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Radiology-Nuclear Medicine Diagnostic
Imaging: A Correlative Approach
Radiology-Nuclear Medicine Diagnostic
Imaging: A Correlative Approach

Edited by

Ali Gholamrezanezhad, MD
Associate Professor of Clinical Radiology, Keck School of Medicine
Universityof Southern California
Los Angeles, CA, USA

Majid Assadi, MD, MSc

Professor, Department of Radiology, School of Medicine
Director, Nuclear Medicine and Molecular Imaging Research Center
Bushehr University of Medical Sciences
Bushehr, Iran

Hossein Jadvar, MD, PhD, MPH, MBA

Professor of Radiology, Urology, and Biomedical Engineering
Keck School of Medicine and Viterbi School of Engineering
University of Southern California
Los Angeles, CA, USA
This edition first published 2023
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Library of Congress Cataloging-in-Publication Data applied for

ISBN: 9781119603610 (hardback)

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Set in 9.5/12.5pt STIXTwoText by Straive, Pondicherry, India

Dedicated to Mojgan, Donya, and Delara, with love. . .
Hossein Jadvar

To my family especially my mother, Maryam, my wife, Moloud, my sons, Arian and Aiden. For their endless sacrifices they
have made to make my life most rewarding
Majid Assadi

To those contributed to my education and excellence, especially my mother (the best teacher I have ever had), Fatemeh, my
brother, Hadi, my wife, Farzaneh, and my son, Adrian

and

To my patients, those who I served with the deepest gratitude and appreciation.
Ali Gholamrezanezhad
 vii

Contents

List of Contributors x
Preface xvii

1 Introduction to Correlative Imaging: What Radiologists and Nuclear Medicine Physicians Should
Know on Hybrid Imaging 1
Prathamesh V. Joshi, Alok Pawaskar, and Sandip Basu

2 Basic Principles of Hybrid Imaging 30

Leda Lorenzon, M. Bonelli, A. Fracchetti, and P. Ferrari

3 Cross-sectional Correlate for Integrative Imaging (Anatomical Radiology) 52

Antonio Jesús Láinez Ramos-Bossini, Ángela Salmerón-Ruiz, José Pablo Martínez Barbero, José Pablo
Martín Molina, José Luis Martín Rodríguez, Genaro López Milena, and Fernando Ruiz Santiago

4 Radiopharmaceuticals 133
Ferdinando Calabria, Mario Leporace, Rosanna Tavolaro, and Antonio Bagnato

5 Diseases of the Central Nervous System 163

Hiroshi Matsuda, Eku Shimosegawa, Yoko Shigemoto, Noriko Sato, Hiroyuki Fujii, Fumio Suzuki,
Yukio Kimura, and Atsuhiko Sugiyama

6 PET Imaging in Gliomas: Clinical Principles and Synergies with MRI 194
Riccardo Laudicella, C. Mantarro, B. Catalfamo, P. Alongi, M. Gaeta, F. Minutoli, S. Baldari, and Sotirios Bisdas

7 Diseases of the Head and Neck 219

Florian Dammann and Jan Wartenberg

8 The Role of Noninvasive Cardiac Imaging in the Management of Diseases

of the Cardiovascular System 257
Ahmed Aljizeeri and Mouaz H. Al-Mallah

9 Vascular System 285

Ahmad Shariftabrizi, Khalid Balawi, and Janet H. Pollard

10 Diseases of the Pulmonary System 308

Murat Fani Bozkurt and Bilge Volkan-Salanci

11 Thoracic Malignancies 333

Sanaz Katal, Thomas G. Clifford, Kanhaiyalal Agrawal, and Ali Gholamrezanezhad
viii Contents

12 A Correlative Approach to Breast Imaging 351

Shabnam Mortazavi, Sonya Khan, Kathleen Ruchalski, Cory Daignault, and Jerry W. Froelich

13 Correlative Imaging of Benign Gastrointestinal Disorders 383

Mariano Grosso, Michela Gabelloni, Emanuele Neri, and Giuliano Mariani

14 Gastrointestinal Malignancies 407

Janet H. Pollard, Paul A. DiCamillo, Ayca Dundar, Sarah L. Averill, and Yashant Aswani

15 Hepatobiliary Imaging 456

Janet H. Pollard

16 Correlative Imaging in Endocrine Diseases 485

Sana Salehi, Farshad Moradi, Doina Piciu, Hojjat Ahmadzadehfar, and Ali Gholamrezanezhad

17 Correlative Imaging in Neuroendocrine Tumors 512

Ameya Puranik, Sonal Prasad, Indraja D. Devi, and Vikas Prasad

18 Nephro-urinary Tract Pathologies: A Correlative Imaging Approach 521

Salar Tofighi, Thomas G. Clifford, Saum Ghodoussipour, Peter Henry Joyce, Meisam Hoseinyazdi, Maryam Abdinejad,
Saeideh Najafi, Fahad Marafi, and Russell H. Morgan

19 Correlative Approach to Prostate Imaging 533

Soheil Kooraki and Hossein Jadvar

20 Correlative Imaging of the Female Reproductive System 554

Sanaz Katal, Akram Al-Ibraheem, Fawzi Abuhijla, Ahmad Abdlkadir, Liesl Eibschutz, and Ali Gholamrezanezhad

21 Musculoskeletal Imaging 577

George R. Matcuk, Jr., Jordan S. Gross, Dakshesh B. Patel, Brandon K. K. Fields, Dorian M. Lapalma, and Daniel Stahl

22 Spine Disorders: Correlative Imaging Approach 625

Azadeh Eslambolchi, Amit Gupta, Jay Acharya, Christopher Lee, and Kaustav Bera

23 Osteoporosis: Diagnostic Imaging and Value of Multimodality Approach in Differentiating Benign Versus
Pathologic Compression Fractures 659
Daniela Garcia, Shambo Guha Roy, and Reza Hayeri

24 Emergency Radiology 671

Sean K. Johnston, Russell Flato, Peter Hu, Peter Henry Joyce, and Andrew Chong

25 Correlative Imaging of Pediatric Diseases 693

Seth J. Crapp, Rachel Pevsner Crum, Nolan Altman, Jyotsna Kochiyil, Eshani Sheth, and Caldon J. Esdaille

26 Infection/Inflammation Imaging 717

Christopher J. Palestro and Charito Love

27 Imaging the Lymphatic System 747

Girolamo Tartaglione, Marco Pagan, Francesco Pio Ieria, Giuseppe Visconti, and Tommaso Tartaglione

28 Lymphoma and Myeloma Correlative Imaging 772

Pavel Gelezhe, Sergey Morozov, Anton Kondakov, and Mikhail Beregov
 Contents ix

29 Clinical Application of PET/MRI 788

Laura Evangelista, Paolo Artoli, Paola Bartoletti, Antonio Bignotto, Federica Menegatti, Marco Frigo,
Stefania Antonia Sperti, Laura Vendramin, and Diego Cecchin

68
30 Ga-FAPI, a Twin Tracer for 18F-FDG in the Era of Evolving PET Imaging 814
Reyhaneh Manafi-Farid, GhasemAli Divband, HamidReza Amini, Thomas G. Clifford, Ali Gholamrezanezhad,
Mykol Larvie, and Majid Assadi

31 Artificial Intelligence in Diagnostic Imaging 826

Martina Sollini, Daniele Loiacono, Daria Volpe, Alessandro Giaj Levra, Elettra Lomeo, Edoardo Giacomello,
Margarita Kirienko, Arturo Chiti, and Pierluca Lanzi

32 Radionuclide Therapies and Correlative Imaging 838

Ashwin Singh Parihar and Erik Mittra

Index 871
x

List of Contributors

Maryam Abdinejad P. Alongi

Department of Radiology, Namazi Hospital, Shiraz, Iran
Department of Nuclear Medicine, Namazi Hospital,
Shiraz, Iran
Ahmad Abdlkadir
Department of Nuclear Medicine, King Hussein Cancer
Center, Amman, Jordan
Fawzi Abuhijla
Department of Radiation Oncology, King Hussein Cancer
Center, Amman, Jordan
Jay Acharya
Radiology, Keck School of Medicine of USC, HCCII Lower
Level Radiology, Los Angeles, CA, USA
Kanhaiyalal Agrawal
Department of Nuclear Medicine, All India Institute of
Medical Sciences, Bhubaneswar, India
Unit of Nuclear Medicine, Fondazione Istituto G. Giglio,
Cefalù, Italy
Nolan Altman
Nicklaus Children’s Hospital, Miami, FL, USA
HamidReza Amini
Khatam PET-CT Center, Khatam Hospital, Tehran, Iran
Paolo Artoli
Nuclear Medicine Unit, Department of Medicine,
University of Padua, Padua, Italy
Majid Assadi
Department of Radiology, School of Medicine, Nuclear
Medicine and Molecular Imaging Research Center
Bushehr University of Medical Sciences
Bushehr, Iran

Hojjat Ahmadzadehfar Yashant Aswani

Department of Nuclear Medicine, Klinikum Westfalen, University of Iowa, Carver College of Medicine, Iowa City,
Dortmund, Germany IA, USA

Akram Al-Ibraheem
Sarah L. Averill
Department of Nuclear Medicine, King Hussein Cancer
University of Iowa, Carver College of Medicine,
Center, Amman, Jordan
Iowa City, IA, USA
Iowa City Veterans Administration Healthcare System,
Ahmed Aljizeeri
Iowa City, IA, USA
King Abdulaziz Cardiac Center, Riyadh, Saudi Arabia
King Saud bin Abdulaziz University for Health Sciences,
Riyadh, Saudi Arabia Antonio Bagnato
King Abdullah International Medical Research Center, Department of Nuclear Medicine and Theranostics,
Riyadh, Saudi Arabia “Mariano Santo” Hospital, Cosenza, Italy

Mouaz H. Al-Mallah Khalid Balawi

Houston Methodist DeBakey Heart & Vascular Center, University of Iowa Carver College of Medicine,
Houston Methodist Hospital, Houston, TX, USA Iowa City, IA, USA
 List of Contributors xi

S. Baldari B. Catalfamo
Department of Biomedical Sciences and Morphological Department of Biomedical Sciences and Morphological
and Functional Imaging, Nuclear Medicine Unit, and Functional Imaging, Nuclear Medicine Unit,
University of Messina, Messina, Italy University of Messina, Messina, Italy

José Pablo Martínez Barbero Diego Cecchin

Department of Radiology, Virgen de las Nieves University Nuclear Medicine Unit, Department of Medicine,
Hospital, University of Granada, Granada, Spain University of Padua, Padua, Italy

Paola Bartoletti Arturo Chiti

Nuclear Medicine Unit, Department of Medicine, Department of Biomedical Sciences, Humanitas
University of Padua, Padua, Italy University, Milan, Italy
IRCCS Humanitas Research Hospital, Milan, Italy
Sandip Basu
Radiation Medicine Centre, Bhabha Atomic Research
Andrew Chong
Centre, Tata Memorial Centre Annexe, Parel, Mumbai,
Department of Radiology, Keck School of Medicine,
Maharashtra, India
University of Southern California, Los Angeles, CA, USA
Homi Bhabha National Institute, Mumbai,
Maharashtra, India
Thomas G. Clifford
Department of Radiology, Keck School of Medicine,
Kaustav Bera
University of Southern California, Los Angeles, CA, USA
Case Western Reserve University School of Medicine,
University Hospital Cleveland Medical Center,
Cleveland, OH, USA Seth J. Crapp
Pediatric Teleradiology Partners, Miami, FL, USA
Mikhail Beregov
Federal Center for Cerebrovascular Pathology and Stroke, Rachel Pevsner Crum
Department of Radiology and Functional Diagnostics, Nicklaus Children’s Hospital, Miami, FL, USA
Moscow, Russia
Cory Daignault
Antonio Bignotto Minneapolis VA Medical Center, Minneapolis, MN, USA
Nuclear Medicine Unit, Department of Medicine,
University of Padua, Padua, Italy
Florian Dammann
Department of Diagnostic, Interventional and Pediatric
Sotirios Bisdas
Radiology, Inselspital, University Hospital Bern,
Department of Brain Repair and Rehabilitation, UCL
Switzerland
Queen Square Institute of Neurology, University College
London, London, UK
Lysholm Department of Neuroradiology, Indraja D. Devi
The National Hospital for Neurology and Neurosurgery, Department of Nuclear Medicine, Tata Memorial
UCLH NHS Foundation Trust, Hospital, Homi Bhabha National Institute (HBNI),
London, UK Mumbai, Maharashtra, India

M. Bonelli Paul A. DiCamillo

Department of Medical Physics, Central Hospital of University of Iowa, Carver College of Medicine, Iowa City,
Bolzano, Bolzano, Italy IA, USA

Ferdinando Calabria GhasemAli Divband

Department of Nuclear Medicine and Theranostics, Nuclear Medicine Center, Jam Hospital, Tehran, Iran
“Mariano Santo” Hospital, Khatam PET-CT Center, Khatam Hospital,
Cosenza, Italy Tehran, Iran
xii List of Contributors

Ayca Dundar Michela Gabelloni

University of Iowa, Carver College of Medicine, Iowa City,
IA, USA
Liesl Eibschutz
Department of Radiology, Keck School of Medicine,
University of Southern California, Los Angeles, CA, USA
Caldon J. Esdaille
Howard University College of Medicine,
Washington, DC, USA
Azadeh Eslambolchi
Pediatric Radiology Section, Mallinckrodt Institute of
Radiology, Washington University in St Louis, School of
Medicine, St. Louis, MO, USA
Laura Evangelista
Nuclear Medicine Unit, Department of Medicine,
University of Padua, Padua, Italy
Diagnostic and Interventional Radiology, Department of
Translational Research and Advanced Technologies in
Medicine and Surgery, University of Pisa, Pisa, Italy
M. Gaeta
Section of Radiological Sciences, Department of
Biomedical Sciences and Morphological and Functional
Imaging, University of Messina, Messina, Italy
Daniela Garcia
Department of Radiology, Mercy Catholic Medical Center,
Darby, PA, USA
Pavel Gelezhe
Research and Practical Clinical Center for Diagnostics and
Telemedicine Technologies of the Moscow Health Care
Department, Moscow, Russia
European Medical Center, Radiology Department,
Moscow, Russia

Murat Fani Bozkurt
Department of Nuclear Medicine, Hacettepe University
Faculty of Medicine, Ankara, Turkey
P. Ferrari
Department of Medical Physics, Central Hospital of
Bolzano, Bolzano, Italy
Brandon K. K. Fields
Keck School of Medicine, University of Southern
California, Los Angeles, CA, USA
Russell Flato
Department of Radiology, Keck School of Medicine,
University of Southern California, Los Angeles, CA, USA
A. Fracchetti
Department of Medical Physics, Central Hospital of
Bolzano, Bolzano, Italy
Marco Frigo
Nuclear Medicine Unit, Department of Medicine,
University of Padua, Padua, Italy
Jerry W. Froelich
Radiology, University of Minnesota, Minneapolis, MN, USA
Hiroyuki Fujii
Department of Radiology, National Center of Neurology
and Psychiatry, Kodaira, Japan
Saum Ghodoussipour
Rutgers Robert Wood Johnson Medical School, New
Brunswick, NJ, USA
Section of Urologic Oncology, Rutgers Cancer Institute of
New Jersey, New Brunswick, NJ, USA
Ali Gholamrezanezhad
Department of Radiology, Keck School of Medicine,
University of Southern California, Los Angeles, CA, USA
Edoardo Giacomello
Dipartimento di Elettronica, Informazione e
Bioingegneria, Politecnico di Milano, Milano, Italy
Jordan S. Gross
Department of Radiology, University of California, Los
Angeles, Los Angeles, CA, USA
Mariano Grosso
Regional Center of Nuclear Medicine, Department of
Translational Research and Advanced Technologies in
Medicine and Surgery, University of Pisa, Pisa, Italy
Amit Gupta
Radiology, Medicine and Biomedical Engineering,
Case Western Reserve University School of Medicine,
Cleveland, OH, USA
Cancer Imaging Program, Case Comprehensive Cancer
Center, Cleveland, OH, USA
Diagnostic Radiography, University Hospital Cleveland
Medical Center, Cleveland, OH, USA

Reza Hayeri
Department of Radiology, Mercy Catholic Medical Center,
Darby, PA, USA
Meisam Hoseinyazdi
Shiraz University of Medical Sciences, Shiraz, Iran
Department of Radiology, Namazi Hospital, Shiraz, Iran
Peter Hu
Department of Radiology, Keck School of Medicine,
University of Southern California, Los Angeles, CA, USA
Hossein Jadvar
Professor of Radiology, Urology, and Biomedical
Engineering, Keck School of Medicine and Viterbi School
of Engineering, University of Southern California, Los
Angeles, CA, USA
Sean K. Johnston
Department of Radiology, Division of Emergency
Radiology, Keck School of Medicine of USC, LAC+USC
Medical Center, Los Angeles, CA, USA
Prathamesh V. Joshi
Department of Nuclear Medicine & PET-CT,
Kamalnayan Bajaj Hospital, Aurangabad,
Maharashtra, India
Radiation Medicine Centre, Bhabha Atomic Research
Centre, Tata Memorial Centre Annexe, Parel, Mumbai,
Maharashtra, India
Peter Henry Joyce
Department of Radiology, Keck School of Medicine,
University of Southern California, Los Angeles, CA, USA
Sanaz Katal
Nuclear Medicine Fellow, Medical Imaging Department,
St Vincent’s Hospital Melbourne, Australia
Sonya Khan
Los Angeles and Veterans Administration, Greater Los
Angeles Healthcare Systems, University of California, Los
Angeles, CA, USA
Yukio Kimura
Department of Radiology, National Center of Neurology
and Psychiatry, Kodaira, Japan
Margarita Kirienko
Department of Nuclear Medicine, Istituto Nazionale per
lo Studio e la Cura dei Tumori, Milano, Italy
List of Contributors xiii
Jyotsna Kochiyil
Mount Sinai Medical Center, Miami Beach, FL, USA
Anton Kondakov
Central Clinical Hospital of the Russian Academy of
Sciences, Nuclear Medicine Department, Moscow, Russia
Pirogov Russian National Research Medical University,
Department of Radiology and Radiation Therapy,
Moscow, Russia
Soheil Kooraki
Department of Molecular and Medical Pharmacology,
David Geffen School of Medicine at UCLA, University of
California, Los Angeles, CA, USA
Pierluca Lanzi
Dipartimento di Elettronica, Informazione e
Bioingegneria, Politecnico di Milano, Milano, Italy
Dorian M. Lapalma
Department of Radiology, University of Southern
California, Los Angeles, CA, USA
Keck School of Medicine, University of Southern
California, Los Angeles, CA, USA
Mykol Larvie
Department of Radiology, Cleveland Clinic, Cleveland,
OH, USA
Riccardo Laudicella
Department of Biomedical Sciences and Morphological
and Functional Imaging, Nuclear Medicine Unit,
University of Messina, Messina, Italy
Christopher Lee
Keck School of Medicine of USC, HCCII Lower Level
Radiology, Los Angeles, CA, USA
Mario Leporace
Department of Nuclear Medicine and Theranostics,
“Mariano Santo” Hospital, Cosenza, Italy
Alessandro Giaj Levra
IRCCS Humanitas Research Hospital, Milan, Italy
Daniele Loiacono
Dipartimento di Elettronica, Informazione e
Bioingegneria, Politecnico di Milano, Milano, Italy
Elettra Lomeo
IRCCS Humanitas Research Hospital,
Milan, Italy
xiv List of Contributors
Leda Lorenzon
Department of Medical Physics, Central Hospital of
Bolzano, Bolzano, Italy
Charito Love
Radiology, Albert Einstein College of Medicine,
Bronx, NY, USA
Reyhaneh Manafi-Farid
Research Center for Nuclear Medicine, Shariati Hospital,
Tehran University of Medical Sciences,
Tehran, Iran
C. Mantarro
Department of Biomedical Sciences and Morphological
and Functional Imaging, Nuclear Medicine Unit,
University of Messina, Messina, Italy
Fahad Marafi
Jaber Al-Ahmad Center for Molecular Imaging, Kuwait
City, Kuwait
Giuliano Mariani
Regional Center of Nuclear Medicine, Department of
Translational Research and Advanced Technologies in
Medicine and Surgery, University of Pisa, Pisa, Italy
José Pablo Martín Molina
Department of Radiology, San Cecilio University Hospital,
University of Granada, Granada, Spain
George R. Matcuk, Jr.
Department of Imaging, Cedars-Sinai Medical Center, Los
Angeles, CA, USA
Hiroshi Matsuda
Integrative Brain Imaging Center, National Center of
Neurology and Psychiatry, Kodaira, Japan
Federica Menegatti
Nuclear Medicine Unit, Department of Medicine,
University of Padua, Padua, Italy
Genaro López Milena
Department of Radiology, Virgen de las Nieves University
Hospital, University of Granada, Granada, Spain
F. Minutoli
Department of Biomedical Sciences and Morphological
and Functional Imaging, Nuclear Medicine Unit,
University of Messina, Messina, Italy
Erik Mittra
Department of Diagnostic Radiology, Division of Nuclear
Medicine & Molecular Imaging, Oregon Health & Science
University, Portland, OR, USA
Farshad Moradi
Department of Radiology, Division of Nuclear Medicine,
Stanford, CA, USA
Russell H. Morgan
Department of Radiology and Radiological Science, Johns
Hopkins Medical Institution, Baltimore, MD, USA
Sergey Morozov
Chief innovation officer, Osimis S.A., Belgium
Shabnam Mortazavi
Radiology, David Geffen School of Medicine at UCLA,
Los Angeles, CA, USA
Saeideh Najafi
Department of Radiology, Keck School of Medicine,
University of Southern California, Los Angeles, CA, USA
Emanuele Neri
Diagnostic and Interventional Radiology, Department
of Translational Research and Advanced Technologies
in Medicine and Surgery, University of Pisa,
Pisa, Italy
Marco Pagan
Nuclear Medicine, Cristo Re Hospital, Rome, Italy
Christopher J. Palestro
Radiology, Donald & Barbara Zucker School of Medicine
at Hofstra/Northwell, Hempstead, NY, USA
Nuclear Medicine & Molecular Imaging, Northwell
Health, New Hyde Park, NY, USA
Ashwin Singh Parihar
Department of Nuclear Medicine, Postgraduate Institute
of Medical Education and Research, Chandigarh, India
Mallinckrodt Institute of Radiology, Washington
University School of Medicine, St Louis, MO, USA
Dakshesh B. Patel
Department of Radiology, University of Southern
California, Los Angeles, CA, USA
Keck School of Medicine, University of Southern
California, Los Angeles, CA, USA

Alok Pawaskar
Radiation Medicine Centre, Bhabha Atomic Research
Centre, Tata Memorial Centre Annexe, Parel, Mumbai,
Maharashtra, India
Department of Nuclear Medicine & PET-CT,
Shri Siddhivinayak Ganapati Cancer Hospital, Miraj,
Maharashtra, India
Doina Piciu
Department of Endocrine Tumors and Nuclear Medicine,
Institute of Oncology Ion Chiricuta and University of
Medicine Iuliu Hatieganu, Cluj-Napoca, Romania
Francesco Pio Ieria
Nuclear Medicine, Cristo Re Hospital, Rome, Italy
Janet H. Pollard
University of Iowa Carver College of Medicine,
Iowa City, IA, USA
Sonal Prasad
Berlin Experimental Radionuclide Imaging Center, Berlin,
Germany
Department of Nuclear Medicine, Charité-
Universitaetsmedizin, Berlin, Germany
Vikas Prasad
Department of Nuclear Medicine, University Hospital,
Ulm, Germany
Ameya Puranik
Department of Nuclear Medicine, Tata Memorial
Hospital, Homi Bhabha National Institute (HBNI),
Mumbai, Maharashtra, India
Antonio Jesús Láinez Ramos-Bossini
Department of Radiology, Virgen de las Nieves University
Hospital, University of Granada, Granada, Spain
José Luis Martín Rodríguez
Department of Radiology, San Cecilio University Hospital,
University of Granada, Granada, Spain
Shambo Guha Roy
Department of Radiology, Mercy Catholic Medical Center,
Darby, PA, USA
Kathleen Ruchalski
Radiology, David Geffen School of Medicine at UCLA,
Los Angeles, CA, USA
Sana Salehi
Department of Radiology, Keck School of Medicine,
University of Southern California, Los Angeles, CA, USA
List of Contributors xv
Ángela Salmerón-Ruiz
Department of Radiology, Virgen de las Nieves University
Hospital, University of Granada, Granada, Spain
Fernando Ruiz Santiago
Department of Radiology, Virgen de las Nieves University
Hospital, University of Granada, Granada, Spain
Neuro-traumatology Hospital, Virgen de las Nieves
University Hospital, School of Medicine, University of
Granada, Granada, Spain
Noriko Sato
Department of Radiology, National Center of Neurology
and Psychiatry, Kodaira, Japan
Ahmad Shariftabrizi
University of Iowa Carver College of Medicine,
Iowa City, IA, USA
Veterans Affair Medical Center, Iowa City, IA, USA
Eshani Sheth
Mount Sinai Medical Center, Miami Beach, FL, USA
Yoko Shigemoto
Department of Radiology, National Center of Neurology
and Psychiatry, Kodaira, Japan
Eku Shimosegawa
Department of Molecular Imaging in Medicine, Osaka
University Graduate School of Medicine, Suita, Japan
Martina Sollini
Department of Biomedical Sciences, Humanitas
University, Milan, Italy
IRCCS Humanitas Research Hospital, Milan, Italy
Stefania Antonia Sperti
Nuclear Medicine Unit, Department of Medicine,
University of Padua, Padua, Italy
Daniel Stahl
Keck School of Medicine, University of Southern
California, Los Angeles, CA, USA
Atsuhiko Sugiyama
Department of Neurology, Graduate School of Medicine,
Chiba University, Chiba, Japan
Fumio Suzuki
Department of Radiology, National Center of Neurology
and Psychiatry, Kodaira, Japan
Girolamo Tartaglione
Nuclear Medicine, Cristo Re Hospital, Rome, Italy
xvi List of Contributors
Tommaso Tartaglione
Radiology, IDI-IRCCS, Rome, Italy
Rosanna Tavolaro
Department of Nuclear Medicine and Theranostics,
“Mariano Santo” Hospital, Cosenza, Italy
Salar Tofighi
Department of Radiology, Keck School of Medicine,
University of Southern California, Los Angeles, CA, USA
Laura Vendramin
Nuclear Medicine Unit, Department of Medicine,
University of Padua, Padua, Italy
Giuseppe Visconti
Plastic Surgery, Lymphedema Center, A. Gemelli Hospital,
Sacro Cuore Catholic University, Rome, Italy
Bilge Volkan-Salanci
Department of Nuclear Medicine, Hacettepe University
Faculty of Medicine, Ankara, Turkey
Daria Volpe
Department of Biomedical Sciences, Humanitas
University, Milan, Italy
IRCCS Humanitas Research Hospital,
Milan, Italy
Jan Wartenberg
Department of Nuclear Medicine, Inselspital,
University Hospital Bern, Switzerland

Preface
Medical imaging has come a long way since the discovery
of X-rays by Wilhelm Rontgen, for which he received the
Nobel Prize in 1901. For over a century, medical imaging
has evolved remarkably with discoveries and the develop-
ment of innovative technologies which in combination
with major strides in understanding the biology of health
and disease have contributed significantly to the concept of
precision health and precision medicine. These milestones
include, but are not limited to, the discovery of radioactiv-
ity and positron and technical developments of the radi-
otracer concept, cyclotron, computed tomography (CT),
ultrasonography (US), magnetic resonance imaging (MRI),
single photon computed tomography (SPECT), and posi-
tron emission tomography (PET). Advances in computer
technology have also provided opportunities for sophisti-
cated incorporation of radiomics, artificial intelligence,
and deep learning (AI/DL) algorithms in medical imaging.
Over the past decade, it has become clear that hybrid imag-
ing (e.g. PET/CT, PET/MRI, SPECT/CT) provides a broader
view of disease that was unavailable previously. For exam-
ple, it is now recognized that a small lymph node may har-
bor a tumor while a large lymph node may be benign.
Another example is visualization of tumor infiltration in
marrow space without concordant structural abnormali-
ties. Such comprehensive information provides opportuni-
ties for enhanced imaging assessment of the patient, which
has been demonstrated to impact clinical management and
improve patient outcome.
The editors of this book have assembled an international
team of expert imaging specialists to compile comprehen-
sive coverage of correlative imaging in the domains of
xvii
diagnostic radiology and nuclear medicine, addressing all
major organ systems and major diseases (cardiovascular,
neurologic, oncologic, infection, and inflammation, in
both adults and children). In all chapters, there is emphasis
on correlative imaging and how one imaging modality
complements another in a synergistic way. As appropriate,
the reader is introduced to the relevant anatomy and physi-
ology. Modern topics of radiomics, AI/DL, and theranos-
tics are discussed. This image-rich book will appeal to
physicians, allied healthcare professionals, and trainees
(medical students, residents, fellows). The editors regret
any potential errors and omissions and commit to remedy
any shortcomings in any future editions.
We dedicate this book to the memory of Sanjiv “Sam”
Gambhir, MD, PhD, Chair of Radiology at Stanford
University. Sam was our mentor, friend, and colleague. He
was larger than life with deep intellect, contagious gener-
osity, and remarkable humility. The entire scientific com-
munity and indeed humanity itself lost a glorious soul
from his untimely passing in July 2020.
Ali Gholamrezanezhad
Clinical Radiology, University of Southern California,
Los Angeles, CA, USA
Majid Assadi
Nuclear Medicine, Bushehr University of Medical
Sciences, Bushehr, Iran
Hossein Jadvar
Radiology, Urology, and Biomedical Engineering,
University of Southern California, Los Angeles, CA, USA

Introduction to Correlative Imaging
What Radiologists and Nuclear Medicine Physicians Should Know on Hybrid Imaging
Prathamesh V. Joshi1,2, Alok Pawaskar 2,3, and Sandip Basu2,4
1
Department of Nuclear Medicine & PET-CT, Kamalnayan Bajaj Hospital, Aurangabad, Maharashtra, India
2
Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Centre Annexe, Parel, Mumbai, Maharashtra, India
3
Department of Nuclear Medicine & PET-CT, Shri Siddhivinayak Ganapati Cancer Hospital, Miraj, Maharashtra, India
4
Homi Bhabha National Institute, Mumbai, Maharashtra, India
Introduction
Correlation is defined as a connection or relationship
between two or more things that are not caused by
chance [1]. Medical research is naturally based on finding
the relationship between the known and the unknown [2].
Correlation has been an integral part of medicine. A clini-
cian correlates signs and symptoms with the results of
medical imaging, pathology or laboratory investigations.
A nuclear medicine physician or radiologist correlates
findings of medical imaging with another imaging modal-
ity or laboratory investigation such as tumor marker levels,
hormone levels etc. Correlative imaging comprises com-
bining complimentary information provided by different
imaging techniques for better interpretation of pathology.
In this chapter, our aim is to familiarize readers with the
basics of correlative imaging, the strengths and shortcom-
ings of various imaging modalities, and how the correla-
tion among them leads to better understanding of
pathologies. The main emphasis of this chapter will be on
“fusion imaging”, which has proved to be the best available
form of correlative imaging at present.
Correlative Imaging
Medical imaging has come a long way since Roentgen first
discovered the X-ray in 1895 [3]. Today X-ray, fluoroscopy,
computed tomography (CT), ultrasonograpy, single-photon
emission tomography (SPECT), positron emission tomog-
raphy (PET), magnetic resonance imaging (MRI), PET-CT,
SPECT-CT, and PET-MRI form the gamut of medical
Radiology-Nuclear Medicine Diagnostic Imaging: A Correlative Approach, First Edition. Edited by Ali Gholamrezanezhad,
Majid Assadi, and Hossein Jadvar.
© 2023 John Wiley & Sons Ltd. Published 2023 by John Wiley & Sons Ltd.
1
imaging. Table 1.1 provides a brief review of the different
tomographic imaging modalities which form the crux of
correlative imaging.
Each imaging modality has its own strengths and short-
comings. The utilization of an individual modality depends
on multiple factors:
1) Patient-related factors: age of patient, organ of interest,
claustrophobia, contrast allergy, pregnancy etc.
2) Modality-related factors: availability, radiation expo-
sure, resolution, need of morphological versus func-
tional information
3) Physician-related factors: expertise of radiologist/
nuclear medicine physician or preference of referring
physician
4) Miscellaneous: financial burden of examination, insur-
ance coverage etc.
Depending on these multiple factors, an imaging modal-
ity is utilized as the investigation of choice during workup
of a particular patient. However, it is not uncommon that
imaging findings are nonspecific and rather than leading to
a definitive diagnosis they lead to a spectrum of differential
diagnoses. Through “fusion imaging” or “hybrid imaging”
radiologists/nuclear physicians frequently utilize correla-
tive imaging with the intent to narrow down the differentials
and/or pinpoint the diagnosis.
Correlative imaging can be defined as “imaging the
same sample (field of view [FOV] or subject)
sequentially or simultaneously with different imag-
ing modalities to obtain complimentary/additive
information.”
2 Radiology-Nuclear Medicine Diagnostic Imaging: A Correlative Approach

Table 1.1 Overview of the salient attributes of important tomographic imaging modalities.

PET SPECT CT MRI

Principle Three-dimensional Computer-generated image of local Combined X-ray Strong magnetic field
distribution of radioactive tracer distribution in transmission source and radio waves to
positron-emitting tissues produced through the detection and detector system create detailed
labeled radiotracers of single-photon emissions from rotating around the images of the organs
radionuclides introduced into the body subject to generate and tissues within
in the form of SPECT radiotracers tomographic images the body
The tracer/ Positron-emitting Gamma-ray-emitting Iodine-containing Gadolinium-based
contrast used radio-pharmaceuticals radio-pharmaceuticals contrast medium contrast agents
Resolution ++ + +++ +++
Functional +++ ++ + ++
assessment
Radiation ++ + +++ None
exposure
Allergy/acute No No Yes Yes
side effects
Measurable PET tracer − Attenuation value/ Apparent diffusion
parameter/ uptake/standardized Hounsfield unit coefficient/mm2/s
quantification uptake value
unit

CT, computed tomography; MRI, magnetic resonance imaging; PET, positron emission tomography; SPECT, single-photon emission
tomography.

Correlative imaging has been in practice in the form of
comparative imaging for many years, a typical example of
this being the “hot spot” observed in bone scans interpreted
as metastatic or degenerative based on comparing it with
MRI or CT of the same bone. However, now fusion imaging
techniques such as SPECT-CT, PET-CT, and PET-MRI have
emerged as most widely accepted form of correlative imag-
ing. Conventionally, SPECT and PET had been domains of
nuclear physicians while CT and MR had been the radiolo-
gist’s forte. With the advent and rapid success of fusion
imaging there is a need for combined knowledge of both
nuclear medicine and radiology for accurate interpretation
of fusion imaging findings. In the next section, we aim to
familiarize nuclear physicians and radiologists with the
basic principles of tomographic techniques utilized in
correlative/fusion imaging.
Positron Emission Tomography–Computed
Tomography
PET-CT: What a Radiologist Should Know about PET
Basics of PET-CT
Positron Emission Tomography
PET is a tomographic technique that measures the three-
dimensional distribution of positron-emitter labeled radi-
otracers. PET allows noninvasive quantitative assessment of
biochemical and functional processes. The most commonly
used tracer at present is the 18F-labeled glucose analogue
fluorodeoxyglucose (FDG), and it is the workhorse of
PET-CT imaging at present.
Though most commonly utilized in oncological imaging,
FDG-PET has many other nononcological applications
now: dementia, myocardial viability, and infection imaging
to name a few. Hence FDG is utilized here as example to
demonstrate PET tracer characteristics to radiologists.
● Principle of FDG PET imaging
Enhanced glucose metabolism of cancer cells (primarily
dependent on anaerobic glycolysis or the Warburg effect)
forms the fundamental basis of FDG PET/CT imaging of
malignancies. The increased glucose utilization by the
malignant cells is characterized by high expression of glu-
cose transporters (GLUTs, namely GLUT1 and GLUT3)
and upregulation of hexokinase activity [4].
Glucose is taken up by tumor cells by facilitated transport
(via GLUT) and then undergoes glycolysis with the forma-
tion of pyruvate under aerobic conditions. However, under
hypoxic conditions (such as in a necrotic tumor), glucose is
metabolized under anaerobic conditions with resultant
increased tumor lactate levels. FDG is a radiopharmaceuti-
cal (RP) analog of glucose that is taken up by metabolically
active tumor cells using facilitated transport similar to that
used by glucose (Figure 1.1). Despite the chemical differ-
ences, cellular uptake of FDG is similar to that for glucose.
FDG passes the cellular membrane through facilitated
transport mediated by the GLUTs, of which more than 14

CELL
CYTOPLASM
hexokinase
GLUCOSE GLUCOSE
GLUT Glusose-6-
receptors
phosphatase
CELL
CYTOPLASM
hexokinase
F-18 FLUORODEOXYGLUCOSE FDG
(FDG)
GLUT Glusose-6-
receptors
phosphatase
Figure 1.1 Mechanism of FDG uptake and metabolic trapping inside the cell.
different isoforms have been identified in humans, differing
in their tissue distribution and affinity for glucose. GLUT1
is the most common glucose transporter in humans and is,
together with GLUT3, overexpressed in many tumors [5–7].
Like glucose, it undergoes phosphorylation to form FDG-6-
phosphate; however, unlike glucose, it does not undergo
further metabolism. At the same time, expression of the
enzyme glucose-6-phosphatase is usually significantly
decreased in the malignant cells, and FDG-6-phosphate
thus undergoes only minimal dephosphorylation, hence
becoming “metabolically trapped” in cancer cells [8]. The
distribution of FDG in normal organs and pathological
lesions is detected by PET scanners.
● Preparation for FDG-PET and scan acquisition
Patients are advised to fast and not consume beverages,
except for water, for at least 4–6 hours before the admin-
istration of FDG to decrease physiologic glucose levels
and to reduce serum insulin levels to near basal levels.
Oral hydration with water is encouraged. Intravenous
fluids containing dextrose or parenteral feedings also
should be withheld for 4–6 hours [9]. FDG is injected
intravenously and the PET scan is typically acquired
50–90 minutes after FDG injection.
● Normal biodistribution and physiological variants
Physiological FDG uptake is seen in the brain, myocar-
dium, liver, spleen, stomach, intestines, kidneys and
Introduction to Correlative Imaging 3
GLUCOSE-6-PO4
glycolysis
FDG-6-PO4
glycolysis
urine, lymphoid tissue, bone marrow, salivary glands,
and testes (Figure 1.2). Breast, uterus, ovary, and thymus
can show variable FDG uptake.
Causes of Physiological FDG Uptake and Normal
Variants Mimicking Pathology
As increased FDG uptake is not limited to malignant tis-
sues alone, for the appropriate interpretation of FDG
PET-CT imaging the interpreting radiologist needs to be
aware of the physiological causes of FDG uptake as well as
commonly encountered physiological variants [10–15].
Table 1.2 summarizes and enumerates the different
physiological causes and sites of FDG uptake that can
mimic disease and the suggested interventions to reduce
them.
● Quantification of FDG uptake and SUV
While interpreting a PET-CT scan, it is the relative tissue
uptake of FDG (or any other PET RP) that is of interest to
the reporting physician. Visual analysis is sufficient in
most cases, but the standardized uptake value (SUV) is a
commonly used measure of FDG uptake and it is routinely
mentioned in PET-CT reports. The basic expression for
SUV is [16]
r
SUV
a w
4 Radiology-Nuclear Medicine Diagnostic Imaging: A Correlative Approach

(a) (b)

Brain

Heart

Liver Spleen

Kidney

Bone marrow

Urinary
bladder

Testes

Figure 1.2 A typical example of the physiological distribution of FDG uptake in a conventional vertex-to-mid thigh whole-body PET
study. (a) Maximum intensity projection (MIP) image of a PET scan. (b) Three columns depicting (left to right) trans-axial PET only,
trans-axial CT only, and trans-axial fused PET-CT images of physiological distribution.

where r is the radioactivity activity concentration (kBq/ml)
measured by the PET scanner within a region of interest
(ROI), a is the decay-corrected amount of injected radiola-
beled FDG (kBq), and w is the weight of the patient (g),
which is used as a surrogate for distribution volume of
tracer. If all the injected FDG is retained and uniformly dis-
tributed throughout the body, the SUV everywhere will be
1 g/ml regardless of the amount of FDG injected or patient
size [17, 18]. Commonly SUVmax of lesions (maximum
SUV) is provided in reports, which is the SUV of most avid
voxel in ROI.
The reproducibility of SUV measurements depends on
the reproducibility of clinical protocols, for example dose
infiltration, time of imaging after 18F-FDG administration,
type of reconstruction algorithms, type of attenuation
maps, size of the ROI, and changes in uptake by organs
other than the tumor [9]. SUV or SUVmax values are often
utilized as a marker of change in the metabolic activity of
pathology and hence it is important to reproduce the scan
conditions during the follow-up PET-CT scan performed
for response evaluation.
What Nuclear Medicine Physicians Need
to Know about CT
PET alone is limited by poor anatomic detail, and correla-
tion with some other form of imaging, such as CT, is desir-
able for differentiating normal from abnormal radiotracer
uptake [8]. Hence PET-CT morpho-metabolic imaging
emerged as an ideal single investigation for oncology prac-
tice. However, this also mandates the nuclear physician to
have adequate knowledge of the CT component of imaging
as well as the various interventions employed in CT
acquisition.

Table 1.2 Characteristics and causes of physiological uptake of FDG and methods to circumvent them.
Causes/sites of
FDG uptake Physiology behind FDG uptake
Brown adipose Nonshivering thermogenesis
tissue (BAT) requires glucose for glycolysis as a
source of adenosine triphosphate,
which in turn is utilized in fatty
acid oxidation
BAT is innervated by the
sympathetic nervous system and
expresses beta-adrenergic receptors,
which are stimulated by cold
Vocal cords Phonation-related laryngeal muscle
contraction
Myocardium Glucose as substrate for energy
(GLUT1 and insulin-sensitive
GLUT4)
Thymus Physiological uptake in pediatric
patients (especially in
postchemotherapy setting, known
as “thymic rebound”)
Lactating Due to secretory hyperplasia and
breasts the increased expression of GLUT-1
Urinary system FDG excretion in urine
Ovary FDG uptake in corpus luteal cyst
Endometrium FDG in menstrual flow
Colon Related to bowel motility
The uptake in cecum and right
colon could be result of higher
lymphocytes in these regions
Introduction to Correlative Imaging
PET-CT appearance
FDG uptake in fat density
(−150 to −50 HU) in neck,
shoulder, and paraspinal regions
(Figure 1.3)
Less common in perirenal,
perigastric regions
FDG uptake in BAT is more
common in younger patients,
females > males
Symmetrically increased FDG
uptake in both vocal cords
(Figure 1.4)
Variable, focal or diffuse without
corresponding morphologic
abnormality on CT
Inverted V-shaped/butterfly pattern
of anterior mediastinal uptake on
the transaxial view and absence of
lesion on corresponding CT
(Figure 1.5)
Bilateral breast reveal diffuse FDG
uptake, but if infant is suckling
unilateral breast only that side can
show diffuse FDG uptake
(Figure 1.6)
Usually does not affect scan
interpretation
Focal retention in kidneys/ureter/
urinary bladder can mimic
pathology
Ovoid FDG uptake with smooth
margins or a rim of FDG uptake
with a photopenic center
(Figure 1.7)
FDG uptake in endometrium in a
diffuse uniform pattern
(Figure 1.8)
Typically heterogeneous and can
vary in distribution from mild focal
to diffuse uptake
Often, there is higher uptake
within the cecum and right colon
5
Interventions to reduce uptake
Making patients wear warm
clothing and providing a
blanket in the waiting suite
to avoid cold-induced BAT
activation.
Premedication with
beta-blockers or diazepam
If the region of interest is the
larynx, the patient should be
instructed to avoid talking
after FDG injection
Fasting before FDG PET-CT
(4–12 hours)
High-fat, low-carbohydrate
diet before scan
Premedication with
unfractionated heparin
before FDG injection
The uptake has a diffuse
characteristic pattern: no
specific intervention
The uptake has a diffuse
characteristic pattern: no
specific intervention
Dual point/delayed postvoid
imaging with or without
diuretic intervention
Correlation with menstrual
history
If being evaluated for
gynecological pathology,
PET-CT scan should be
scheduled in the
postmenstrual phase
Uptake pattern: no
interventions
(Continued)
6 Radiology-Nuclear Medicine Diagnostic Imaging: A Correlative Approach

Table 1.2 (Continued)

Causes/sites of
FDG uptake Physiology behind FDG uptake PET-CT appearance Interventions to reduce uptake

Spinal cord Inadequate clearance of FDG from
the artery of Adamkiewicz, which
originates on the left side of the
aorta between the T9 and T11
vertebral segments
Increased cross-sectional area of
the spinal cord
Skeletal Exercise induces glucose uptake in
muscles skeletal muscles
Labored breathing can increase
FDG uptake in intercostal muscles
and diaphragm
In postmeal state, insulin increases
GLUT (GLUT-4) mediated skeletal
muscle glucose uptake
The physiological FDG uptake is
visualized in the cervical spinal
cord peaking at C4 level, and in the
lower thoracic spinal cord peaking
at the T11–T12 segments
(Figure 1.9)
If related to exercise, usually Patients should avoid
symmetrical FDG uptake in strenuous exercise for
muscles with no abnormal 48–72 hours before
enhancement or lesion on CT scheduled scan
If related to meal/insulin diffuse Fasting status should be
FDG uptake in skeletal muscles confirmed before FDG
(usually also accompanied with injection
cardiac FDG uptake)
If related to labored breathing,
intercostal muscles and diaphragm
reveal symmetrical increased FDG
uptake (Figure 1.10)

BAT, brown adipose tissue; FDG, fluorodeoxyglucose; GLUT1, glucose transporter 1; GLUT4, glucose transporter 4; PET-CT, positron emission
tomography/computed tomography.

(a) (b)

(c)

(d)

Figure 1.3 (a) FDG uptake in brown adipose tissue in bilateral cervical (red arrows), paraspinal, and perirenal regions as shown in
MIP image, (b) transaxial PET-only image of the neck region, (c) transaxial CT-only image, and (d) fused PET-CT image.

(a) (b)
Figure 1.4 (a) Transaxial CT-only image of vocal cords. (b) The fused PET-CT image of the same region shows symmetrical increased
FDG uptake in bilateral vocal cords (arrows). This patient was groaning due to painful skeletal secondaries, resulting in
hypermetabolism in the vocal cords.
(a) (b)
Figure 1.5 (a) MIP image of PET-CT of a 10-year-old boy
showing physiological FDG uptake in the thymus (black arrows).
(b) Hypermetabolism in the soft tissue neoplasm in the occipital
region (red arrow).
Computed Tomography
Although the potential applications of X-rays in medical
imaging diagnosis were clear from the beginning, the
implementation of the first X-ray CT system was made in
1972 by Godfrey Newbold Hounsfield (Nobel prize winner
in 1979 for Physiology and Medicine), who constructed the
prototype of the first medical CT scanner and is considered
the father of CT. After this, CT was immediately welcomed
by the medical community and has often been referred to
Introduction to Correlative Imaging 7
as the most important invention in radiological diagnosis
since the discovery of X-rays [19, 20].
Principle of CT
The CT scanner creates cross-sectional images by project-
ing a beam of X-rays through one plane of an object
(patient) from defined angle positions performing one rev-
olution. These X-rays are generated by a rotating X-ray tube
(Figure 1.11). As the X-rays pass through the patient‚ some
of them are absorbed, while some are scattered and others
are transmitted. The process of X-ray attenuation refers to
the intensity reduction involving those X-rays which are
scattered or absorbed. X-rays which are attenuated due to
the interactions with the object do not reach the X-ray
detector. Photons transmitted through the object at each
angle are collected on the detector and visualized by com-
puter, creating a complete reconstruction of the patient.
The three-dimensional (3D) gray value data structure
gained in this way represents the electron density distribu-
tion in the area of interest [19].
The ability of matter to attenuate X-rays is measured in
Hounsfield units (HU). By definition, water is assigned a
density value of 0 HU and air a value of −1000 HU.
Attenuation values for most soft tissues fall within
30–100 HU. Notable exceptions are lungs, with attenuation
values approaching −1000 HU (due to high air content),
and mineralized tissues such as bone, with attenuation val-
ues of approximately 1000 HU [21].
Intravenous and Oral Contrast in CT Scanning
Intravenous Contrast
Differences in the CT attenuation of healthy tissue
and pathology can improve the quality of the images
8 Radiology-Nuclear Medicine Diagnostic Imaging: A Correlative Approach

(a) (b)

(c)

(d)

Figure 1.6 (a) MIP image of PET-CT showing FDG uptake in bilateral breasts of a nursing mother (red arrows), (b) transaxial FDG PET
of breast region, (c) CT of breast region and (d) fused PET-CT of breast region.

(a) (b)

Figure 1.7 (a) CT image of pelvic region and (b) fused PET-CT of same region showing increased FDG uptake in a corpus luteal cyst in
the left adnexal region (arrow).
 Introduction to Correlative Imaging 9

(a) (b)

Figure 1.8 FDG PET-CT of a 27-year-old female. (a) Transaxial CT of pelvic region and (b) fused PET-CT image of pelvic region
revealing FDG uptake in fluid in the endometrial cavity (arrow) corresponding to menstruation.

(a) (b) (c)

(d) (e) (f)

Figure 1.9 (a) Sagital CT, (b) PET, and (c) fused PET-CT images revealing physiological FDG uptake in the cervical spinal cord (arrows).
(d) Transaxial CT, (e) PET, and (f) fused PET-CT images showing focal FDG uptake at the T11-T12 level in the spinal cord (arrows).
10 Radiology-Nuclear Medicine Diagnostic Imaging: A Correlative Approach

(a) (b)

(c)

Figure 1.10 (a) In a carcinoma larynx patient, the MIP image of FDG PET-CT reveals a hypermetabolic lesion in the neck
corresponding to the site of primary malignancy (black arrow). (b) Fused PET-CT image shows increased FDG uptake in the intercostal
muscles and diaphragmatic crura (white arrows). (c) Transaxial CT of the same region. The augmented FDG uptake in these muscles of
respiration was the result of labored breathing due to narrowing of the airway caused by the laryngeal malignancy.

for CT imaging is in the molar concentration range. Since

use of intravenous contrast is known to be associated with
adverse effects in susceptible population and allergies, cau-
Rotating
X-ray tion needs to be exercised during their use. When diagnos-
tube X ray tic contrast-enhanced CT with intravenous contrast media
beam
is to be performed (after the PET/CT examination), indica-
tions, contraindications, and restrictions have to be
assessed by a qualified physician/radiologist. Medication
that interacts with intravenous contrast (e.g. metformin for
the treatment of diabetes) and relevant medical history,
especially compromised renal function, have to be taken
Stationary into consideration [23].
detector ring

Gastrointestinal Contrast Agent

Figure 1.11 Basic principles of a CT scan.
(i.e. greater signal-to-noise and contrast to noise ratios) and
hence facilitate detection of abnormality. Hence, contrast
imaging agents are often used for better visualization of the
tissue of interest by CT [21, 22].
Today, a wide range of ionic and nonionic contrast agents
is available and effective diagnostic dose of a contrast agent
Depending on the ROI, gastrointestinal luminal contrast
agent may be administered to improve the visualization of
the gastrointestinal tract in CT (unless it is not necessary
for the clinical indication or it is medically contraindi-
cated). This is more commonly done via oral administra-
tion and less commonly by the rectal enema route for
evaluation of colonic pathologies.
It should be noted that the contrast agents alter the atten-
uation caused by tissues and hence result in overestima-
tion of SUV values used in PET quantification (more so
with IV contrast as compared to gastrointestinal) [24].
 Introduction to Correlative Imaging 11

CT Protocols in PET-CT

After the advent of PET-CT in the 1990s, the initial PET-CT

acquisition protocols utilized CT as a fast transmission
source for attenuation correction, with little additional
information for anatomic localization. However, these CT
protocols could not generate diagnostic quality CT images.
These protocols can be largely considered as low-dose CT
scans. The effective dose due to CT procedures in such low-
dose CT scans is typically 3–6 mSv [25].
However, after realizing the logistic advantages of a sin-
gle examination for functional (PET) and morphological
(CT) information, CT is now being utilized as a fast trans-
mission source as well as a state-of-the-art diagnostic tool Figure 1.13 Prototype of a PET-CT scanner available in clinical
to maximize image quality. This protocol involves optimal practice, the GE Discovery IQ Gen2 PET-CT scanner.
acquisition parameters together with oral and intrave-
nous contrast agents. These protocols can be largely con-
sidered as diagnostic CT scans. The effective dose due to space [27]. The PET acquisition typically occurs immedi-
CT procedures in such diagnostic CT scans is typically ately after the CT acquisition to minimize the effects of
11–20 mSv. patient motion.
There are numerous variations in CT protocols and they After reconstruction, the high-resolution anatomical
are discussed in detail in FDG PET-CT guidelines [23, 26]. images (from CT) are overlayed with the functional images
The representative two approaches are shown in (from PET) to provide the precise localization of hyper-
Figure 1.12. metabolic regions. The images consist of PET only, CT
only, and fused PET-CT, which are viewed in the transax-
ial, coronal, and sagittal planes. Additionally, a cine maxi-
Display of Fused PET-CT Images mum intensity projection (MIP) image provides a specific
type of rendering in which the brightest voxel (the voxel
In PET-CT scanners (prototype shown in Figure 1.13), the with maximum FDG uptake) is projected into the 3D
patient lies still on a bed which is then translated through image. This MIP image enables a “gestalt” impression of
fixed mechanically aligned coaxial CT and PET gantries so the study [28]. An example of a typical display is shown in
that the data acquired are precisely co-registered in Figure 1.14.

Protocol1: When CT is used for attenuation correction and localization only (not
intended as a clinically diagnostic CT scan)

CT Low dose PET

topogram CT scan acquisition

Protocol2: When CT is intended to be a diagnostic CT scan

A whole-
body
diagnostic CT
Deep
(with shallow
inspiration
breathing),
thoracic CT,
with 45 seconds
CT with 20 seconds PET
delay after
topogram delay from acquisition
thoracic CT
beginning of
(in
IV contrast
equilibrium
infusion
or venous
phase of
contrast)

Figure 1.12 Schematic representation of representative PET-CT acquisition protocols.

12 Radiology-Nuclear Medicine Diagnostic Imaging: A Correlative Approach

(a) (b) (c) (d)

(e) (f) (g)

(h) (i) (j)

Figure 1.14 Staging FDG PET-CT of a 53-year-old female diagnosed with locally advanced carcinoma of the left breast (blue arrow)
with metastatic lesion in body of D7 vertebra (red arrow). The following components of PET-CT are seen: (a) maximum intensity
projection (MIP) image, (b) trans-axial PET only image, (c) coronal PET only image, (d) sagittal PET only image, (e) trans-axial CT only
image, (f) coronal CT only image, (g) sagittal CT only image, (h) trans-axial PET-CT fusion image, (i) coronal PET-CT fusion image,
(j) sagittal PET-CT fusion image

Artifacts in PET-CT Fusion
Recent PET-CT scanners allow excellent fusion of the PET
and CT images and thus improve lesion localization and
interpretation accuracy. Moreover, the employment of the
CT data for attenuation correction has led to high patient
throughput [29]. Although PET-CT imaging offers many
advantages, this dual-modality imaging also poses some
technical challenges due to a few artifacts. The reader inter-
preting PET-CT scans needs to be aware of these limitations.
The artifacts can be broadly divided into following
categories:
1) Motion artifacts (respiratory or patient related): Although
the CT and PET acquisitions are performed without
changing the patient position, voluntary or involuntary
movements of patient can result in misregistration of
PET and CT images. Most commonly such misregistra-
tion artifacts are observed in lesions of the lungs and
liver. An example is shown in Figure 1.15.
Efforts have been made to minimize such image degra-
dation by the generation of a respiratory motion cor-
rected or four-dimensional PET-CT during which the
PET data are acquired in synchronization with respira-
tory motion [30].
2) Attenuation correction artifacts: The presence of high-
density material in the patient’s body either in the form
of high-density material like bone cement or venous
pooling of intravenous contrast/barium from previous
studies in bowel loops can result in artifactual FDG
uptake due to exaggerated attenuation correction at
these sites. A clinical example is shown in Figure 1.16.
3) Beam hardening artifact: This artifact appears as multiple
linear bands of abnormal attenuation traversing a body
part adjacent to high-attenuation objects, such as metal
prosthesis, dental fillings, chemo ports, and pacemakers.
Patients need to be instructed to remove metallic objects
before scan acquisition and a note should be made of
fixed/in situ metallic prosthesis/implants. An example is
shown Figure 1.17. Some implants/prosthesis can result
 (a) (b) (c)

(d) (e) (f)

Figure 1.15 50-year-old male, known smoker, referred for characterization of a solitary pulmonary nodule in the basal region of the
lower lobe of the right lung. (a) A focus of increased FDG uptake is noted (red arrow), which does not correspond to any morphological
abnormality in fused PET-CT (b) and CT only (c). The acquisitions were repeated with shallow breathing to minimize the lung motion
and the second set of images (d)–(f) reveal focal FDG uptake in a 14 × 14 mm sized nodule in the basal region of the lower lobe of the
right lung (blue arrow), suspicious of neoplastic pathology.

(a) (b)

(c)

(d)

Figure 1.16 MIP image of FDG PET-CT of a 36-year-old female for staging lymphoma. The focal uptake observed in the right axillary
region (black arrows in (a) and (b), and white arrow in (c)) was artifactual due to pooling of intravenous contrast material in the right
subclavian vein. The high density of contrast (red arrow in (d)) resulted in high attenuation correction and resultant artifactual FDG
uptake in the PET image.
14 Radiology-Nuclear Medicine Diagnostic Imaging: A Correlative Approach

in false-positive PET findings due to changes in attenua-
tion correction factors.
A similar artifact can be seen when the PET-CT scan is
acquired with the hands on the sides of the trunk and
hence the easiest way to prevent this artifact is to per-
form the scan with arms up or down, depending on
clinical indication.
4) Truncation artifact: Truncation artifacts in PET-CT are
due to the difference in size of the FOV between the CT
(50 cm) and PET (70 cm) tomographs [31]. These artifacts
are frequently seen in large patients or patients scanned
with arms down, such as in the case of head and neck
malignancy. When a patient extends beyond the CT FOV,
the extended part of the anatomy is truncated and conse-
quently is not represented in the reconstructed CT image.
Truncation also produces streaking artifacts at the edge
of the CT image, resulting in an overestimation of the
attenuation coefficients used to correct the PET data.
This increase in attenuation coefficients creates a rim of
high activity at the truncation edge (see the example in
Figure 1.18), potentially resulting in misinterpretation of
the PET scan [32]. Therefore, in PET-CT imaging, it is

(a) (b)

(c) (d)

Figure 1.17 Beam hardening artifact caused by a metallic implant in the right femur, seen as linear bands of abnormal attenuation
(arrows in (a)–(c)). No artifact is noted in the PET-only image (d).

(a) (b) (c)

Figure 1.18 Truncation artifact in a large patient resulting in the rim of FDG uptake in PET image (a, arrow), loss of information in CT
only image (b), and FDG uptake without morphological data in fused PET-CT (c, arrow).
 Introduction to Correlative Imaging 15

crucial that technologists carefully position the patient at
the center of the FOV and with arms above the head to
reduce truncation artifacts [29].
5) Radiopharmaceutical related: Although relatively rare,
focal FDG uptake (or other PET radiotracer uptake)
without any CT demonstrable lesion needs to be
interpreted with caution, especially in lung paren-
chyma (see the example in Figure 1.19). Such uptake
can be the result of iatrogenic FDG micro-embolus at
the time of injection [33] and when such a finding can
affect management of a patient, a follow-up scan can
be performed to avoid false-positive interpretation. In
the next section, few clinical case examples present
(Figures 1.20–1.22).

(a) (b) (c)

Figure 1.19 Focal FDG uptake seen in the PET image (a, arrow) and fused PET-CT (b) does not correspond to any nodule/lesion in the
corresponding CT trans-axial slice of the right lung (c). Such a pattern can be the result of an iatrogenic micro-embolus of FDG caused
during injection.

(a) (b) (c)

(d) (e)

Figure 1.20 A 28-year-old male recently diagnosed with non-Hodgkin’s lymphoma for staging FDG PET-CT evaluation. The supra-
diaphragmatic and infra-diaphragmatic lymphadenopathy was apparent on CT and was suggestive of stage III NHL. However, the
hypermetabolism in spleen (a and c, arrow) and left iliac bone (e, arrow) could be appreciated in PET and fused PET-CT images and
hence indicated splenic as well as bone marrow involvement, upstaging disease to stage IV. Note that in the CT-only images (b) and
(d) the spleen and left iliac bone appear unremarkable.
16 Radiology-Nuclear Medicine Diagnostic Imaging: A Correlative Approach

FDG PET-CT Clinical Examples PET-CT Tracers Beyond FDG

The following section consists of the pictorial demon-
stration of clinical case examples (Figures 1.20–1.22)
where fusion imaging of FDG PET and CT resulted in
accurate diagnosis of pathology and its extent that would
have been otherwise difficult to reach.
Although 18-F-FDG is the most widely used tracer in
fusion imaging in the form of PET-CT, many other RPs
have made a significant impact in patient management and
have become part of routine patient management. The list
of such RPs is exhaustive and beyond the scope of this
chapter; a few common ones are listed in Table 1.3 [34–38]
with case examples shown in Figures 1.23–1.25.

Table 1.3 PET beyond FDG: the important contemporary tracers and their clinical applications.

PET radiopharmaceutical Mechanism of uptake Clinical use

Gallium-68 and F-18 PSMA Binding to PSMA Prostate carcinoma: biochemical

labeled PSMA targeted ligands
(small-molecule PSMA inhibitors)
Gallium-68 DOTANOC/
DOTATOC/DOTATATE (DOTA-
conjugated peptides)
Fluorine-18 fluoro-dopamine
Fluorine-18 sodium fluoride
Binding with somatostatin receptors
expressed in neuroendocrine tumor cells
Analog of l-DOPA, to trace the
dopaminergic pathway and to evaluate
striatal dopaminergic presynaptic function
18
F is substituted for hydroxyl groups in
hydroxyapatite and covalently bonds to
the surface of new bone
recurrence, staging high-risk cases, and
treatment planning for peptide receptor
radioligand therapy
Neuroendocrine tumor imaging and
treatment planning for peptide receptor
radionuclide therapy
Evaluation of movement disorders
Evaluation of congenital hyperinsulinemia
Diagnosis of skeletal metastases

DOPA, dihydroxyphenylalanine [2-amino-3-(3,4-dihydroxyphenyl) propanoic acid; DOTA, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic

acid; DOTANOC, DOTA-Nal3-octreotide; DOTATOC, DOTA-Tyr3-octreotide; DOTATATE, DOTA-Tyr3-octreotate; FDG, fluorodeoxyglucose;
PET, positron emission tomography; PSMA, prostate specific membrane antigen.

(a) (b)

Pancreatic duct

Common bile duct

Figure 1.21 A 56-year-old male complained of chronic, intermittent abdominal pain and recent onset jaundice, nausea. Ultrasonography
revealed an overdistended gall bladder without any calculus. FDG PET-CT was performed with suspicion of pancreatico-biliary neoplastic
pathology. (a) The contrast-enhanced CT revealed a dilated pancreatic duct and common bile duct, the “double duct sign” (white arrow),
indicating pathology in ampullary region. However, on contrast-enhanced CT alone no obvious morphological lesion could be identified
in the ampullary/duodenal region. However, in the FDG PET images, focal hypermetabolism is seen in the right lumbar region of the
abdomen. When the PET and CT images are fused (b), the hypermetabolism corresponds to the ampullary region of the duodenum (green
arrow) and indicates an ampullary lesion obstructing the pancreatic and common bile ducts. On endoscopy, an ulcerated lesion was found
in the second part of the duodenum, which revealed ampullary carcinoma on histopathology.
 Introduction to Correlative Imaging 17

(a) (b) (c) (d)

(e) (f)

Figure 1.22 Pre- and postchemotherapy FDG PET-CTs of a metastatic carcinoma rectum. The pretherapy PET-CT MIP (a), fused PET-CT
(c), and CT-only (d) images reveal FDG avid hepatic metastasis. Posttreatment images (b), (e), and (f) reveal complete metabolic
response, as seen by resolution of FDG uptake and partial morphological regression, as seen by the reduction in the size of the lesion.

(a) (b) (c)

Figure 1.23 MIP image of 68Ga-PSMA-11 PET-CT for evaluation of biochemical recurrence of prostate carcinoma in a 61-year-old
male. Increased PSMA expression seen in pelvic region (a, black arrow). (b) CT and fused PET-CT reveal increased PSMA expression in
perirectal lymph nodes (white arrows). (d) Scan pattern suggests metastatic lymphadenopathy as a cause of rising PSA levels.

another powerful correlative imaging tool in the future.

SPECT–CT Imaging
Introduction
Among the fusion or correlative imaging modalities,
PET-CT is the often discussed modality, mainly due to its
widespread clinical and research applications, although we
must emphasize the potential and increasing applications
of SPECT–CT, which is often underestimated and may be
Gamma camera (Figure 1.26) has been in use for getting
functional information on the physiological, biochemical,
and metabolic processes in the various organs in the body.
The tracer used in gamma camera imaging is usually spe-
cifically targeted to obtain information from a particular
organ system. Hence, once administered into the patient’s
body, the tracer accumulates in the target organ system.
The more specific the tracer, the more information from
 (a) (b) (c)

(d) (e)

Figure 1.24 MIP image of 68Ga DOTA-Nal3-octreotide PET-CT images of a 51-year-old male patient with clinical suspicion of
neuroendocrine tumor. He complained of recurrent vomiting and abdominal pain, and was found to have substantially elevated serum
chromogranin A levels. (b) Transaxial CT image and (c) fused PET-CT revealed increased somatostatin receptor expression in a small
nodular lesion in the second part of the duodenum (white arrow). (d) Transaxial CT revealed enlarged perilesional lymph node.
(e) Increased somatostatin expression was seen in the enlarged perilesional lymph node (blue arrow). Biopsy of the duodenal lesion
revealed grade 1 neuroendocrine tumor.

(a) (b)

(c) (d)

Figure 1.25 (a) and (b) MIP images of 18F-fluoro-DOPA PET-CT of a 1-month-old baby with recurrent severe hypoglycemia due to
congenital hyperinsulinism. This rare and grave condition is the result of islet cell hyperplasia, which can be either focal or diffuse.
(c) and (d) Transaxial fused PET-CT images reveal diffuse radioactive dopamine uptake was noted in the pancreas, marked with arrows,
suggestive of diffuse islet cell hyperplasia. In the focal type only partial pancreatectomy of the hyperfunctioning focus is performed,
while in the diffuse type a near-total pancreatectomy may be required.

Figure 1.26 Schematic representation of gamma
camera.
the target organ may be collected about a particular patho-
physiological process. However, at the same time, what-
ever little morphological information is obtained by
background tracer activity diminishes significantly. Hence
nuclear medicine techniques often lack anatomical land-
marks. Also, there is definite loss of data in the planar
imaging due to the attenuation of gamma rays coming
from organs deep inside the body.
SPECT entails 3D reconstruction of tracer distribution
within the patient body with the help of data collected by
rotating detectors around the patient body. This helps to
achieve better anatomical information, for example in
the case of bone scan or myocardial perfusion imaging.
CT scanning, on the other hand, is a 3D reconstruction of
X-ray attenuation value maps providing morphological
details like size, shape, and location. Use of contrast
agent in CT primarily provides information about perfu-
sion and the changes in perfusion pattern occurring in
various disease processes. However, CT often does not
provide any information on the functional or metabolic
status of organs in the body. Many disease processes
show pathophysiological changes much before morpho-
logical changes are manifested. Also, in presence of ana-
tomical distortions secondary to various treatments,
anatomical imaging interpretations are difficult and
often uncertain because of changes in symmetry and per-
fusion pattern.
Hence it is of vital importance to understand that
nuclear medicine (SPECT) and anatomical imaging (CT)
are not competitive to each other, but in fact complimen-
tary in nature. The fundamental advantages of this are as
follows:
Introduction to Correlative Imaging 19
Processing
computer
Image on display monitor
Photomultiplier tubes (PMTs)
{Conversion of light to electrical signal}
Detector crystal [Nal(TI)]
{Conversion of gamma rays to light}
Collimator
Source of radioactivity
(Patient)
i) Combined SPECT-CT images have the best of both
worlds. They have all the anatomical information lack-
ing in SPECT images and functional information lack-
ing in CT images. CT also helps in proper localization
of tracer uptake to ultimately help in correct diagnosis
and treatment.
ii) Not only this, CT attenuation maps are used for
attenuation correction and this improves the quality
of SPECT images. There are many applications of
SPECT-CT that are well established clinically. As
new advanced systems are becoming widely available,
further improving the accuracy of image fusion and
shortening acquisition times, the newer applications
are becoming more evident. Apart from applications
in oncology, interesting uses of SPECT-CT are seen
in the areas of minimally invasive surgery and cardi-
ology. We shall start our treatise with some technical
information about these systems before going into
the clinical applications.
SPECT–CT System Information
Combining SPECT and CT images acquired from differ-
ent standalone machines has often been challenging. This
is because usually the studies are acquired on different
dates, on different machines by different operators using
different protocols. This creates differences in the posi-
tion of the patient body, extremities as well as spinal cur-
vatures, as table positions may differ with different
systems. Furthermore, it is not possible to match respira-
tory, cardiac motion, and position of stomach, intestines,
20 Radiology-Nuclear Medicine Diagnostic Imaging: A Correlative Approach
and urinary system at different time frames. Software
fusion techniques have been developed which can regis-
ter and fuse images from multiple sources [39, 40], but
they are best suited for correlating images from rigid struc-
tures such as the brain [41] and skeleton [42, 43]. However,
for thorax and abdomen, due to inherent movement of
internal organs, software fusion has remained challeng-
ing. Data sets from two fundamentally different imaging
modalities with different spatial resolution and with few
common landmarks make it further complicated. A sys-
tem offering same geometry for acquisition of SPECT and
CT images almost simultaneously, such as SPECT-CT
scanning, offers much better data sets for fusion. Here the
patient remains on the same table and in the same posi-
tion while undergoing SPECT and CT acquisitions sepa-
rated by a few minutes.
The practical advantages of SPECT-CT fusion imaging
are multifold:
i) These systems are able to superimpose functional
information from nuclear medicine data sets onto ana-
tomical information from CT scans, greatly improving
the confidence of the reporting diagnostician.
ii) These systems are able to facilitate attenuation correc-
tion of SPECT data with patient-specific attenuation
maps acquired from CT [44, 45]. Because of this, there
is improvement in the spatial resolution, contrast, and
signal-to-noise ratio of the image.
iii) There is improvement in the functional data quality
aided by CT, which shows great promise in quantifica-
tion of RP uptake [46, 47]. This is very useful for (i)
better radiation dosimetry [48, 49] and (ii) monitoring
response to therapy.
The concept of combining structural and functional
information was conceived and implemented in prototype
SPECT-CT gantry
Patient table SPECT detectors
Figure 1.27 Schematic diagram of the modern SPECT-CT system.
form at the very beginning of emission and transmission
CT, most notably the work by Kuhl, Hale, and Eaton, who
obtained the first trans-axial transmission CT scan of a
patient’s thorax using their Mark II brain SPECT scanner
in the mid-1960s [50]. However, use of transmission imag-
ing with an external radionuclide transmission source was
introduced for attenuation correction in SPECT [51, 52]
and PET [53, 54] only in the 1980s. In this system, external
transmission scanning was used with SPECT to perform
both attenuation correction and anatomical localization.
However, a transmission scan provides poor quality
anatomical details and contrast resolution, hence these
systems never grew into routine applications. Over the last
decade or so, combined SPECT-CT scanners have become
commercially available which acquire data from SPECT
and CT on the same gantry. The patient remains in same
position and on the same table, which is then sequentially
moved from one modality to another. The final data
acquired is then transferred to a single computer which
does data correction, image reconstruction, integration,
and display and allows analysis for better diagnosis.
The early SPECT-CT systems tried simultaneous acqui-
sition of SPECT and CT data [55, 56], but the problem
with a simultaneous SPECT-CT acquisition system was in
designing a common detector with sufficient temporal
and energy resolution to discriminate the primary radio-
nuclide photons from both the X-ray signal and the scat-
ter of the radionuclide photons. This problem remains
unsolved. The “modern” SPECT-CT system was originally
developed by Hasegawa et al. at the University of
California, San Francisco in the mid-1990s [45]. These
systems have SPECT and CT gantries in tandem (in-line)
which can acquire patient data sequentially and send it to
the same computer for further fusion and processing
(Figure 1.27).
CT

General SPECT–CT Protocols
The first commercial SPECT-CT combination that was
designed as a single unit was the GE Millenium™ hybrid
SPECT/PET/CT camera equipped with a HawkEye™
single-slice CT (GE Healthcare, Haifa, Israel). The CT
produced images with a slice thickness of 1 cm and a
256 × 256 matrix size with a spatial resolution of about
3.5 mm. Because of its coarse resolution, the CT was not
regarded as a diagnostic CT. Reconstruction was per-
formed using filtered back projection. The system was
also offered with a 1-in. crystal and a coincidence unit for
PET imaging. This system was the commercial implemen-
tation of the very successful research by the late Hasegawa
et al. [57].
Almost all current SPECT-CT systems offer high-
resolution diagnostic CT units as part of their SPECT-CT
systems. One of the manufacturers (Mediso) even offers a
complete SPECT/CT/PET with high-resolution lute-
tium-yttrium oxyorthosilicate (LYSO) detector technology
as part of their AnyScan family of systems. The CT scan in
these devices is a diagnostic CT scan which is used for
attenuation correction based on individual patient-based
tissue density data. The SPECT-CT workstations allow
image reconstruction, and three-plane (transaxial, coronal,
sagittal) and 3D display, including MIP and surface volume
rendering. SPECT, CT, and fused images are shown on the
same screen, and an interconnected pointer is available to
exactly colocalize the morphological and functional areas
of interest identified in either one of the two study
components.
The cost of SPECT-CT systems is considerably higher
than that of a conventional gamma camera, especially for
devices including a full diagnostic capability CT. Higher
cost has constrained the availability of this technology to
places with limited financial resources. New SPECT
devices have recently been developed using CdTe/CdZnTe
semiconductors instead of the classic NaI (Tl) scintillation
crystals. Such newer systems are smaller, and have higher
sensitivity and intrinsic resolution than conventional
cameras.
SPECT–CT Acquisition
Most clinical SPECT systems still rely on the Anger camera
principle discussed earlier, where the location of a photon
interaction (i.e. scintillation) site in the body is calculated as
the center of gravity of the position-dependent energy sig-
nals from a two-dimensional (2D) array of photomultiplier
tubes (PMTs) attached to the back of the scintillation crys-
tal [58]. The available NaI (Tl) crystal thicknesses vary
Introduction to Correlative Imaging 21
between 3/8 and 3/4 in. (9.5 and 19 mm) depending on the
intended usage for radionuclides emitting lower energy pho-
tons (e.g. 99mTc) and/or higher energy photons (e.g. 131I).
Thicker crystals improve the photo-peak efficiency but
degrade the intrinsic spatial resolution.
Acquisition on SPECT-CT systems is performed in a
sequential mode. The SPECT-CT systems using a diagnostic
CT component have higher spatial resolution and faster
scanning time. However, diagnostic CT delivers higher
radiation doses. The SPECT component is acquired by a
rotating, dual-head, variable angle sodium-iodide scintilla-
tion camera. SPECT acquisition currently requires a routine
scanning time of approximately 20–30 minutes, depending
on the radiotracer and the axial length of the body area
scanned. CT is usually acquired in matrices of 512 × 512 with
the newest CT scanners or 256 × 256 in older scanners, and
has to be resized into slices with the same pixel format and
slice width as SPECT. SPECT is reconstructed using itera-
tive methods incorporating photon attenuation correction
based on the X-ray transmission map and scatter correction.
Since X-ray and radionuclide data are not acquired simulta-
neously, the SPECT images are not contaminated by scatter
radiation generated during the X-ray image acquisition.
Also, since the patient is not removed from the table, both
imaging components are acquired with a consistent and
identical patient position, allowing accurate image registra-
tion if we assume that the patient has not moved during the
entire duration of the SPECT-CT study.
The current SPECT systems are equipped with detection
devices or sensors to automatically calculate noncircular
orbits: the detection methods can be based on optical detec-
tion using light-emitting diodes. Aside from the safety
aspect, noncircular orbits ensure closer distances to the
patient for each of the SPECT projections as well as easy
setup procedures, which together reduce the overall time
that the patient spends on the imaging table. Companies
now offer advanced and integrated diagnostic SPECT-CT
solutions with 2-, 6-, or 16-slice diagnostic CTs. Basically,
the SPECT-CT is a hybrid or a combination of each of the
two systems that have the same characteristics as the
respective standalone devices.
Image Reconstruction
Most of the newer SPECT systems use statistical iterative
reconstruction for creating images [59, 60]. An iterative
procedure includes some kind of model of how the images
are formed by the acquisition system. For a SPECT system,
an image is formed by the collimation of emitted photons
such that only those photons parallel to the collimator hole
will interact with the crystal and produce scintillation
22 Radiology-Nuclear Medicine Diagnostic Imaging: A Correlative Approach
events. Hence, these so-called projections are created as 2D
representations of all photons detected along the projec-
tion lines and this gives rise to a distance-dependent reso-
lution. The greater the distance of the camera head from
the radioactive source, the poorer the resolution. There is
no information about source depth in the 2D projections.
The purpose of the reconstruction algorithm is therefore to
create an estimate of the source distribution in 3D. From
the CT in SPECT-CT systems, attenuation maps are gener-
ated and incorporated in the image formation model.
In an iterative reconstruction algorithm, one starts with
an initial estimate of the internal and unknown radionu-
clide distribution. This estimate is usually an image set
with equal and constant voxel values. SPECT projections
are then calculated from the initial estimate using a com-
puter model of the imaging system. The underlying
assumption is that if the calculated projections match the
measured projections, then the internal unknown activity
distribution in the patient matches the estimate. Initially,
these are most likely nonagreeing, so the initial estimate
needs to be modified. Therefore, updates are made in the
estimate based on a comparison between calculated projec-
tions of the estimate using the physics of the imaging pro-
cess and the measured projections. By back projection, the
deviations between these two projection sets finally form
an error image of weighting factors that is used to update
the initial image estimate. This procedure is placed in an
iterative loop in which the calculated and measured projec-
tions are compared until the deviation is smaller than a
selected criterion (convergence has been reached). Hence,
when this happens, the reconstruction loop is stopped.
However, in actual practice, as projection data is noisy, the
iterative reconstruction procedures are stopped after only a
small number of iterations because the noise in the final
image goes on increasing for a large number of iterations.
The most popular iterative reconstruction algorithm imple-
mented is ordered subset expectation maximization (OS-
EM) [61] due to the speed with which it reaches a good
estimate of the activity distribution.
However, there are many other factors, such as nonho-
mogeneous photon attenuation, contribution from scat-
tered photons, and blurring due to the collimator response,
which need to be accounted for during reconstruction of
the image. The compensation for these factors is relatively
easy in iterative reconstruction, but there are still some
issues when combining these two systems. It should be
remembered that a SPECT acquisition is averaged over
many respiratory cycles, which blurs the image, while rap-
idly acquired CT images are instantaneous images and may
not match with the averaged SPECT image. The spatial
resolution of the SPECT system is also far lower than that
of CT. Hence, if high-resolution CT images are used for
attenuation correction, there is a possibility that artifacts
may appear at boundaries between different attenuating
tissues because of the spill-out of events. Often this effect is
reduced by smoothing the CT images with a Gaussian ker-
nel that results in a spatial resolution of the CT images
comparable with the spatial resolution of the SPECT
images. Also, depending on the acquisition parameters
(voltage and mAs), the CT image may not be optimal for
attenuation correction and the scaling from the X-ray
bremsstrahlung spectra to the specific photon energy used
in SPECT may not be optimal. Hence, when using CT only
for attenuation correction, so-called low-dose protocols
can be used which are optimized, such as a longer scan-
ning time to average the respiratory movements and
matched spatial resolutions [62].
The problem of scatter correction has been taken care of
by various methods. Siemens and GE have implemented
some form of the dual-energy window method based on the
estimation of scatter from additional energy windows for
subtraction from projection data or used within iterative
reconstruction methods as an additive term [63]. However,
it is generally known that the distribution of scatter in addi-
tional lower scatter windows does not reproduce the scatter
distribution in the main photo-peak energy window.
Alternatively, model-based scatter compensation has been
used that does not rely on additional energy window data
collection. Instead, it models the scatter in the main photo-
peak energy window by using pre-calculated scatter kernels
or in real-time calculates the scatter based on theoretical
cross-sections of first-order scattering. Philips has imple-
mented a version of the effective scatter source estimator
method, originally developed by Frey and Tsui [64].
There is also a need for some compensation for the lim-
ited spatial resolution due to the collimator design. This is
generally implemented in the iterative reconstruction algo-
rithm, modeling the depth-dependent blurring caused by
photons that reach the detectors. The effect of partial vol-
ume is an apparent reduction of the radioactive count
density/X-ray density that occurs when an organ/tumor/
defect only partially resides within the “sensitive volume of
the imaging instrument (in space or time)” [65–68]. From
the review of Erlandsson et al. [68] it is clear that an exten-
sive body of work exists in an effort to minimize the partial
volume effect. The main aim of partial volume correction
(as well as resolution correction) is to improve the quanti-
tative accuracy of the structure under investigation. CT can
be used for correction of partial volume in SPECT images
owing to its high sampling frequency.
Patient body movement can occur during both the SPECT
and CT portions of the study. The acquisition times for con-
ventional SPECT–CT systems can vary from 10 minutes to
more than 30 minutes depending on area scanned and
 Introduction to Correlative Imaging 23

count rate. During acquisition, SPECT typically takes much Table 1.4 The major contrasting points between conventional
more time than CT. All manufacturers offer registration (NaI-based) gamma cameras and a cadmium–zinc–telluride
(CZT)-based SPECT-CT system.
tools to manually or automatically register SPECT and CT
in case movement occurs between those two scans. The
Conventional gamma CZT-based
motion during the CT portion of the acquisition is usually Attributes camera (NaI) gamma camera
minimized owing to short scan times as well as breadth-
holding by the patient for diagnostic CT scan. All manufac- Type of crystal Scintillation Semiconductor
turers have some form of motion correction for SPECT itself Interaction of Produces light Produces
using the consistency of the projections. These algorithms gamma rays electron–hole
usually work best for small and simple motions. However, pair
for excessive and complex motions, the SPECT-CT acquisi- Photomultiplier Necessary to convert Not required
tion needs to be repeated. tube light signal to electrical
signal and amplify it
Detector Bulky Sleek
assembly
New SPECT–CT Scanners with Solid-state
Sensitivity + +++
Detectors
Spatial + +++
resolution
The most common scintillation material used in gamma
camera is NaI(Tl). It is readily available and cost-effective. Energy + +++
resolution
If we review the principal characteristic of gamma cam-
Image contrast + +++
eras, then the absorbed photon energy is converted to visi-
ble light in proportion to the deposited energy and this Image quality + +++
light is then detected by PMTs. PMTs convert this light to Acquisition +++ +
time
electrons at the cathode surface of the PMTs and the signal
is amplified using a sequence of dynodes to create an elec- Radiation +++ +
exposure
trical signal. This signal is then processed to get informa-
tion about the energy and position of the original gamma Available field ++ +++
of view
rays. Because there are many steps involved, the uncer-
Cost + +++
tainty in the measured energy signal is quite large, result-
ing in an energy resolution in the order of 10% full width at
half maximum at 140 keV. Furthermore, a large number of
CZT based SPECT–CT system (Discovery NM/CT 870
PMTs are required to determine the location of the interac-
CZT) provides up to 75% reduction in injected dose or scan
tion. That is why the size of the scintillation camera head is
time, improved system spatial resolution, from 4.3 to
quite large and requires sophisticated tuning methods so
2.8 mm, and exceptional energy resolution, 6.3% compared
that all PMTs provide similar amplitude signals for the
to 9.5%, according to data provided by them. They also
same imparted energy.
claim greater than 40% improvement in SPECT contrast-to-
Recently, commercial SPECT systems based on cad-
noise ratio, 67% reduction in detector frame size, from 7.5
mium–zinc–telluride (CdZnTe or simply CZT) have been
to 2.5 cm, and 25% greater optimal FOV than Nal [69].
introduced. CZT is a solid-state detector material that gen-
There are newer CZT systems, such as the VERITON CZT
erates signals from the collection of induced charge created
camera (Spectrum Dynamics, Caesarea, Israel), which are
by the ionizations from photoelectric interactions or
similar to PET-CT cameras in architecture with detectors
Compton scattering. Here each photon is directly con-
arranged in a ring configuration around the patient [70].
verted into an electrical signal. The major advantages of
these new CZT modules are their small size and the
absence of PMTs, which allows for a compact camera. It Clinical Examples of SPECT–CT
also increases the overall system sensitivity significantly.
The improvement in sensitivity can either be used to As there are chapters dedicated to the clinical applications
reduce the acquisition time of a given administered activity of SPECT-CT system later in the book, we restrict ourselves
or reduce the radioactivity administered for the same to a few clinical examples. The selected clinical examples
acquisition time. The major contrasting points between a of SPECT-CT acquisitions shown in Figures 1.28–1.32 are
conventional gamma camera and the CZT-based SPECT-CT such that, if not for combined imaging, the diagnosis might
system are given in Table 1.4. The GE Healthcare full-size have been missed or delayed.
 (a) (b)

(c)

ANTERIOR POSTERIOR

Figure 1.28 A 51-year-old female with a presenting complaint of left hip joint pain. (a) The bone scan showed increased tracer
uptake in the upper part of the left hip joint. (b) and (c) The SPECT-CT scan of the pelvis showed subchondral cysts in the head of the
left femur, suggestive of osteoarthritis. In this case the bone scan helped to find the active osteoblastic reaction in the left hip joint
region as cause of pain and the CT component helped to localize abnormal tracer uptake. The morphological findings of osteoarthritis
on CT added specificity to bone SPECT findings.

(a) (b)

SPECT

CT

SPECT-CT
fused
image

ANTERIOR POSTERIOR

Figure 1.29 A 70-year-old male with diagnosed carcinoma of prostate. His serum PSA level was 34 ng/ml. (a) The whole-body bone
scan shows focal increased tracer uptake in the upper dorsal vertebra. (b) The SPECT-CT scan of the thorax shows increased tracer
uptake corresponding to sclerotic lesion involving the D2 vertebral body consistent with solitary skeletal metastasis. In this case, the
bone scan detected a solitary osteoblastic lesion in the upper dorsal vertebra and CT localized it to the D2 vertebra showing sclerosis,
hence confirming metastatic disease.
 (a)

Early 20 min image Delayed 2 hours image

(b)

Figure 1.30 A 35-year-old male with recurrent pancreatitis. He was found to have elevated serum parathyroid hormone levels during
evaluation and was referred for a 99mTc-MIBI parathyroid scan. (a) Dual phase parathyroid scintigraphy in anterior static images
showing focal abnormal tracer uptake near the lower pole of the left lobe of the thyroid gland (blue arrow) with focal tracer retention
seen in the delayed image. (b) SPECT-CT of the neck showing abnormal tracer uptake corresponding to a 14 × 14 mm nodule in the left
upper paratracheal region inferior to the lower pole of the left lobe of the thyroid gland suggestive of parathyroid adenoma.
The SPECT-CT scan helped in the exact localization of the parathyroid lesion and aided with better surgical planning.

(a) (c) (e)

(d) (f)
(b)

Figure 1.31 A 70-year-old male with chronic kidney disease and suspected pulmonary thromboembolism. The 99mTc-
macroaggregated albumin lung perfusion scan (a, b) showed a perfusion defect in the right middle lobe. The SPECT-CT scan (e, f)
showed a large perfusion defect in the middle lobe of the right lung with no morphological abnormality, such as a space-occupying
lesion, consolidation or fluid accumulation on the CT scan. The CT scan (c, d) showed well-aerated lung parenchyma in the region of
the perfusion defect, potentially eliminating the need for a ventilation scan to diagnose pulmonary thromboembolism.
Another random document with
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 CHAPTER XIII
HOME

It was necessary to stay in Montgomery over night in order to make

railroad connections; so Hazel was able to visit Mr. and Mrs. Jenks
again, while Miss Davis went to a hotel. Mrs. Jenks and her husband
were delighted at the change in Hazel’s appearance. The thin, shy
child had grown almost plump and was full of spirits. She talked gaily
at dinner, she romped with the children, and she gave her host such
a generous good-night hug that he was breathless and disheveled
when it was over.
“Excuse me,” Hazel called as she ran upstairs, “but that is the way
Mr. Perkins likes me to say good-night to him. And, oh,” ecstatically,
“I shall see him next Sunday!”
The following morning Mrs. Jenks put up an enormous box of
luncheons and breakfasts and suppers for Hazel. Such a quantity of
bread and butter sandwiches, such a lot of sliced chicken and hard-
boiled eggs, and a jar of guava jelly with a spoon that didn’t have to
be returned.
“It will be less expensive for you than to get your meals on the train,”
Mrs. Jenks began hesitatingly.
Hazel broke in impetuously, “I know all about it, Mrs. Jenks. I’m not
wanted in the dining car because I’m colored. I’m traveling North as
Miss Davis’s maid, and I’m to do little things for her and to play I
really am a maid. She says her traveling dress hooks up the back
and around the side with about a hundred hooks, and that she could
never wear it except for me. And I must keep her hair smooth for her
because her mother says it is always untidy—it isn’t, it’s beautiful.
And I’m to fan the flies away from her when she takes a nap. As if I
thought flies were on trains! But we are going to play that I am her
maid, to make a game of it, because it is better to do that than to
keep feeling angry. How many meals do I eat? One, two, three, four,
five? This is plenty, for I can get milk and cocoa. I’m going to sleep in
an upper berth, think, and climb up on a ladder! It will be great fun.”
Mrs. Jenks smiled and sighed and put some cakes in the box.
Miss Davis called for Hazel in a carriage, and the little girl felt very
proud as she drove away with her new friend. The station was an
exciting place. Hazel saw a check marked “Boston” put on her trunk
and knew that home was near. She entered the Pullman car with
Miss Davis and held her hand tightly as the porter showed them their
seats. All her safety from insult, she knew, lay in the presence of her
white companion. They sat down together and at length the train
drew out of the station, headed for the North and home.
The little girl looked up at her friend. “I’m trying to think all the time of
Mother,” she said, “but I can’t forget Granny and Scip.”
“You’ll visit them again,” Miss Davis said consolingly. “When people
once begin to travel they never stop.”
The journey was full of interest to Hazel, and not an unkind word was
said to her during the trip. Indeed, an old lady in the seat across the
aisle took a fancy to her, and sent her a big plate of ice-cream from
the dining car. “Two portions, I’m sure,” Miss Davis said when she
heard about it. New York was reached, a din of trolleys and
elevateds and a big, beautiful station with a restaurant where
everyone could sit and eat, and then Boston and home.
It was night when they got off the train at the South Station, and
Hazel trembled as she walked by Miss Davis’s side. If Mother should
miss her! Then she saw a big black man and she rushed toward and
past him and into her mother’s arms.
“I waited a long time for my greeting,” said Mr. Perkins, smoothing
his coat collar, “but it was satisfactory when I got it.”
“Where is Miss Davis?” asked Hazel when she could look about her
again.
“She left her good-bye,” said Mr. Perkins; “she was hurrying to meet
someone, too; perhaps it was her brother, and perhaps it wasn’t.
Come, Little Frog, give me your check. I’ll look after your trunk when
I’ve put you and your mother on the car. You’re coming to dine with
us Sunday.”
How beautiful home looked with its three dear little rooms! The table
was set for supper. There was a big dish of strawberries, white bread
and butter, and a spider on the fire with a lamb chop in it ready to
cook! In a moment Charity came in.
The two little girls flew into one another’s arms.
“My, ain’t you fat, Hazel!” said Charity.
Hazel laughed delightedly. “I like to be fat,” she said.
“I am going to cook your chop,” said Charity, and Mrs. Tyler let her.
“Mother,” said Hazel as she ate her supper, “you don’t know, for you
haven’t been South, how good this chop tastes. There are two things
I don’t want to see again for a long time; one is bacon and the other
is corn bread.” Then, feeling that this might seem ungrateful to
Granny, “they are both good, but I’ve had enough of them.”
“There’s a moving-picture show around the corner,” said Charity,
when Hazel had finished her supper, “want to go? I’ve got two
dimes.”
“Oh, not to-night, Charity.”
“Well, whenever you want, the price is on me.”
Hazel was not allowed to help with the dishes, for she was a visitor
this evening. To-morrow she would slip back into the routine of
home. She and her mother talked and talked far into the night, there
was so much to tell about, and both were so happy. At length Hazel
dropped off to sleep, but her mother lay awake until the dawn
showed her her child’s face again. “How well she looks,” Mrs. Tyler
said again and again to herself. “I did right to send her away.”
“Here is a wash-cloth that I spun and wove for you, Charity,” Hazel
said the next morning and handed it triumphantly to her friend.
Charity looked it over carefully. “I can buy ’em like that for five cents
at Jordan, Marsh’s.”
“Can you?” answered Hazel, trying not to be hurt. “And it took me
days and days to make it.”
“Sure,” said Charity loftily, “didn’t I tell you it was slow down South?”
When Hazel took the same gift to her school-teacher, however, she
heard a very different comment.
“You’ve done a wonderful thing, Hazel,” Miss Grey said. “You’ve
followed an industry from its beginning to the finished product. Next
year, if it is possible, we will get a spinning-wheel and loom and you
can demonstrate the spinning and weaving to the school.”
Hazel repeated this to Charity.
“Bet you’d break your thread,” Charity declared, “when you had to
spin before all the boys and girls.”
The homecoming was very exciting. There was the first Sunday at
church, and the Sunday school service, when they wanted to hear
about their song-books down in Alabama, and the good time at the
Perkins’s and the trolley rides with Charity. Mr. Perkins gave Hazel a
dollar for trolley rides, telling her that she must not forget the city and
its delights.
June came, and one late afternoon Mrs. Tyler returned from her work
looking so happy that Hazel accused her of having a secret.
Mrs. Tyler nodded assent. “You shall hear it after supper,” she said.
So when the dishes were washed they sat down together, and Hazel
heard the secret.
“We are going away for the summer,” said her mother. “I find I can
make more money at my shampooing in the country than here.
Some of my customers go to a beautiful place by the sea and they
promise me plenty of business there.”
“Is it at Revere Beach?” asked Hazel.
“No indeed, goosey, much further than that, ’way down in Maine.”
“More traveling?”
“Yes, more traveling, but not so far as Alabama.”
“I shall miss Charity,” mused Hazel, “but I believe wherever you go
you have to miss somebody. Are there pines in Maine?”
“Pines?”
“Yes, pine trees. Do they grow there?”
“I think so, dear.”
“Then, if there are pine trees, I shall like it very much!”
Just before they left town letters came from Granny and Scip.
“Mother,” said Hazel after reading them, “my heart is content. Scipio
is living with Granny; at least, he is staying there at night. She never
did like living alone, the least bit, and so she got Scip’s father to let
the boy stay with her. She gives him supper and breakfast and
Granny says he was half starved before, and at night they both read
out of the books I left. Granny says they think of me.”
Scipio’s letter was plainly printed and showed constant consultation
with the dictionary.
Dear Sister:
Aunt Ellen has took me in.
I am going to help her pick cotton when it ripes.
The cat is playing by the fire.
Scipio Lee.
“I’m so glad you trimmed my summer hat with the feathers Scip gave
me, Mother,” Hazel said, “I shall tell him about it the next time I
write.”
THE END.
 TRANSCRIBER’S NOTES:
Obvious typographical errors have been corrected.
Inconsistencies in hyphenation have been
standardized.
Archaic or variant spelling has been retained from the
original.
*** END OF THE PROJECT GUTENBERG EBOOK HAZEL ***

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