nuclear Medicine
Faculty of Medicine
Kuwait University Health Science Center
Kuwait City
Kuwait

ISBN 978-3-319-06111-5 ISBN 978-3-319-06112-2 (eBook)

DOI 10.1007/978-3-319-06112-2
Springer Cham Heidelberg New York Dordrecht London

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To my children the superb humans
Foreword to First Edition

Diagnostic imaging studies may be interpreted in one of two ways. The initial
approach is that of the “imager”, dealing solely with pattern recognition. In
this respect, the experienced observer will surely out-perform the younger
physician who possesses a more limited fund of such knowledge in his or her
memory bank. The other means of interpreting images draws basic patho-
physiology and clinical knowledge of a disease entity into the interpretive
process. Functional nuclear medicine imaging studies are exquisitely sensi-
tive but notoriously non-specific. For this reason, nuclear medicine is most
often used as a screening tool or as a monitor of changes in function when
therapeutic interventions are performed.
The non-specificity of radionuclide imaging studies makes it particularly
important that nuclear medicine physicians have a broad, in-depth under-
standing of the basic pathophysiology of the disease processes which they are
being asked to study. It is in this area that Dr. Abdelhamid H. Elgazzar and his
many colleagues have excelled. In the following 22 chapters, they provide us
with a lucid, systemic presentation of the pathophysiology associated with
various disease processes and how this knowledge impacts on scintigraphic
interpretations. In addition to the clinical presentations, chapters dealing with
cell structure and function, radiopharmaceutical localization, biologic effects
of ionizing radiation and radionuclide therapy provide very useful informa-
tion. The format employed by this gifted international panel of authors pro-
vides us with an extraordinary text which differs from some of the other fine
publications in our field. It remains true to the very essence of functional
imaging which characterizes the field of nuclear medicine and distinguishes
it from the more morphologically based radiologic imaging procedures.
Both residents and active practitioners of nuclear medicine will profit from
the enormous amount of clinically relevant information provided herein. This
volume will surely enhance our role as well-rounded nuclear medicine physi-
cians, as opposed to being more limited “imagers”. It is only in this manner
that we can fulfill our obligation as true consultants and play a pivotal role in
assisting patient management decisions.
We are most indebted to Dr. Elgazzar and his co-authors for enhancing our
diagnostic skills with this extraordinary textbook.

New York, NY, USA Leonard M. Freeman, MD

vii
Preface to Third Edition

Awareness of the impact of pathophysiology in particular on imaging stud-

ies is critical to the proper practice of nuclear medicine. The correlation of
these basic aspects with the scintigraphic features of various diseases is
further emphasized in this edition. Imaging specialist must appreciate the
patient’s clinical problem and the pathophysiologic changes to fully utilize
nuclear images. Working from this clinical context, the specialist can then
apply his/her understanding of the pathophysiologic basis of disease and
the knowledge of how such pathology may translate into various imaging
patterns. The difference between film reading dealing solely with pattern
recognition and proper interpretation of a clinical scintigraphic image in the
holistic approach integrating clinical, laboratory and pathophysiologic
understanding should be appreciated to achieve proper clinical impact. New
developments in molecular biology, radiopharmaceuticals and hybrid imag-
ing have continued to contribute to the rapid change in the field of nuclear
medicine and molecular imaging. To continue the efforts to accommodate
these changes and be in line with the future direction of nuclear medicine
and molecular imaging, the 3rd edition of The Pathophysiologic Basis of
Nuclear Medicine was developed.
This edition reflects new developments in the area of molecular imaging
with more emphasis given to the basis and application of PET/CT. The chap-
ter on tumor scintigraphy details PET/CT management of individual tumors.
Furthermore the radiopharmaceuticals for PET imaging have been updated
with more details and correlation with pathophysiologic changes such as
hypoxia, angiogenesis and proliferation. The additional information about
clinical and imaging correlation makes this text a very useful companion to
those who are being trained in nuclear medicine technology and clinical
nuclear medicine.
It is my hope that this book will help medical professionals to further
understand what nuclear medicine technology can offer for the diagnosis and
treatment of disease. Deep understanding of the scientific and clinical basis
of the new directions in medical imaging will certainly lead to further
improvements and innovations in this important field of medicine. This
updated edition will hopefully help in the understanding of the field of nuclear
medicine in depth and further advance and improve current diagnostic and
therapeutic modalities in the treatment of disease.

Kuwait City, Kuwait Abdelhamid H. Elgazzar, MD, FCAP

ix
Preface to Second Edition

The field of nuclear medicine is continuing to grow rapidly and incorporating

advances in molecular biology, molecular imaging, and pathophysiology. In
an effort to accommodate these changes and be in line with the future direc-
tion of nuclear medicine, we have updated the first edition of The
Pathophysiologic Basis of Nuclear Medicine, building on its strengths and
making modifications to remedy any weak areas.
To reflect new developments in the area of molecular imaging, a separate
chapter on the basis of positron emission tomography has been included,
more information about therapy using radionuclides has been added, and the
chapters on the cell, radiopharmaceutical uptake, inflammation, bone, respi-
ratory and neurology have been expanded. Furthermore, the clinical aspects
of the role of molecular imaging in nuclear imaging are emphasized, since an
imaging specialist must appreciate the patient’s clinical problem for a full
utilization of nuclear images. For instance, the difference between superficial
film reading and proper interpretation of a clinical scintigraphic image by a
holistic approach has been highlighted. Working from this clinical context,
the specialist can then apply his/her understanding of the pathophysiologic
basis of disease and the knowledge of how such pathology may translate into
various imaging patterns. Awareness of the impact of pathophysiology on
imaging studies is critical to the proper practice of nuclear medicine. The
additional information about clinical and imaging correlation makes this text
an invaluable companion to those who are being trained in nuclear medicine
technology and clinical nuclear medicine.
We extend our appreciation to reviewers of several journals as well as
members of the nuclear medicine community from around the world for their
helpful and motivating feedback, both published and private. It is my sincere
hope that this book will help medical professionals to further understand
what nuclear medicine technology can offer in the diagnosis and treatment of
disease. A deeper understanding of the scientific and clinical basis of new
directions in medical imaging will certainly lead to further modifications and
new innovations. I also hope that this revised text will help to advance knowl-
edge in the field of nuclear medicine and improve currently available diag-
nostic and therapeutic tools in the treatment of patients with various
diseases.

Kuwait City, Kuwait Abdelhamid H. Elgazzar, MD, FCAP

xi
Preface to First Edition

There is a great difference between superficial reading of a film and proper

interpretation of a clinical scintigraphic image by an imaging specialist. Fully
utilizing the clinical image, the imaging specialist evaluates both the ana-
tomical and the physiological structure of the human body. First the specialist
must appreciate the patient’s clinical problem. Working from this clinical
context, he then applies his understanding of the pathophysiological basis of
disease and his knowledge of how such pathology may translate into various
imaging patterns. This awareness of the impact of pathophysiology on imag-
ing studies is critical to the proper practice of nuclear medicine.
Nuclear medicine is a unique and growing medical specialty that contrib-
utes most significantly to our understanding of the functional changes which
accompany disease. In this way, nuclear medicine helps to advance scientific
understanding. Both the diagnostic and the therapeutic aspects of nuclear
medicine rely for their efficacy on the physiological changes produced by dis-
ease. Clearly, a detailed understanding of both normal and morbid pathophysi-
ology is prerequisite to a successful career in this growing field of medicine.
Today nuclear medicine is one of the medical specialties with great oppor-
tunities for innovation and creative thinking. We are fortunate to be practicing
nuclear medicine at a time of rapid scientific progress and significant growth
in our contributions to patient care and well-being. The resources devoted to
nuclear medicine, however, will be most profitably used when both research-
ers and practicing physicians have taken the time to understand the patho-
physiological basis of scintigraphy and radionuclide therapy.
As a practicing nuclear medicine physician and teacher, I know that begin-
ning students and physicians in both radiology and nuclear medicine have in
the past lacked a concise textbook which focuses on the pathophysiological
basis of nuclear medicine. I feel that the contributing authors to this book have
collectively fulfilled this need. In addition, I hope that this book will serve as a
practical reference for practicing radiologists and nuclear medicine physicians.
Given the rapid pace of research in the field of nuclear medicine, keeping up to
date after the completion of formal training is a challenge for all of us.
Along with the contributing authors, I hope that this book will help to
spread medical knowledge and enhance patient care within the field of nuclear
medicine.

Kuwait City, Kuwait Abdelhamid H. Elgazzar, MD, FCAP

xiii
Acknowledgement

My thanks and appreciation goes to Dr. Jehan Alshammari, Mrs. Heba Essam,
Dr. Heba Elgazzar, Dr. Mohamed Sakr, Mrs. Reham Hajji, Mrs. Verovica
Cody-Nurse and Dr. Iman Alshammari, who sincerely supported to make this
edition a reality.

xv
Contents

1 Pathophysiology: General Principles . . . . . . . . . . . . . . . . . . . . 1

Abdelhamid H. Elgazzar
2 The Cell and Tissue Biology . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Shankar Vallabhajosula, Seham Mustafa,
and Abdelhamid H. Elgazzar
3 Basis of Radiopharmaceutical Localization . . . . . . . . . . . . . . 45
Shankar Vallabhajosula and Azu Owunwanne
4 Inflammation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
Abdelhamid H. Elgazzar and Magda Elmonayeri
5 Nuclear Hematology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
Kshitish Chandra Das and Abdelhamid H. Elgazzar
6 Musculoskeletal System. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155
Abdelhamid H. Elgazzar and Dia Shehab
7 Thyroid Gland . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 261
Salil D. Sarkar
8 Parathyroid Gland . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281
Abdelhamid H. Elgazzar and Saud A. Alenezi
9 Adrenal Gland . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305
Abdelhamid H. Elgazzar and Iman Alshammari
10 Genitourinary System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 319
Salil D. Sarkar, Pravin C. Singhal, and Abdelhamid H. Elgazzar
11 Nuclear Oncology 1: Principles of Tumor
Pathology and Biology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 347
Ezzuldin Ibrahim, Ahmad Elkhodary, and Abdelhamid H. Elgazzar
12 Nuclear Oncology 2: Scintigrahic Imaging . . . . . . . . . . . . . . . 369
Razi Muzaffar, Osama Raslan, and Medhat M. Osman
13 Respiratory System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 401
Abdelhamid H. Elgazzar and Mousa Khadada
14 Nuclear Cardiology 1: Myocardial Contractility
and Assessment of Cardiac Function . . . . . . . . . . . . . . . . . . . . 433
Sherif I. Heiba and Mohamad Zubaid

xvii
xviii Contents

15 Nuclear Cardiology 2: Myocardial Perfusion,

Metabolism, Infarction, and Receptor Imaging . . . . . . . . . . . 463
Josef Machac
16 Digestive System 1: Gastrointestinal Tract . . . . . . . . . . . . . . . 529
Fuad A.M. Hassan and Abdelhamid H. Elgazzar
17 Digestive System 2: Liver and Biliary Tract . . . . . . . . . . . . . . 559
Chun K. Kim, Junghyun Joo, and Seokmo Lee
18 Nuclear Medicine Imaging of CNS:
Basis and Clinical Applications . . . . . . . . . . . . . . . . . . . . . . . . 595
James M. Mountz and Rafay Ahmed
19 Lymphoscintigraphy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 671
Arthur Z. Krasnow, Abdelhamid H. Elgazzar,
Nafisa Kazem, and Saud A. Alenezi
20 Basis of Therapeutic Nuclear Medicine . . . . . . . . . . . . . . . . . . 689
Abdelhamid H. Elgazzar, Abdullatif Al-Bader,
and Hussein M. Abdel-Dayem
21 Biological Effects of Ionizing Radiation. . . . . . . . . . . . . . . . . . 715
Abdelhamid H. Elgazzar and Nafisa Kazem

Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 727
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 735
Contributors

Hussein M. Abdel-Dayem, MD, PhD Former Professor, Division of

Nuclear Medicine, Department of Radiology, New York Medical College
and St Vincent Hospital, New York, NY, USA
Rafay Ahmed, MD Fellow, Division of Nuclear Medicine, Department of
Radiology, The University of Pittsburgh Medical Center, Pittsburgh,
PA, USA
Abdullatif Al-Bader, PhD Professor, Department of Pathology,
President, Kuwait University, Kuwait City, Kuwait
Saud A. Alenezi, MD, ABNM, FRCPC Assistant Professor,
Department of Nuclear Medicine, Faculty of Medicine, Kuwait University,
Kuwait City, Kuwait
Iman Alshammari, MD Chairman, Department of Nuclear Medicine,
Farwania Hospital, Kuwait City, Kuwait
Kshitish Chandra Das, MD Former Professor, Department of Pathology,
Faculty of Medicine, Kuwait University Health Science Center,
Kuwait City, Kuwait
Abdelhamid H. Elgazzar, MD, FCAP Diplomate, American Board of
Pathology, Diplomate, American Board of Nuclear Medicine, Professor,
Department of Nuclear Medicine, Faculty of Medicine, Kuwait University,
Kuwait City, Kuwait
Ahmed Elkhodary, MD, PhD Department of Medical Oncology, National
Cancer Institute, Cairo University, Cairo, Egypt
Magda Elmonayeri, MD, PhD Professor, Department of Pathology,
Faculty of Medicine, Ain Shams University, Cairo, Egypt
Fuad A.M. Hassan, MD Professor, Department of Medicine,
Faculty of Medicine, Kuwait University, Kuwait City, Kuwait
Sherif I. Heiba, MD Associate Professor of Radiology, Division of
Nuclear Medicine, Mount Sinai School of Medicine, New York, NY, USA
Ezzeldin Ibrahim, MD, MSc (H. Info), FRCP, FACP
Chief Medical Officer, Director, Oncology Center of Excellence,
International Medical Center, Jeddah, Saudi Arabia

xix
xx Contributors

Junghyun Joo, MD Staff Radiologist, Department of Radiology,

Saint Carollo Hospital, Suncheon, Republic of Korea
Nafisah Kazem, MD Chairman, Department of Nuclear Medicine,
Mubarak Hospital, Jabriya, Kuwait
Mousa Khadada, MD Professor, Department of Medicine,
Faculty of Medicine, Kuwait University, Kuwait City, Kuwait
Chun K. Kim, MD Associate Professor, Division of Nuclear Medicine
and Molecular Imaging, Brigham and Women’s Hospital, Harvard Medical
School, Boston, MA, USA
Arthur Z. Krasnow Associate Professor, Division of Nuclear Medicine,
Department of Radiology, Medical College of Wissonsin,
Milwakee, WI, USA
Seokmo Lee, MD Assistant Professor, Department of Nuclear Medicine,
Inje University College of Medicine, Busan, Republic of Korea
Josef Machac, MD, FACC, FACNM Professor, Division of Nuclear
Medicine, Department of Radiology, Mount Sinai School of Medicine,
New York, NY, USA
James M. Mountz, MD, PhD Professor, Division of Nuclear Medicine,
Department of Radiology, The University of Pittsburgh Medical Center,
Pittsburgh, PA, USA
Seham Mustafa, PhD Associate Professor, Biomedical Sciences
Department, College of Nursing, Public Authority for Applied
Education and Training, Kuwait City, Kuwait
Razi Muzaffar, DO Assistant Professor, Division of Nuclear Medicine,
Department of Radiology, Saint Louis University, Saint Louis, MO, USA
Medhat M. Osman, MD, ScM, PhD Professor, Division of Nuclear
Medicine, Department of Radiology, Saint Louis University,
Saint Louis, MO, USA
Azu Owunwanne Professor, Department of Nuclear Medicine,
Faculty of Medicine, Kuwait University Health Science Center,
Kuwait City, Kuwait
Osama Raslan, MA, MB, BCh, MD, MSc, MBBCh Resident, Division of
Nuclear Medicine, Department of Radiology, Saint Louis University,
Saint Louis, MO, USA
Salil D. Sarkar, MD, FACP Associate Professor, Department of Radiology
(Nuclear Medicine), Chair, Department of Nuclear Medicine, Jacobi
Medical Center, New York, NY, USA
Dia Shehab, MD, FRCPC Professor, Department of Medicine,
Faculty of Medicine, Kuwait University, Kuwait City, Kuwait
Contributors xxi

Pravin C. Singhal, MD Director, Academic Affairs, Division of Kidney

Diseases and Hypertension, Hofstra Norh Shore LIJ Medical School,
Great Neck, NY, USA
Shankar Vallabhajosula, PhD Professor, Division of Nuclear Medicine,
Department of Radiology, New York Presbyterian Hospital,
Medical College of Cornell University, New York, NY, USA
Mohamad Zubaid, MD Professor, Department of Medicine,
Faculty of Medicine, Kuwait University, Kuwait City, Kuwait