Full download test bank at ebook ebookmass.

com

Radiology-Nuclear Medicine
Diagnostic Imaging Ali
Gholamrezanezhad

CLICK LINK TO DOWLOAD

https://ebookmass.com/product/radiology-
nuclear-medicine-diagnostic-imaging-ali-
gholamrezanezhad/

ebookmass.com
More products digital (pdf, epub, mobi) instant
download maybe you interests ...

Core Radiology: A Visual Approach to Diagnostic Imaging

https://ebookmass.com/product/core-radiology-a-visual-approach-
to-diagnostic-imaging/

Diagnostic Imaging: Interventional Radiology 3rd

Edition Brandt C. Wible

https://ebookmass.com/product/diagnostic-imaging-interventional-
radiology-3rd-edition-brandt-c-wible/

Essentials of Nuclear Medicine and Molecular Imaging

7th Edition

https://ebookmass.com/product/essentials-of-nuclear-medicine-and-
molecular-imaging-7th-edition/

Grainger & Allison’s Diagnostic Radiology. A Textbook

of Medical Imaging 7th Edition Andreas Adam

https://ebookmass.com/product/grainger-allisons-diagnostic-
radiology-a-textbook-of-medical-imaging-7th-edition-andreas-adam/
Nuclear Medicine and Molecular Imaging: the Requisites
5th Edition Janis P. O'Malley

https://ebookmass.com/product/nuclear-medicine-and-molecular-
imaging-the-requisites-5th-edition-janis-p-omalley/

Coronavirus Disease 2019 (Covid-19): A Clinical Guide

1st Edition Ali Gholamrezanezhad

https://ebookmass.com/product/coronavirus-
disease-2019-covid-19-a-clinical-guide-1st-edition-ali-
gholamrezanezhad/

Grainger & Allison’s Diagnostic Radiology. Essentials

Lee Alexander Grant

https://ebookmass.com/product/grainger-allisons-diagnostic-
radiology-essentials-lee-alexander-grant/

Textbook of Radiology And Imaging, Vol 2 Bharat

Aggarwal

https://ebookmass.com/product/textbook-of-radiology-and-imaging-
vol-2-bharat-aggarwal/

Diagnostic Imaging Genitourinary 4th Edition Ganeh

Fananapazir

https://ebookmass.com/product/diagnostic-imaging-
genitourinary-4th-edition-ganeh-fananapazir/
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
© 2023 John Wiley & Sons Ltd

All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means,
electronic, mechanical, photocopying, recording or otherwise, except as permitted by law. Advice on how to obtain permission to reuse material
from this title is available at http://www.wiley.com/go/permissions.

The right of Ali Gholamrezanezhad, Majid Assadi, and Hossein Jadvar to be identified as the authors of the editorial material in this work has
been asserted in accordance with law.

Registered Offices
John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, USA
John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK

For details of our global editorial offices, customer services, and more information about Wiley products visit us at www.wiley.com.

Wiley also publishes its books in a variety of electronic formats and by print-on-demand. Some content that appears in standard print versions
of this book may not be available in other formats.

Trademarks: Wiley and the Wiley logo are trademarks or registered trademarks of John Wiley & Sons, Inc. and/or its affiliates in the United
States and other countries and may not be used without written permission. All other trademarks are the property of their respective owners.
John Wiley & Sons, Inc. is not associated with any product or vendor mentioned in this book.

Limit of Liability/Disclaimer of Warranty

The contents of this work are intended to further general scientific research, understanding, and discussion only and are not intended and
should not be relied upon as recommending or promoting scientific method, diagnosis, or treatment by physicians for any particular patient.
In view of ongoing research, equipment modifications, changes in governmental regulations, and the constant flow of information relating
to the use of medicines, equipment, and devices, the reader is urged to review and evaluate the information provided in the package insert
or instructions for each medicine, equipment, or device for, among other things, any changes in the instructions or indication of usage and
for added warnings and precautions. While the publisher and authors have used their best efforts in preparing this work, they make no
representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties,
including without limitation any implied warranties of merchantability or fitness for a particular purpose. No warranty may be created or
extended by sales representatives, written sales materials or promotional statements for this work. The fact that an organization, website, or
product is referred to in this work as a citation and/or potential source of further information does not mean that the publisher and authors
endorse the information or services the organization, website, or product may provide or recommendations it may make. This work is sold with
the understanding that the publisher is not engaged in rendering professional services. The advice and strategies contained herein may not be
suitable for your situation. You should consult with a specialist where appropriate. Further, readers should be aware that websites listed in this
work may have changed or disappeared between when this work was written and when it is read. Neither the publisher nor authors shall be
liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages.

Library of Congress Cataloging-in-Publication Data applied for

ISBN: 9781119603610 (hardback)

Cover Design: Wiley

Cover Images: © semakokal/iStock/Getty Images, wenht/iStock/Getty Images

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 Unit of Nuclear Medicine, Fondazione Istituto G. Giglio,
Department of Nuclear Medicine, Namazi Hospital, Cefalù, Italy
Shiraz, Iran
Nolan Altman
Ahmad Abdlkadir Nicklaus Children’s Hospital, Miami, FL, USA
Department of Nuclear Medicine, King Hussein Cancer
Center, Amman, Jordan
HamidReza Amini
Khatam PET-CT Center, Khatam Hospital, Tehran, Iran
Fawzi Abuhijla
Department of Radiation Oncology, King Hussein Cancer
Center, Amman, Jordan Paolo Artoli
Nuclear Medicine Unit, Department of Medicine,
Jay Acharya University of Padua, Padua, Italy
Radiology, Keck School of Medicine of USC, HCCII Lower
Level Radiology, Los Angeles, CA, USA Majid Assadi
Department of Radiology, School of Medicine, Nuclear
Kanhaiyalal Agrawal Medicine and Molecular Imaging Research Center
Department of Nuclear Medicine, All India Institute of Bushehr University of Medical Sciences
Medical Sciences, Bhubaneswar, India 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, Diagnostic and Interventional Radiology, Department of
IA, USA Translational Research and Advanced Technologies in
Medicine and Surgery, University of Pisa, Pisa, Italy
Liesl Eibschutz
Department of Radiology, Keck School of Medicine, M. Gaeta
University of Southern California, Los Angeles, CA, USA Section of Radiological Sciences, Department of
Biomedical Sciences and Morphological and Functional
Caldon J. Esdaille Imaging, University of Messina, Messina, Italy
Howard University College of Medicine,
Washington, DC, USA Daniela Garcia
Department of Radiology, Mercy Catholic Medical Center,
Azadeh Eslambolchi Darby, PA, USA
Pediatric Radiology Section, Mallinckrodt Institute of
Radiology, Washington University in St Louis, School of Pavel Gelezhe
Medicine, St. Louis, MO, USA Research and Practical Clinical Center for Diagnostics and
Telemedicine Technologies of the Moscow Health Care
Laura Evangelista Department, Moscow, Russia
Nuclear Medicine Unit, Department of Medicine, European Medical Center, Radiology Department,
University of Padua, Padua, Italy Moscow, Russia

Saum Ghodoussipour
Murat Fani Bozkurt
Rutgers Robert Wood Johnson Medical School, New
Department of Nuclear Medicine, Hacettepe University
Brunswick, NJ, USA
Faculty of Medicine, Ankara, Turkey
Section of Urologic Oncology, Rutgers Cancer Institute of
New Jersey, New Brunswick, NJ, USA
P. Ferrari
Department of Medical Physics, Central Hospital of
Ali Gholamrezanezhad
Bolzano, Bolzano, Italy
Department of Radiology, Keck School of Medicine,
University of Southern California, Los Angeles, CA, USA
Brandon K. K. Fields
Keck School of Medicine, University of Southern
Edoardo Giacomello
California, Los Angeles, CA, USA
Dipartimento di Elettronica, Informazione e
Bioingegneria, Politecnico di Milano, Milano, Italy
Russell Flato
Department of Radiology, Keck School of Medicine, Jordan S. Gross
University of Southern California, Los Angeles, CA, USA Department of Radiology, University of California, Los
Angeles, Los Angeles, CA, USA
A. Fracchetti
Department of Medical Physics, Central Hospital of Mariano Grosso
Bolzano, Bolzano, Italy Regional Center of Nuclear Medicine, Department of
Translational Research and Advanced Technologies in
Marco Frigo Medicine and Surgery, University of Pisa, Pisa, Italy
Nuclear Medicine Unit, Department of Medicine,
University of Padua, Padua, Italy Amit Gupta
Radiology, Medicine and Biomedical Engineering,
Jerry W. Froelich Case Western Reserve University School of Medicine,
Radiology, University of Minnesota, Minneapolis, MN, USA Cleveland, OH, USA
Cancer Imaging Program, Case Comprehensive Cancer
Hiroyuki Fujii Center, Cleveland, OH, USA
Department of Radiology, National Center of Neurology Diagnostic Radiography, University Hospital Cleveland
and Psychiatry, Kodaira, Japan Medical Center, Cleveland, OH, USA
 List of Contributors xiii

Reza Hayeri Jyotsna Kochiyil

Department of Radiology, Mercy Catholic Medical Center, Mount Sinai Medical Center, Miami Beach, FL, USA
Darby, PA, USA
Anton Kondakov
Meisam Hoseinyazdi Central Clinical Hospital of the Russian Academy of
Shiraz University of Medical Sciences, Shiraz, Iran Sciences, Nuclear Medicine Department, Moscow, Russia
Department of Radiology, Namazi Hospital, Shiraz, Iran Pirogov Russian National Research Medical University,
Department of Radiology and Radiation Therapy,
Peter Hu Moscow, Russia
Department of Radiology, Keck School of Medicine,
University of Southern California, Los Angeles, CA, USA Soheil Kooraki
Department of Molecular and Medical Pharmacology,
Hossein Jadvar David Geffen School of Medicine at UCLA, University of
Professor of Radiology, Urology, and Biomedical California, Los Angeles, CA, USA
Engineering, Keck School of Medicine and Viterbi School
of Engineering, University of Southern California, Los Pierluca Lanzi
Angeles, CA, USA Dipartimento di Elettronica, Informazione e
Bioingegneria, Politecnico di Milano, Milano, Italy
Sean K. Johnston
Dorian M. Lapalma
Department of Radiology, Division of Emergency
Department of Radiology, University of Southern
Radiology, Keck School of Medicine of USC, LAC+USC
California, Los Angeles, CA, USA
Medical Center, Los Angeles, CA, USA
Keck School of Medicine, University of Southern
California, Los Angeles, CA, USA
Prathamesh V. Joshi
Department of Nuclear Medicine & PET-CT,
Mykol Larvie
Kamalnayan Bajaj Hospital, Aurangabad,
Department of Radiology, Cleveland Clinic, Cleveland,
Maharashtra, India
OH, USA
Radiation Medicine Centre, Bhabha Atomic Research
Centre, Tata Memorial Centre Annexe, Parel, Mumbai,
Riccardo Laudicella
Maharashtra, India
Department of Biomedical Sciences and Morphological
and Functional Imaging, Nuclear Medicine Unit,
Peter Henry Joyce
University of Messina, Messina, Italy
Department of Radiology, Keck School of Medicine,
University of Southern California, Los Angeles, CA, USA
Christopher Lee
Keck School of Medicine of USC, HCCII Lower Level
Sanaz Katal Radiology, Los Angeles, CA, USA
Nuclear Medicine Fellow, Medical Imaging Department,
St Vincent’s Hospital Melbourne, Australia Mario Leporace
Department of Nuclear Medicine and Theranostics,
Sonya Khan “Mariano Santo” Hospital, Cosenza, Italy
Los Angeles and Veterans Administration, Greater Los
Angeles Healthcare Systems, University of California, Los Alessandro Giaj Levra
Angeles, CA, USA IRCCS Humanitas Research Hospital, Milan, Italy

Yukio Kimura Daniele Loiacono

Department of Radiology, National Center of Neurology Dipartimento di Elettronica, Informazione e
and Psychiatry, Kodaira, Japan Bioingegneria, Politecnico di Milano, Milano, Italy

Margarita Kirienko Elettra Lomeo

Department of Nuclear Medicine, Istituto Nazionale per IRCCS Humanitas Research Hospital,
lo Studio e la Cura dei Tumori, Milano, Italy Milan, Italy
xiv List of Contributors

Leda Lorenzon Erik Mittra

Department of Medical Physics, Central Hospital of Department of Diagnostic Radiology, Division of Nuclear
Bolzano, Bolzano, Italy Medicine & Molecular Imaging, Oregon Health & Science
University, Portland, OR, USA
Charito Love
Radiology, Albert Einstein College of Medicine, Farshad Moradi
Bronx, NY, USA Department of Radiology, Division of Nuclear Medicine,
Stanford, CA, USA
Reyhaneh Manafi-Farid
Research Center for Nuclear Medicine, Shariati Hospital, Russell H. Morgan
Tehran University of Medical Sciences, Department of Radiology and Radiological Science, Johns
Tehran, Iran Hopkins Medical Institution, Baltimore, MD, USA

C. Mantarro Sergey Morozov

Department of Biomedical Sciences and Morphological Chief innovation officer, Osimis S.A., Belgium
and Functional Imaging, Nuclear Medicine Unit,
University of Messina, Messina, Italy
Shabnam Mortazavi
Radiology, David Geffen School of Medicine at UCLA,
Fahad Marafi
Los Angeles, CA, USA
Jaber Al-Ahmad Center for Molecular Imaging, Kuwait
City, Kuwait
Saeideh Najafi
Department of Radiology, Keck School of Medicine,
Giuliano Mariani
University of Southern California, Los Angeles, CA, USA
Regional Center of Nuclear Medicine, Department of
Translational Research and Advanced Technologies in
Medicine and Surgery, University of Pisa, Pisa, Italy Emanuele Neri
Diagnostic and Interventional Radiology, Department
José Pablo Martín Molina of Translational Research and Advanced Technologies
Department of Radiology, San Cecilio University Hospital, in Medicine and Surgery, University of Pisa,
University of Granada, Granada, Spain Pisa, Italy

George R. Matcuk, Jr. Marco Pagan

Department of Imaging, Cedars-Sinai Medical Center, Los Nuclear Medicine, Cristo Re Hospital, Rome, Italy
Angeles, CA, USA
Christopher J. Palestro
Hiroshi Matsuda Radiology, Donald & Barbara Zucker School of Medicine
Integrative Brain Imaging Center, National Center of at Hofstra/Northwell, Hempstead, NY, USA
Neurology and Psychiatry, Kodaira, Japan Nuclear Medicine & Molecular Imaging, Northwell
Health, New Hyde Park, NY, USA
Federica Menegatti
Nuclear Medicine Unit, Department of Medicine, Ashwin Singh Parihar
University of Padua, Padua, Italy Department of Nuclear Medicine, Postgraduate Institute
of Medical Education and Research, Chandigarh, India
Genaro López Milena Mallinckrodt Institute of Radiology, Washington
Department of Radiology, Virgen de las Nieves University University School of Medicine, St Louis, MO, USA
Hospital, University of Granada, Granada, Spain
Dakshesh B. Patel
F. Minutoli Department of Radiology, University of Southern
Department of Biomedical Sciences and Morphological California, Los Angeles, CA, USA
and Functional Imaging, Nuclear Medicine Unit, Keck School of Medicine, University of Southern
University of Messina, Messina, Italy California, Los Angeles, CA, USA
 List of Contributors xv

Alok Pawaskar Ángela Salmerón-Ruiz

Radiation Medicine Centre, Bhabha Atomic Research Department of Radiology, Virgen de las Nieves University
Centre, Tata Memorial Centre Annexe, Parel, Mumbai, Hospital, University of Granada, Granada, Spain
Maharashtra, India
Department of Nuclear Medicine & PET-CT, Fernando Ruiz Santiago
Shri Siddhivinayak Ganapati Cancer Hospital, Miraj, Department of Radiology, Virgen de las Nieves University
Maharashtra, India Hospital, University of Granada, Granada, Spain
Neuro-traumatology Hospital, Virgen de las Nieves
Doina Piciu University Hospital, School of Medicine, University of
Department of Endocrine Tumors and Nuclear Medicine, Granada, Granada, Spain
Institute of Oncology Ion Chiricuta and University of
Medicine Iuliu Hatieganu, Cluj-Napoca, Romania Noriko Sato
Department of Radiology, National Center of Neurology
Francesco Pio Ieria and Psychiatry, Kodaira, Japan
Nuclear Medicine, Cristo Re Hospital, Rome, Italy
Ahmad Shariftabrizi
Janet H. Pollard University of Iowa Carver College of Medicine,
University of Iowa Carver College of Medicine, Iowa City, IA, USA
Iowa City, IA, USA Veterans Affair Medical Center, Iowa City, IA, USA

Sonal Prasad Eshani Sheth

Berlin Experimental Radionuclide Imaging Center, Berlin, Mount Sinai Medical Center, Miami Beach, FL, USA
Germany
Department of Nuclear Medicine, Charité- Yoko Shigemoto
Universitaetsmedizin, Berlin, Germany Department of Radiology, National Center of Neurology
and Psychiatry, Kodaira, Japan
Vikas Prasad
Department of Nuclear Medicine, University Hospital, Eku Shimosegawa
Ulm, Germany Department of Molecular Imaging in Medicine, Osaka
University Graduate School of Medicine, Suita, Japan
Ameya Puranik
Department of Nuclear Medicine, Tata Memorial Martina Sollini
Hospital, Homi Bhabha National Institute (HBNI), Department of Biomedical Sciences, Humanitas
Mumbai, Maharashtra, India University, Milan, Italy
IRCCS Humanitas Research Hospital, Milan, Italy
Antonio Jesús Láinez Ramos-Bossini
Department of Radiology, Virgen de las Nieves University Stefania Antonia Sperti
Hospital, University of Granada, Granada, Spain Nuclear Medicine Unit, Department of Medicine,
University of Padua, Padua, Italy
José Luis Martín Rodríguez
Department of Radiology, San Cecilio University Hospital, Daniel Stahl
University of Granada, Granada, Spain Keck School of Medicine, University of Southern
California, Los Angeles, CA, USA
Shambo Guha Roy
Department of Radiology, Mercy Catholic Medical Center, Atsuhiko Sugiyama
Darby, PA, USA Department of Neurology, Graduate School of Medicine,
Chiba University, Chiba, Japan
Kathleen Ruchalski
Radiology, David Geffen School of Medicine at UCLA, Fumio Suzuki
Los Angeles, CA, USA Department of Radiology, National Center of Neurology
and Psychiatry, Kodaira, Japan
Sana Salehi
Department of Radiology, Keck School of Medicine, Girolamo Tartaglione
University of Southern California, Los Angeles, CA, USA Nuclear Medicine, Cristo Re Hospital, Rome, Italy
xvi List of Contributors

Tommaso Tartaglione Bilge Volkan-Salanci

Radiology, IDI-IRCCS, Rome, Italy Department of Nuclear Medicine, Hacettepe University
Faculty of Medicine, Ankara, Turkey
Rosanna Tavolaro
Department of Nuclear Medicine and Theranostics, Daria Volpe
“Mariano Santo” Hospital, Cosenza, Italy Department of Biomedical Sciences, Humanitas
University, Milan, Italy
Salar Tofighi IRCCS Humanitas Research Hospital,
Department of Radiology, Keck School of Medicine, Milan, Italy
University of Southern California, Los Angeles, CA, USA
Jan Wartenberg
Laura Vendramin Department of Nuclear Medicine, Inselspital,
Nuclear Medicine Unit, Department of Medicine, University Hospital Bern, Switzerland
University of Padua, Padua, Italy

Giuseppe Visconti
Plastic Surgery, Lymphedema Center, A. Gemelli Hospital,
Sacro Cuore Catholic University, Rome, Italy
 xvii

Preface

Medical imaging has come a long way since the discovery diagnostic radiology and nuclear medicine, addressing all
of X-rays by Wilhelm Rontgen, for which he received the major organ systems and major diseases (cardiovascular,
Nobel Prize in 1901. For over a century, medical imaging neurologic, oncologic, infection, and inflammation, in
has evolved remarkably with discoveries and the develop- both adults and children). In all chapters, there is emphasis
ment of innovative technologies which in combination on correlative imaging and how one imaging modality
with major strides in understanding the biology of health complements another in a synergistic way. As appropriate,
and disease have contributed significantly to the concept of the reader is introduced to the relevant anatomy and physi-
precision health and precision medicine. These milestones ology. Modern topics of radiomics, AI/DL, and theranos-
include, but are not limited to, the discovery of radioactiv- tics are discussed. This image-rich book will appeal to
ity and positron and technical developments of the radi- physicians, allied healthcare professionals, and trainees
otracer concept, cyclotron, computed tomography (CT), (medical students, residents, fellows). The editors regret
ultrasonography (US), magnetic resonance imaging (MRI), any potential errors and omissions and commit to remedy
single photon computed tomography (SPECT), and posi- any shortcomings in any future editions.
tron emission tomography (PET). Advances in computer We dedicate this book to the memory of Sanjiv “Sam”
technology have also provided opportunities for sophisti- Gambhir, MD, PhD, Chair of Radiology at Stanford
cated incorporation of radiomics, artificial intelligence, University. Sam was our mentor, friend, and colleague. He
and deep learning (AI/DL) algorithms in medical imaging. was larger than life with deep intellect, contagious gener-
Over the past decade, it has become clear that hybrid imag- osity, and remarkable humility. The entire scientific com-
ing (e.g. PET/CT, PET/MRI, SPECT/CT) provides a broader munity and indeed humanity itself lost a glorious soul
view of disease that was unavailable previously. For exam- from his untimely passing in July 2020.
ple, it is now recognized that a small lymph node may har-
bor a tumor while a large lymph node may be benign. Ali Gholamrezanezhad
Another example is visualization of tumor infiltration in Clinical Radiology, University of Southern California,
marrow space without concordant structural abnormali- Los Angeles, CA, USA
ties. Such comprehensive information provides opportuni-
Majid Assadi
ties for enhanced imaging assessment of the patient, which
Nuclear Medicine, Bushehr University of Medical
has been demonstrated to impact clinical management and
Sciences, Bushehr, Iran
improve patient outcome.
The editors of this book have assembled an international Hossein Jadvar
team of expert imaging specialists to compile comprehen- Radiology, Urology, and Biomedical Engineering,
sive coverage of correlative imaging in the domains of University of Southern California, Los Angeles, CA, USA
 1

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 imaging. Table 1.1 provides a brief review of the different

tomographic imaging modalities which form the crux of
Correlation is defined as a connection or relationship correlative imaging.
between two or more things that are not caused by Each imaging modality has its own strengths and short-
chance [1]. Medical research is naturally based on finding comings. The utilization of an individual modality depends
the relationship between the known and the unknown [2]. on multiple factors:
Correlation has been an integral part of medicine. A clini- 1) Patient-related factors: age of patient, organ of interest,
cian correlates signs and symptoms with the results of claustrophobia, contrast allergy, pregnancy etc.
medical imaging, pathology or laboratory investigations. 2) Modality-related factors: availability, radiation expo-
A nuclear medicine physician or radiologist correlates sure, resolution, need of morphological versus func-
findings of medical imaging with another imaging modal- tional information
ity or laboratory investigation such as tumor marker levels, 3) Physician-related factors: expertise of radiologist/
hormone levels etc. Correlative imaging comprises com- nuclear medicine physician or preference of referring
bining complimentary information provided by different physician
imaging techniques for better interpretation of pathology. 4) Miscellaneous: financial burden of examination, insur-
In this chapter, our aim is to familiarize readers with the ance coverage etc.
basics of correlative imaging, the strengths and shortcom-
ings of various imaging modalities, and how the correla- Depending on these multiple factors, an imaging modal-
tion among them leads to better understanding of ity is utilized as the investigation of choice during workup
pathologies. The main emphasis of this chapter will be on of a particular patient. However, it is not uncommon that
“fusion imaging”, which has proved to be the best available imaging findings are nonspecific and rather than leading to
form of correlative imaging at present. a definitive diagnosis they lead to a spectrum of differential
diagnoses. Through “fusion imaging” or “hybrid imaging”
radiologists/nuclear physicians frequently utilize correla-
Correlative Imaging tive imaging with the intent to narrow down the differentials
and/or pinpoint the diagnosis.
Medical imaging has come a long way since Roentgen first
discovered the X-ray in 1895 [3]. Today X-ray, fluoroscopy, Correlative imaging can be defined as “imaging the
computed tomography (CT), ultrasonograpy, single-photon same sample (field of view [FOV] or subject)
emission tomography (SPECT), positron emission tomog- sequentially or simultaneously with different imag-
raphy (PET), magnetic resonance imaging (MRI), PET-CT, ing modalities to obtain complimentary/additive
SPECT-CT, and PET-MRI form the gamut of medical information.”

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.
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 used tracer at present is the 18F-labeled glucose analogue
comparative imaging for many years, a typical example of fluorodeoxyglucose (FDG), and it is the workhorse of
this being the “hot spot” observed in bone scans interpreted PET-CT imaging at present.
as metastatic or degenerative based on comparing it with Though most commonly utilized in oncological imaging,
MRI or CT of the same bone. However, now fusion imaging FDG-PET has many other nononcological applications
techniques such as SPECT-CT, PET-CT, and PET-MRI have now: dementia, myocardial viability, and infection imaging
emerged as most widely accepted form of correlative imag- to name a few. Hence FDG is utilized here as example to
ing. Conventionally, SPECT and PET had been domains of demonstrate PET tracer characteristics to radiologists.
nuclear physicians while CT and MR had been the radiolo-
● Principle of FDG PET imaging
gist’s forte. With the advent and rapid success of fusion
Enhanced glucose metabolism of cancer cells (primarily
imaging there is a need for combined knowledge of both
dependent on anaerobic glycolysis or the Warburg effect)
nuclear medicine and radiology for accurate interpretation
forms the fundamental basis of FDG PET/CT imaging of
of fusion imaging findings. In the next section, we aim to
malignancies. The increased glucose utilization by the
familiarize nuclear physicians and radiologists with the
malignant cells is characterized by high expression of glu-
basic principles of tomographic techniques utilized in
cose transporters (GLUTs, namely GLUT1 and GLUT3)
correlative/fusion imaging.
and upregulation of hexokinase activity [4].
Glucose is taken up by tumor cells by facilitated transport
Positron Emission Tomography–Computed (via GLUT) and then undergoes glycolysis with the forma-
tion of pyruvate under aerobic conditions. However, under
Tomography
hypoxic conditions (such as in a necrotic tumor), glucose is
metabolized under anaerobic conditions with resultant
PET-CT: What a Radiologist Should Know about PET
increased tumor lactate levels. FDG is a radiopharmaceuti-
Basics of PET-CT cal (RP) analog of glucose that is taken up by metabolically
Positron Emission Tomography active tumor cells using facilitated transport similar to that
PET is a tomographic technique that measures the three- used by glucose (Figure 1.1). Despite the chemical differ-
dimensional distribution of positron-emitter labeled radi- ences, cellular uptake of FDG is similar to that for glucose.
otracers. PET allows noninvasive quantitative assessment of FDG passes the cellular membrane through facilitated
biochemical and functional processes. The most commonly transport mediated by the GLUTs, of which more than 14
 Introduction to Correlative Imaging 3

CELL

CYTOPLASM

hexokinase
GLUCOSE GLUCOSE GLUCOSE-6-PO4

GLUT Glusose-6-
receptors glycolysis
phosphatase

CELL
CYTOPLASM

hexokinase
F-18 FLUORODEOXYGLUCOSE FDG FDG-6-PO4
(FDG)
GLUT Glusose-6-
receptors glycolysis
phosphatase

Figure 1.1 Mechanism of FDG uptake and metabolic trapping inside the cell.

different isoforms have been identified in humans, differing urine, lymphoid tissue, bone marrow, salivary glands,
in their tissue distribution and affinity for glucose. GLUT1 and testes (Figure 1.2). Breast, uterus, ovary, and thymus
is the most common glucose transporter in humans and is, can show variable FDG uptake.
together with GLUT3, overexpressed in many tumors [5–7].
Like glucose, it undergoes phosphorylation to form FDG-6- Causes of Physiological FDG Uptake and Normal
phosphate; however, unlike glucose, it does not undergo Variants Mimicking Pathology
further metabolism. At the same time, expression of the As increased FDG uptake is not limited to malignant tis-
enzyme glucose-6-phosphatase is usually significantly sues alone, for the appropriate interpretation of FDG
decreased in the malignant cells, and FDG-6-phosphate PET-CT imaging the interpreting radiologist needs to be
thus undergoes only minimal dephosphorylation, hence aware of the physiological causes of FDG uptake as well as
becoming “metabolically trapped” in cancer cells [8]. The commonly encountered physiological variants [10–15].
distribution of FDG in normal organs and pathological Table 1.2 summarizes and enumerates the different
lesions is detected by PET scanners. physiological causes and sites of FDG uptake that can
mimic disease and the suggested interventions to reduce
● Preparation for FDG-PET and scan acquisition
them.
Patients are advised to fast and not consume beverages,
except for water, for at least 4–6 hours before the admin- ● Quantification of FDG uptake and SUV
istration of FDG to decrease physiologic glucose levels While interpreting a PET-CT scan, it is the relative tissue
and to reduce serum insulin levels to near basal levels. uptake of FDG (or any other PET RP) that is of interest to
Oral hydration with water is encouraged. Intravenous the reporting physician. Visual analysis is sufficient in
fluids containing dextrose or parenteral feedings also most cases, but the standardized uptake value (SUV) is a
should be withheld for 4–6 hours [9]. FDG is injected commonly used measure of FDG uptake and it is routinely
intravenously and the PET scan is typically acquired mentioned in PET-CT reports. The basic expression for
50–90 minutes after FDG injection. SUV is [16]
● Normal biodistribution and physiological variants
r
Physiological FDG uptake is seen in the brain, myocar- SUV
a w
dium, liver, spleen, stomach, intestines, kidneys and
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) utilized as a marker of change in the metabolic activity of
measured by the PET scanner within a region of interest pathology and hence it is important to reproduce the scan
(ROI), a is the decay-corrected amount of injected radiola- conditions during the follow-up PET-CT scan performed
beled FDG (kBq), and w is the weight of the patient (g), for response evaluation.
which is used as a surrogate for distribution volume of
tracer. If all the injected FDG is retained and uniformly dis-
What Nuclear Medicine Physicians Need
tributed throughout the body, the SUV everywhere will be
to Know about CT
1 g/ml regardless of the amount of FDG injected or patient
size [17, 18]. Commonly SUVmax of lesions (maximum PET alone is limited by poor anatomic detail, and correla-
SUV) is provided in reports, which is the SUV of most avid tion with some other form of imaging, such as CT, is desir-
voxel in ROI. able for differentiating normal from abnormal radiotracer
The reproducibility of SUV measurements depends on uptake [8]. Hence PET-CT morpho-metabolic imaging
the reproducibility of clinical protocols, for example dose emerged as an ideal single investigation for oncology prac-
infiltration, time of imaging after 18F-FDG administration, tice. However, this also mandates the nuclear physician to
type of reconstruction algorithms, type of attenuation have adequate knowledge of the CT component of imaging
maps, size of the ROI, and changes in uptake by organs as well as the various interventions employed in CT
other than the tumor [9]. SUV or SUVmax values are often acquisition.
 Introduction to Correlative Imaging 5

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 PET-CT appearance Interventions to reduce uptake

Brown adipose Nonshivering thermogenesis FDG uptake in fat density Making patients wear warm
tissue (BAT) requires glucose for glycolysis as a (−150 to −50 HU) in neck, clothing and providing a
source of adenosine triphosphate, shoulder, and paraspinal regions blanket in the waiting suite
which in turn is utilized in fatty (Figure 1.3) to avoid cold-induced BAT
acid oxidation activation.
Less common in perirenal,
BAT is innervated by the perigastric regions Premedication with
sympathetic nervous system and beta-blockers or diazepam
expresses beta-adrenergic receptors, FDG uptake in BAT is more
which are stimulated by cold common in younger patients,
females > males
Vocal cords Phonation-related laryngeal muscle Symmetrically increased FDG If the region of interest is the
contraction uptake in both vocal cords larynx, the patient should be
(Figure 1.4) instructed to avoid talking
after FDG injection
Myocardium Glucose as substrate for energy Variable, focal or diffuse without Fasting before FDG PET-CT
(GLUT1 and insulin-sensitive corresponding morphologic (4–12 hours)
GLUT4) abnormality on CT High-fat, low-carbohydrate
diet before scan
Premedication with
unfractionated heparin
before FDG injection
Thymus Physiological uptake in pediatric Inverted V-shaped/butterfly pattern The uptake has a diffuse
patients (especially in of anterior mediastinal uptake on characteristic pattern: no
postchemotherapy setting, known the transaxial view and absence of specific intervention
as “thymic rebound”) lesion on corresponding CT
(Figure 1.5)
Lactating Due to secretory hyperplasia and Bilateral breast reveal diffuse FDG The uptake has a diffuse
breasts the increased expression of GLUT-1 uptake, but if infant is suckling characteristic pattern: no
unilateral breast only that side can specific intervention
show diffuse FDG uptake
(Figure 1.6)
Urinary system FDG excretion in urine Usually does not affect scan Dual point/delayed postvoid
interpretation imaging with or without
Focal retention in kidneys/ureter/ diuretic intervention
urinary bladder can mimic
pathology
Ovary FDG uptake in corpus luteal cyst Ovoid FDG uptake with smooth Correlation with menstrual
margins or a rim of FDG uptake history
with a photopenic center
(Figure 1.7)
Endometrium FDG in menstrual flow FDG uptake in endometrium in a If being evaluated for
diffuse uniform pattern gynecological pathology,
(Figure 1.8) PET-CT scan should be
scheduled in the
postmenstrual phase
Colon Related to bowel motility Typically heterogeneous and can Uptake pattern: no
The uptake in cecum and right vary in distribution from mild focal interventions
colon could be result of higher to diffuse uptake
lymphocytes in these regions Often, there is higher uptake
within the cecum and right colon
(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 physiological FDG uptake is
the artery of Adamkiewicz, which visualized in the cervical spinal
originates on the left side of the cord peaking at C4 level, and in the
aorta between the T9 and T11 lower thoracic spinal cord peaking
vertebral segments at the T11–T12 segments
Increased cross-sectional area of (Figure 1.9)
the spinal cord
Skeletal Exercise induces glucose uptake in If related to exercise, usually Patients should avoid
muscles skeletal muscles symmetrical FDG uptake in strenuous exercise for
Labored breathing can increase muscles with no abnormal 48–72 hours before
FDG uptake in intercostal muscles enhancement or lesion on CT scheduled scan
and diaphragm If related to meal/insulin diffuse Fasting status should be
In postmeal state, insulin increases FDG uptake in skeletal muscles confirmed before FDG
GLUT (GLUT-4) mediated skeletal (usually also accompanied with injection
muscle glucose uptake 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.
 Introduction to Correlative Imaging 7

(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) 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].
Figure 1.5 (a) MIP image of PET-CT of a 10-year-old boy The ability of matter to attenuate X-rays is measured in
showing physiological FDG uptake in the thymus (black arrows). Hounsfield units (HU). By definition, water is assigned a
(b) Hypermetabolism in the soft tissue neoplasm in the occipital
density value of 0 HU and air a value of −1000 HU.
region (red arrow).
Attenuation values for most soft tissues fall within
30–100 HU. Notable exceptions are lungs, with attenuation
Computed Tomography
values approaching −1000 HU (due to high air content),
Although the potential applications of X-rays in medical and mineralized tissues such as bone, with attenuation val-
imaging diagnosis were clear from the beginning, the ues of approximately 1000 HU [21].
implementation of the first X-ray CT system was made in
1972 by Godfrey Newbold Hounsfield (Nobel prize winner
Intravenous and Oral Contrast in CT Scanning
in 1979 for Physiology and Medicine), who constructed the
prototype of the first medical CT scanner and is considered Intravenous Contrast
the father of CT. After this, CT was immediately welcomed Differences in the CT attenuation of healthy tissue
by the medical community and has often been referred to 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

Depending on the ROI, gastrointestinal luminal contrast
Figure 1.11 Basic principles of a CT scan. 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-
(i.e. greater signal-to-noise and contrast to noise ratios) and tion and less commonly by the rectal enema route for
hence facilitate detection of abnormality. Hence, contrast evaluation of colonic pathologies.
imaging agents are often used for better visualization of the It should be noted that the contrast agents alter the atten-
tissue of interest by CT [21, 22]. uation caused by tissues and hence result in overestima-
Today, a wide range of ionic and nonionic contrast agents tion of SUV values used in PET quantification (more so
is available and effective diagnostic dose of a contrast agent 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 Efforts have been made to minimize such image degra-
dation by the generation of a respiratory motion cor-
Recent PET-CT scanners allow excellent fusion of the PET rected or four-dimensional PET-CT during which the
and CT images and thus improve lesion localization and PET data are acquired in synchronization with respira-
interpretation accuracy. Moreover, the employment of the tory motion [30].
CT data for attenuation correction has led to high patient 2) Attenuation correction artifacts: The presence of high-
throughput [29]. Although PET-CT imaging offers many density material in the patient’s body either in the form
advantages, this dual-modality imaging also poses some of high-density material like bone cement or venous
technical challenges due to a few artifacts. The reader inter- pooling of intravenous contrast/barium from previous
preting PET-CT scans needs to be aware of these limitations. studies in bowel loops can result in artifactual FDG
The artifacts can be broadly divided into following uptake due to exaggerated attenuation correction at
categories: these sites. A clinical example is shown in Figure 1.16.
3) Beam hardening artifact: This artifact appears as multiple
1) Motion artifacts (respiratory or patient related): Although linear bands of abnormal attenuation traversing a body
the CT and PET acquisitions are performed without part adjacent to high-attenuation objects, such as metal
changing the patient position, voluntary or involuntary prosthesis, dental fillings, chemo ports, and pacemakers.
movements of patient can result in misregistration of Patients need to be instructed to remove metallic objects
PET and CT images. Most commonly such misregistra- before scan acquisition and a note should be made of
tion artifacts are observed in lesions of the lungs and fixed/in situ metallic prosthesis/implants. An example is
liver. An example is shown in Figure 1.15. 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- with arms down, such as in the case of head and neck
tion correction factors. malignancy. When a patient extends beyond the CT FOV,
A similar artifact can be seen when the PET-CT scan is the extended part of the anatomy is truncated and conse-
acquired with the hands on the sides of the trunk and quently is not represented in the reconstructed CT image.
hence the easiest way to prevent this artifact is to per- Truncation also produces streaking artifacts at the edge
form the scan with arms up or down, depending on of the CT image, resulting in an overestimation of the
clinical indication. attenuation coefficients used to correct the PET data.
4) Truncation artifact: Truncation artifacts in PET-CT are This increase in attenuation coefficients creates a rim of
due to the difference in size of the FOV between the CT high activity at the truncation edge (see the example in
(50 cm) and PET (70 cm) tomographs [31]. These artifacts Figure 1.18), potentially resulting in misinterpretation of
are frequently seen in large patients or patients scanned 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 chyma (see the example in Figure 1.19). Such uptake
the center of the FOV and with arms above the head to can be the result of iatrogenic FDG micro-embolus at
reduce truncation artifacts [29]. the time of injection [33] and when such a finding can
5) Radiopharmaceutical related: Although relatively rare, affect management of a patient, a follow-up scan can
focal FDG uptake (or other PET radiotracer uptake) be performed to avoid false-positive interpretation. In
without any CT demonstrable lesion needs to be the next section, few clinical case examples present
interpreted with caution, especially in lung paren- (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

Although 18-F-FDG is the most widely used tracer in
The following section consists of the pictorial demon- fusion imaging in the form of PET-CT, many other RPs
stration of clinical case examples (Figures 1.20–1.22) have made a significant impact in patient management and
where fusion imaging of FDG PET and CT resulted in have become part of routine patient management. The list
accurate diagnosis of pathology and its extent that would of such RPs is exhaustive and beyond the scope of this
have been otherwise difficult to reach. 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 recurrence, staging high-risk cases, and
(small-molecule PSMA inhibitors) treatment planning for peptide receptor
radioligand therapy
Gallium-68 DOTANOC/ Binding with somatostatin receptors Neuroendocrine tumor imaging and
DOTATOC/DOTATATE (DOTA- expressed in neuroendocrine tumor cells treatment planning for peptide receptor
conjugated peptides) radionuclide therapy
Fluorine-18 fluoro-dopamine Analog of l-DOPA, to trace the Evaluation of movement disorders
dopaminergic pathway and to evaluate Evaluation of congenital hyperinsulinemia
striatal dopaminergic presynaptic function
18
Fluorine-18 sodium fluoride F is substituted for hydroxyl groups in Diagnosis of skeletal metastases
hydroxyapatite and covalently bonds to
the surface of new bone

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
Gamma camera (Figure 1.26) has been in use for getting
functional information on the physiological, biochemical,
Introduction
and metabolic processes in the various organs in the body.
Among the fusion or correlative imaging modalities, The tracer used in gamma camera imaging is usually spe-
PET-CT is the often discussed modality, mainly due to its cifically targeted to obtain information from a particular
widespread clinical and research applications, although we organ system. Hence, once administered into the patient’s
must emphasize the potential and increasing applications body, the tracer accumulates in the target organ system.
of SPECT–CT, which is often underestimated and may be 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.
 Introduction to Correlative Imaging 19

Figure 1.26 Schematic representation of gamma

camera.
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)

the target organ may be collected about a particular patho- i) Combined SPECT-CT images have the best of both
physiological process. However, at the same time, what- worlds. They have all the anatomical information lack-
ever little morphological information is obtained by ing in SPECT images and functional information lack-
background tracer activity diminishes significantly. Hence ing in CT images. CT also helps in proper localization
nuclear medicine techniques often lack anatomical land- of tracer uptake to ultimately help in correct diagnosis
marks. Also, there is definite loss of data in the planar and treatment.
imaging due to the attenuation of gamma rays coming ii) Not only this, CT attenuation maps are used for
from organs deep inside the body. attenuation correction and this improves the quality
SPECT entails 3D reconstruction of tracer distribution of SPECT images. There are many applications of
within the patient body with the help of data collected by SPECT-CT that are well established clinically. As
rotating detectors around the patient body. This helps to new advanced systems are becoming widely available,
achieve better anatomical information, for example in further improving the accuracy of image fusion and
the case of bone scan or myocardial perfusion imaging. shortening acquisition times, the newer applications
CT scanning, on the other hand, is a 3D reconstruction of are becoming more evident. Apart from applications
X-ray attenuation value maps providing morphological in oncology, interesting uses of SPECT-CT are seen
details like size, shape, and location. Use of contrast in the areas of minimally invasive surgery and cardi-
agent in CT primarily provides information about perfu- ology. We shall start our treatise with some technical
sion and the changes in perfusion pattern occurring in information about these systems before going into
various disease processes. However, CT often does not the clinical applications.
provide any information on the functional or metabolic
status of organs in the body. Many disease processes
show pathophysiological changes much before morpho- SPECT–CT System Information
logical changes are manifested. Also, in presence of ana-
tomical distortions secondary to various treatments, Combining SPECT and CT images acquired from differ-
anatomical imaging interpretations are difficult and ent standalone machines has often been challenging. This
often uncertain because of changes in symmetry and per- is because usually the studies are acquired on different
fusion pattern. dates, on different machines by different operators using
Hence it is of vital importance to understand that different protocols. This creates differences in the posi-
nuclear medicine (SPECT) and anatomical imaging (CT) tion of the patient body, extremities as well as spinal cur-
are not competitive to each other, but in fact complimen- vatures, as table positions may differ with different
tary in nature. The fundamental advantages of this are as systems. Furthermore, it is not possible to match respira-
follows: 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 form at the very beginning of emission and transmission
fusion techniques have been developed which can regis- CT, most notably the work by Kuhl, Hale, and Eaton, who
ter and fuse images from multiple sources [39, 40], but obtained the first trans-axial transmission CT scan of a
they are best suited for correlating images from rigid struc- patient’s thorax using their Mark II brain SPECT scanner
tures such as the brain [41] and skeleton [42, 43]. However, in the mid-1960s [50]. However, use of transmission imag-
for thorax and abdomen, due to inherent movement of ing with an external radionuclide transmission source was
internal organs, software fusion has remained challeng- introduced for attenuation correction in SPECT [51, 52]
ing. Data sets from two fundamentally different imaging and PET [53, 54] only in the 1980s. In this system, external
modalities with different spatial resolution and with few transmission scanning was used with SPECT to perform
common landmarks make it further complicated. A sys- both attenuation correction and anatomical localization.
tem offering same geometry for acquisition of SPECT and However, a transmission scan provides poor quality
CT images almost simultaneously, such as SPECT-CT anatomical details and contrast resolution, hence these
scanning, offers much better data sets for fusion. Here the systems never grew into routine applications. Over the last
patient remains on the same table and in the same posi- decade or so, combined SPECT-CT scanners have become
tion while undergoing SPECT and CT acquisitions sepa- commercially available which acquire data from SPECT
rated by a few minutes. and CT on the same gantry. The patient remains in same
The practical advantages of SPECT-CT fusion imaging position and on the same table, which is then sequentially
are multifold: moved from one modality to another. The final data
acquired is then transferred to a single computer which
i) These systems are able to superimpose functional
does data correction, image reconstruction, integration,
information from nuclear medicine data sets onto ana-
and display and allows analysis for better diagnosis.
tomical information from CT scans, greatly improving
The early SPECT-CT systems tried simultaneous acqui-
the confidence of the reporting diagnostician.
sition of SPECT and CT data [55, 56], but the problem
ii) These systems are able to facilitate attenuation correc-
with a simultaneous SPECT-CT acquisition system was in
tion of SPECT data with patient-specific attenuation
designing a common detector with sufficient temporal
maps acquired from CT [44, 45]. Because of this, there
and energy resolution to discriminate the primary radio-
is improvement in the spatial resolution, contrast, and
nuclide photons from both the X-ray signal and the scat-
signal-to-noise ratio of the image.
ter of the radionuclide photons. This problem remains
iii) There is improvement in the functional data quality
unsolved. The “modern” SPECT-CT system was originally
aided by CT, which shows great promise in quantifica-
developed by Hasegawa et al. at the University of
tion of RP uptake [46, 47]. This is very useful for (i)
California, San Francisco in the mid-1990s [45]. These
better radiation dosimetry [48, 49] and (ii) monitoring
systems have SPECT and CT gantries in tandem (in-line)
response to therapy.
which can acquire patient data sequentially and send it to
The concept of combining structural and functional the same computer for further fusion and processing
information was conceived and implemented in prototype (Figure 1.27).

SPECT-CT gantry

Patient table SPECT detectors CT

Figure 1.27 Schematic diagram of the modern SPECT-CT system.

Another random document with
no related content on Scribd:
advanced on all sides from the plantations, and nothing but a small
open space divided the people from each other, Sir George directed
them to halt, and, after thanking them for what they had done, he
requested them to rest themselves on the grass till refreshments
could be brought from the Hermitage, after partaking of which they
had best move homewards, as it seemed in vain to attempt anything
more till next day. He then took leave of them, and hurried home to
the Hermitage, from whence a number of people were soon seen
returning with the promised refreshments.
Having finished what was set before them, and sufficiently rested
themselves, most of them departed, having first declared their
readiness to turn out the moment they were wanted. But when his
friends proposed to David Williams his returning home, he resolutely
refused, declaring his determination to continue his search the whole
night; and the poor man’s distress seemed so great, that a number of
the people agreed to accompany him. Robert, on being applied to,
furnished them, from the Hermitage, with a quantity of torches and
lanterns; and the people themselves, having got others from the
cottages in the neighbourhood, divided into bands, and, fixing on
John Maxwell’s house for intelligence to be sent to, parted in
different ways on their search.
At first all were extremely active, and no place the least suspicious
was passed by; but as the night advanced their exertions evidently
flagged, and many of them began to whisper to each other that it was
in vain to expect doing any good in the midst of darkness; and, as the
idea gained ground, the people gradually separated from each other,
and returned to their homes, promising to be ready early in the
morning to renew the search.
“An’ now, David,” said John Maxwell, “let’s be gaun on.”
“No to my house,” cried David;—“not to my ain house. I canna face
Matty, and them no found yet.”
“Aweel, then,” said John, “suppose ye gang hame wi’ me, and fling
yersel down for a wee; an’ then we’ll be ready to start again at gray
daylight.”
“An’ what will Matty think in the meantime?” answered David.
“But gang on, gang on, however,” he added, “an’ I’se follow ye.”
 John Maxwell, glad that he had got him this length, now led the
way, occasionally making a remark to David, which was very briefly
answered, so that John, seeing him in that mood, gave up speaking
to him, till, coming at length to a bad step, and warning David of it,
to which he got no answer, he hastily turned round and found that he
was gone. He immediately went back, calling to David as loud as he
could, but all to no purpose. It then occurred to him that David had
probably changed his mind, and had gone homewards; and, at any
rate, if he had taken another direction, that it was in vain for him to
attempt following him, the light he carried being now nearly burnt
out. He therefore made the best of his way to his own house.
In the meantime, poor David Williams, who could neither endure
the thought of going to his own house nor to his brother-in-law’s,
and had purposely given him the slip, continued to wander up and
down without well knowing where he was, or where he was going to,
when he suddenly found himself, on coming out of the wood, close to
the cottage inhabited by a widow named Elie Anderson.
“I wad gie the world for a drink o’ water,” said he to himself; “but
the puir creature will hae lain down lang syne, an’ I’m sweer to
disturb her;” and as he said this, he listened at the door, and tried to
see in at the window, but he could neither see nor hear anything, and
was turning to go away, when he thought he saw something like the
reflection of a light from a hole in the wall, on a tree which was
opposite. It was too high for him to get at it without something to
stand upon; but after searching about, he got part of an old hen-
coop, and placing it to the side of the house, he mounted quietly on
it. He now applied his eye to the hole where the light came through,
and the first sight which met his horrified gaze was the body of his
eldest daughter, lying on a table quite dead,—a large incision down
her breast, and another across it!
David Williams could not tell how he forced his way into the
house; but he remembered bolts and bars crashing before him,—his
seizing Elie Anderson, and dashing her from him with all his might;
and that he was standing gazing on his murdered child when two
young ones put out their hands from beneath the bed-clothes.
“There’s faither,” said the one.
“Oh, faither, faither,” said the other, “but I’m glad ye’re come, for
Nanny’s been crying sair, sair, an’ she’s a’ bluiding.”
 David pressed them to his heart in a perfect agony, then catching
them up in his arms, he rushed like a maniac from the place, and
soon afterwards burst into John Maxwell’s cottage,—his face pale, his
eye wild, and gasping for breath.
“God be praised,” cried John Maxwell, “the bairns are found! But
where’s Nanny?”
Poor David tried to speak, but could not articulate a word.
“Maybe ye couldna carry them a’?” said John; “but tell me whaur
Nanny is, and I’se set out for her momently.”
“Ye needna, John, ye needna,” said David; “it’s ower late, it’s ower
late!”
“How sae? how sae?” cried John; “surely naething mischancy has
happened to the lassie?”
“John,” said David, “grasping his hand, she’s murdered—my
bairn’s murdered, John!”
“Gude preserve us a’,” cried John; “an’ wha’s dune it?”
“Elie Anderson,” answered David; “the poor innocent lies yonder a’
cut to bits;” and the unhappy man broke into a passion of tears.
John Maxwell darted off to Saunders Wilson’s. “Rise, Saunders!”
cried he, thundering at the door; “haste ye and rise!”
“What’s the matter now?” said Saunders.
“Elie Anderson’s murdered David’s Nanny; sae haste ye, rise, and
yoke your cart, that we may tak her to the towbuith.”
Up jumped Saunders Wilson, and up jumped his wife and his
weans, and in a few minutes the story was spread like wildfire. Many
a man had lain down so weary with the long search they had made,
that nothing they thought would have tempted them to rise again;
but now they and their families sprung from their beds, and hurried,
many of them only half-dressed, to John Maxwell’s, scarcely
believing that the story could be true. Amongst the first came
Geordie Turnbull, who proposed that a number of them should set
off immediately, without waiting till Saunders Wilson was ready, as
Elie Anderson might abscond in the meantime; and away he went,
followed by about a dozen of the most active. They soon reached her
habitation, where they found the door open and a light burning.
 “Ay, ay,” said Geordie, “she’s aff, nae doubt, but we’ll get her yet.
Na, faith,” cried he, entering, “she’s here still; but, gudesake, what a
sight’s this!” continued he, gazing on the slaughtered child. The
others now entered, and seemed filled with horror at what they saw.
“Haste ye,” cried Geordie, “and fling a sheet or something ower
her, that we mayna lose our wits a’thegither. And now, ye wretch,”
turning to Elie Anderson, “your life shall answer for this infernal
deed. Here,” continued he, “bring ropes and tie her, and whenever
Saunders comes up, we’ll off wi’ her to the towbuith.”
Ropes were soon got, and she was tied roughly enough, and then
thrown carelessly into the cart; but notwithstanding the pain
occasioned by her thigh-bone being broken by the force with which
David Williams dashed her to the ground, she answered not one
word to all their threats and reproaches, till the cart coming on some
very uneven ground, occasioned her such exquisite pain, that, losing
all command over herself, she broke out into such a torrent of abuse
against those who surrounded her, that Geordie Turnbull would have
killed her on the spot, had they not prevented him by main force.
Shortly afterwards they arrived at the prison; and having delivered
her to the jailor, with many strict charges to keep her safe, they
immediately returned to assist in the search for the bodies of the
other children, who, they had no doubt, would be found in or about
her house.
When they arrived there, they found an immense crowd
assembled, for the story had spread everywhere; and all who had lost
children, accompanied by their friends and neighbours and
acquaintances, had repaired to the spot, and had already commenced
digging and searching all round. After working in this way for a long
while, without any discovery being made, it was at length proposed
to give up the search and return home, when Robin Galt, who was a
mason, and who had been repeatedly pacing the ground from the
kitchen to the pig-sty, and from the pig-sty to the kitchen, said,
“Frien’s, I’ve been considering, and I canna help thinking that there
maun be a space no discovered atween the sty and the kitchen, an’
I’m unco fond to hae that ascertained.”
“We’ll sune settle that,” says Geordie Turnbull. “Whereabouts
should it be?”
 “Just there, I think,” says Robin.
Geordie immediately drove a stone or two out, so that he could get
his hand in.
“Does onybody see my hand frae the kitchen?” asked he.
“No a bit o’t,” was the answer.
“Nor frae the sty?”
“Nor frae that either.”
“Then there maun be a space, sure enough,” cried Geordie,
drawing out one stone after another, till he had made a large hole in
the wall. “An’ now,” said he, “gie me a light;” and he shoved in a
lantern, and looked into the place. “The Lord preserve us a’!” cried
he, starting back.
“What is’t—what is’t?” cried the people, pressing forward on all
sides.
“Look an’ see!—look an’ see!” he answered; “they’re a there—a’ the
murdered weans are there, lying in a raw!”
The wall was torn down in a moment; and, as he had said, the
bodies of the poor innocents were found laid side by side together.
Those who entered first gazed on the horrid scene without speaking,
and then proceeded to carry out the bodies, and to lay them on the
green before the house. It was then that the grief of the unhappy
parents broke forth; and their cries and lamentations, as they
recognised their murdered little ones, roused the passions of the
crowd to absolute frenzy.
“Hanging’s ower gude for her,” cried one.
“Let’s rive her to coupens,” exclaimed another.
A universal shout was the answer; and immediately the greater
part of them set off for the prison, their numbers increasing as they
ran, and all burning with fury against the unhappy author of so much
misery.
The wretched woman was at this moment sitting with an old crony
who had been admitted to see her, and to whom she was confessing
what had influenced her in acting as she had done.
“Ye ken,” said she, “I haena jist been mysel since a rascal that had
a grudge at me put aboot a story of my having made awa wi’ John
Anderson, wi’ the help o’ arsenic. I was ta’en up and examined aboot
it, and afterwards tried for it, and though I was acquitted, the
neebours aye looked on me wi’ an evil eye, and avoided me. This
drave me to drinking and other bad courses, and it ended in my
leaving that part of the kintra, and coming here. But the thing
rankled in my mind, and many a time hae I sat thinkin’ on it, till I
scarcely kent where I was, or what I was doing. Weel, ae day, as I was
sitting at the roadside, near the Hermitage, and very low about it, I
heard a voice say, ‘Are you thinking on John Anderson, Elie? Ay,
woman,’ said Charlotte Beaumont, for it was her, ‘what a shame in
you to poison your own gudeman!’ and she pointed her finger, and
hissed at me. When I heard that,” continued Elie, “the whole blood in
my body seemed to flee up to my face, an’ my very een were like to
start frae my head; an’ I believe I wad hae killed her on the spot,
hadna ane o’ Sir George’s servants come up at the time; sae I sat
mysel doun again, an’ after a lang while, I reasoned mysel, as I
thought, into the notion that I shouldna mind what a bairn said; but
I hadna forgotten’t for a’ that.
“Weel, ae day that I met wi’ her near the wood, I tell’t her that it
wasna right in her to speak yon gate, an’ didna mean to say ony mair,
hadna the lassie gane on ten times waur nor she had done before,
and sae angered me, that I gied her a wee bit shake, and then she
threatened me wi’ what her faither wad do, and misca’ed me sae sair,
that I struck her, and my passion being ance up, I gaed on striking
her till I killed her outright. I didna ken for a while that she was
dead; but when I found that it was really sae, I had sense enough left
to row her in my apron, an’ to tak her hame wi’ me; an’ when I had
barred the door, I laid her body on a chair, and sat down on my
knees beside it, an’ grat an’ wrung my hands a’ night lang.
“Then I began to think what would be done to me if it was found
out; an’ thought o’ pittin’ her into a cunning place, which the man
who had the house before me, and who was a great poacher, had
contrived to hide his game in; and when that was done, I was a
thought easier, though I couldna forgie mysel for what I had done,
till it cam into my head that it had been the means o’ saving her frae
sin, and frae haein’ muckle to answer for; an’ this thought made me
unco happy. At last I began to think that it would be right to save
mair o’ them, and that it would atone for a’ my former sins; an’ this
took sic a hold o’ me, that I was aye on the watch to get some ane or
ither o’ them by themselves, to dedicate them to their Maker, by
marking their bodies wi’ the holy cross:—but oh!” she groaned, “if I
hae been wrang in a’ this!”
The sound of the people rushing towards the prison was now
distinctly heard; and both at once seemed to apprehend their object.
“Is there no way of escape, Elie,” asked her friend, wringing her
hands.
Elie pointed to her broken thigh, and shook her head. “Besides,”
said she, “I know my hour is come.”
The mob had now reached the prison, and immediately burst open
the doors. Ascending to the room where Elie was confined, they
seized her by the hair, and dragged her furiously downstairs. They
then hurried her to the river, and, with the bitterest curses, plunged
her into the stream; but their intention was not so soon
accomplished as they had expected; and one of the party having
exclaimed that a witch would not drown, it was suggested, and
unanimously agreed to, to burn her. A fire was instantly lighted by
the waterside, and when they thought it was sufficiently kindled, they
threw her into the midst of it. For some time her wet clothes
protected her, but when the fire began to scorch her, she made a
strong exertion, and rolled herself off. She was immediately seized
and thrown on again; but having again succeeded in rolling herself
off, the mob became furious, and called for more wood for the fire;
and by stirring it on all hands, they raised it into a tremendous blaze.
Some of the most active now hastened to lay hold of the poor wretch,
and to toss her into it; but in their hurry one of them having trod on
her broken limb, caused her such excessive pain, that when Geordie
Turnbull stooped to assist in lifting her head, she suddenly caught
him by the thumb with her teeth, and held him so fast, that he found
it impossible to extricate it. She was therefore laid down again, and
in many ways tried to force open her mouth, but without other effect
than increasing Geordie’s agony; till at length one of them seizing a
pointed stick from the fire, and thrusting it into an aperture
occasioned by the loss of some of her teeth, the pressure of its sharp
point against the roof of her mouth, and the smoke setting her
coughing, forced her to relax her hold, when the man’s thumb was
got out of her grasp terribly lacerated. Immediately thereafter she
was tossed in the midst of the flames, and forcibly held there by
means of long prongs; and the fire soon reaching the vital parts, the
poor wretch’s screams and imprecations became so horrifying, that
one of the bystanders, unable to bear it any longer, threw a large
stone at her head, which, hitting her on the temples, deprived her of
sense and motion.
Their vengeance satisfied, the people immediately dispersed,
having first pledged themselves to the strictest secrecy. Most of them
returned home, but a few went back to Elie Anderson’s, whose house,
and everything belonging to her, had been set on fire by the furious
multitude. They then retired, leaving a few men to watch the remains
of the children, till coffins could be procured for them. “Never in a’
my days,” said John Maxwell, when speaking of it afterwards, “did I
weary for daylight as I did that night. When the smoke smothered
the fire, and it was quite dark, we didna mind sae muckle; but when a
rafter or a bit o’ the roof fell in, and a bleeze raise, then the firelight
shining on the ghastly faces of the puir wee innocents a’ laid in a row,
—it was mair than we could weel stand; and it was mony a day or I
was my ainsel again.”
 Chapter III.
Next morning the parents met, and it being agreed that all their
little ones should be interred in one grave, and that the funeral
should take place on the following day, the necessary preparations
were accordingly made. In the meantime, Matty went over to her
brother John Maxwell, to tell him, if possible, to persuade David
Williams not to attend the funeral, as she was sure he could not
stand it. “He hadna closed his ee,” she said, “since that terrible night,
and had neither ate nor drank, but had just wandered up and down
between the house and the fields, moaning as if his heart would
break.” John Maxwell promised to speak to David, but when he did
so, he found him so determined on attending, that it was needless to
say any more on the subject.
On the morning of the funeral, David Williams appeared very
composed; and John Maxwell was saying to some of the neighbours
that he thought he would be quite able to attend, when word was
brought that Geordie Turnbull had died that morning of lock-jaw,
brought on, it was supposed, as much from the idea of his having
been bitten by a witch, or one that was not canny, as from the injury
done to him.
This news made an evident impression on David Williams, and he
became so restless and uneasy, and felt himself so unwell, that he at
one time declared he would not go to the funeral; but getting
afterwards somewhat more composed, he joined the melancholy
procession, and conducted himself with firmness and propriety from
the time of their setting out till all the coffins were lowered into the
grave. But the first spadeful of earth was scarcely thrown in, when
the people were startled by his breaking into a long and loud laugh;—
“There she’s!—there she’s!” he exclaimed; and, darting through the
astonished multitude, he made with all his speed to the gate of the
churchyard.
“Oh! stop him,—will naebody stop him?” cried his distracted wife;
and immediately a number of his friends and acquaintances set off
after him, the remainder of the people crowding to the churchyard
wall, whence there was an extensive view over the surrounding
country. But quickly as those ran who followed him, David Williams
kept far a-head of them, terror lending him wings,—till at length, on
slackening his pace, William Russel, who was the only one near,
gained on him, and endeavoured, by calling in a kind and soothing
manner, to prevail on him to return. This only made him increase his
speed, and William would have been thrown behind farther than
ever, had he not taken a short cut, which brought him very near him.
“Thank God, he will get him now!” cried the people in the
churchyard; when David Williams, turning suddenly to the right,
made with the utmost speed towards a rising ground, at the end of
which was a freestone quarry of great depth. At this sight a cry of
horror arose from the crowd, and most fervently did they pray that
he might yet be overtaken; and great was their joy when they saw
that, by the most wonderful exertion, William Russel had got up so
near as to stretch out his arm to catch him; but at that instant his
foot slipped, and ere he could recover himself, the unhappy man,
who had now gained the summit, loudly shouting, sprung into the
air.
“God preserve us!” cried the people, covering their eyes that they
might not see a fellow-creature dashed in pieces; “it is all over!”
“Then help me to lift his poor wife,” said Isabel Lawson. “And now
stan’ back, and gie her a’ the air, that she may draw her breath.”
“She’s drawn her last breath already, I’m doubting,” said Janet
Ogilvie, an old skilful woman; and her fears were found to be too
true.
“An’ what will become o’ the poor orphans?” said Isabel.
She had scarcely spoken, when Sir George Beaumont advanced,
and, taking one of the children in each hand, he motioned the people
to return towards the grave.
“The puir bairns are provided for now,” whispered one to another,
as they followed to witness the completion of the mournful
ceremony. It was hastily finished in silence, and Sir George having
said a few words to his steward, and committed the orphans to his
care, set out on his way to the Hermitage, the assembled multitude
all standing uncovered as he passed, to mark their respect for his
goodness and humanity.
 As might have been expected, the late unhappy occurrences greatly
affected Lady Beaumont’s health, and Sir George determined to quit
the Hermitage for a time; and directions were accordingly given to
prepare for their immediate removal. While this was doing, the
friend who had been with Elie Anderson in the prison happened to
call at the Hermitage, and the servants crowded about her, eager to
learn what had induced Elie to commit such crimes. When she had
repeated what Elie had said, a young woman, one of the servants,
exclaimed, “I know who’s been the cause of this; for if Bet,”——and
she suddenly checked herself.
“That must mean Betsy Pringle,” said Robert, who was her
sweetheart, and indeed engaged to her; “so you will please let us hear
what you have to say against her, or own that you’re a slanderer.”
“I have no wish to make mischief,” said the servant; “and as what I
said came out without much thought, I would rather say no more;
but I’ll not be called a slanderer neither.”
“Then say what you have to say,” cried Robert; “it’s the only way to
settle the matter.”
“Well, then,” said she, “since I must do it, I shall. Soon after I came
here, I was one day walking with the bairns and Betsy Pringle, when
we met a woman rather oddly dressed, and who had something
queer in her manner, and, when she had left us, I asked Betsy who it
was. ‘Why,’ said Betsy, ‘I don’t know a great deal about her, as she
comes from another part of the country; but if what a friend of mine
told me lately is true, this Elie Anderson, as they call her, should
have been hanged.’
“‘Hanged!’ cried Miss Charlotte; ‘and why should she be hanged,
Betsy?’
“‘Never you mind, Miss Charlotte,’ said Betsy, ‘I’m speaking to
Fanny here.’
“‘You can tell me some other time,’ said I.
“‘Nonsense,’ cried Betsy, ‘what can a bairn know about it? Weel,’
continued she, ‘it was believed that she had made away with John
Anderson, her gudeman.’
“‘What’s a gudeman, Betsy?’ asked Miss Charlotte.
“‘A husband,’ answered she.
 “‘And what’s making away with him, Betsy?’
“‘What need you care?’ said Betsy.
“‘You may just as well tell me,’ said Miss Charlotte; ‘or I’ll ask Elie
Anderson herself all about it, the first time I meet her.’
“‘That would be a good joke,’ said Betsy, laughing; ‘how Elie
Anderson would look to hear a bairn like you speaking about a
gudeman, and making away with him; however,’ she continued, ‘that
means killing him.’
“‘Killing him!’ exclaimed Miss Charlotte. ‘Oh, the wretch; and how
did she kill him, Betsy?’
“‘You must ask no more questions, miss,’ said Betsy, and the
subject dropped.
“‘Betsy,’ said I to her afterwards, you should not have mentioned
these things before the children; do you forget how noticing they
are?’
“‘Oh, so they are,’ said Betsy, ‘but only for the moment; and I’ll
wager Miss Charlotte has forgotten it all already.’
“But, poor thing,” Fanny added, “she remembered it but too well.”
“I’ll not believe this,” cried Robert.
“Let Betsy be called, then,” said the housekeeper, “and we’ll soon
get at the truth.” Betsy came, was questioned by the housekeeper,
and acknowledged the fact.
“Then,” said Robert, “you have murdered my master’s daughter,
and you and I can never be more to one another than we are at this
moment;” and he hastily left the room.
Betsy gazed after him for an instant, and then fell on the floor. She
was immediately raised up and conveyed to bed, but recovering soon
after, and expressing a wish to sleep, her attendant left her. The
unhappy woman, feeling herself unable to face her mistress after
what had happened, immediately got up, and, jumping from the
window, fled from the Hermitage. The first accounts they had of her
were contained in a letter from herself to Lady Beaumont, written on
her death-bed, wherein she described the miserable life she had led
since quitting the Hermitage, and entreating her ladyship’s
forgiveness for the unhappiness which she had occasioned.
 “Let what has happened,” said Lady Beaumont, “be a warning to
those who have the charge of them, to beware of what they say
before children;—a sentiment which Sir George considered as so just
and important, that he had it engraven on the stone which covered
the little innocents, that their fate and its cause might be had in
everlasting remembrance.”—“The Odd Volume.”
 AN ORKNEY WEDDING.

By John Malcolm.
To me more dear, congenial to my heart,
One native charm, than all the gloss of art.—Goldsmith.

Gentle reader! you, I doubt not, have seen many strange sights,
and have passed through a variety of eventful scenes. Perhaps you
have visited the Thames Tunnel, and there threaded your way under
ground and under water, or you may have witnessed Mr Green’s
balloon ascent, and seen him take an airing on horseback among the
clouds.
Perhaps, too, you have been an observer of human life in all its
varieties and extremes: one night figuring away at Almack’s with
aristocratic beauty, and the next footing it with a band of gipsies in
Epping Forest. But, pray tell me, have you ever seen an Orkney
Wedding? If not, as I have just received an invitation to one,
inclusive of a friend, you shall, if it so please you, accompany me to
that scene of rural hospitality.
In conformity with the custom of the country, I have sent off to the
young couple a pair of fowls and a leg of mutton, to play their parts
upon the festive board; and as every family contributes in like
manner, a general pic-nic is formed, which considerably diminishes
the expense incident to the occasion; although, as the festivities are
frequently kept up for three or four days by a numerous assemblage
of rural beauty and fashion, the young people must contrive to live
upon love, if they can, during the first year of their union, having
little else left upon which to subsist, except the fragments of the
mighty feast.
 Well, then, away we go, and about noon approach the scene of
festivity,—a country-seat built in the cottage style, thatched with
straw, and flanked with a barn and a well-filled corn-yard, enclosed
with a turf-dyke.
The wedding company are now seen making their way towards the
place of rendezvous; and the young women, arrayed in white robes of
emblematic purity, exhibit a most edifying example of economy.
With their upper garments carried to a height to which the fashion of
short petticoats never reached even at Paris, they trip it away
barefooted through the mud, until they reach the banks of a purling
stream, about a quarter of a mile distant from the wedding-house.
Here their feet, having been previously kissed by the crystal waters,
and covered with cotton stockings, which in whiteness would fain vie
with the skin they enviously conceal, are inserted into shoes, in
whose mirror of glossy black the enamoured youth obtains a peep of
his own charms, while stooping down to adjust their ties into a love-
knot.
Immediately in front of the outer-door, or principal entrance of the
house, and answering the double purpose of shelter and ornament,
stands a broad square pile, composed of the most varied materials,
needless to be enumerated, and vulgarly denominated a midden,
around the base of which some half-dozen of pigs are acting the part
of miners, in search of its hidden treasures. It is separated from the
house by a sheet of water, tinged with the fairest hues of heaven and
earth, viz., blue and green, and over which we pass by a bridge of
stepping-stones.
And now, my friend, before entering the house, it may be as well to
consider what character you are to personate during the
entertainment; for the good people in these islands, like their
neighbours of the mainland of Scotland, take that friendly interest in
other people’s affairs, which the thankless world very unkindly
denominates impertinent curiosity.
If I pass you off as a lawyer, you will immediately be overwhelmed
with statements of their quarrels and grievances; for they are main
fond of law, and will expend the hard-earned savings of years in
litigation, although the subject-matter of dispute should happen to
be only a goose. You must not, therefore, belong to the bar, since, in
the present case, consultations would produce no fees.
 I think I shall therefore confer upon you the degree of M.D., which
will do as well for the occasion as if you had obtained it by purchase
at the University of Aberdeen; although I am not sure that it also
may not subject you to some trouble in the way of medical advice.
And now having safely passed over the puddle, and tapped gently
at the door, our arrival is immediately announced by a grand musical
chorus, produced by the barking of curs, the cackling of geese, the
quacking of ducks, and the grunting and squeaking of pigs. After this
preliminary salutation, we are received by the bridegroom, and
ushered, with many kind welcomes, into the principal hall, through a
half open door, at one end of which we are refreshed with a picture of
rural felicity, namely, some sleek-looking cows, ruminating in
philosophical tranquillity on the subject of diet.
In the middle of the hall is a large blazing turf fire, the smoke of
which escapes in part through an aperture in the roof, while the
remainder expands in the manner of a pavilion over the heads of the
guests.
A door at the other end of the hall opens into the withdrawing-
room, the principal furniture of which consists of two large chests
filled with oat and barley meal and home-made cheeses, a concealed
bed, and a chest of drawers. Both rooms have floors inlaid with
earth, and roofs of a dark soot colour, from which drops of a
corresponding hue occasionally fall upon the bridal robes of the
ladies, with all the fine effect arising from contrast, and ornamental
on the principle of the patch upon the cheek of beauty.
Separated from the dwelling-house only by a puddle dotted with
stepping-stones stands the barn, which, from its length and breadth,
is admirably adapted for the purposes of a ball-room.
Upon entering the withdrawing-room, which the good people with
admirable modesty call the ben, we take our seats among the elders
and chiefs of the people, and drink to the health of the young couple
in a glass of delicious Hollands, which, unlike Macbeth’s “Amen,”
does not stick in our throats, although we are well aware that it never
paid duty, but was slily smuggled over sea in a Dutch lugger, and
safely stowed, during some dark night, in the caves of the more
remote islands.
 The clergyman having now arrived, the company assembled, and
the ceremony of marriage being about to take place, the parties to be
united walk in, accompanied by the best man and the bride’s maid,—
those important functionaries, whose business it is to pull off the
gloves from the right hands of their constituents, as soon as the order
is given to “join hands,”—but this they find to be no easy matter, for
at that eventful part of the ceremony their efforts are long baffled,
owing to the tightness of the gloves. While they are tugging away to
no purpose, the bridegroom looks chagrined, and the bride is
covered with blushes; and when at last the operation is
accomplished, and perseverance crowned with success, the confusion
of the scene seems to have infected the parson, who thus blunders
through the ceremony:
“Bridegroom,” quoth he, “do you take the woman whom you now
hold by the hand, to be your lawful married husband?”
To which interrogation the bridegroom having nodded in the
affirmative, the parson perceives his mistake, and calls out, “Wife, I
mean.” “Wife, I mean,” echoes the bridegroom; and the whole
company are in a titter.
But, thank heaven, the affair is got over at last; and the bride being
well saluted, a large rich cake is broken over her head, the fragments
of which are the subject of a scramble among the bystanders, by
whom they are picked up as precious relics, having power to produce
love-dreams.
And now the married pair, followed by the whole company, set off
to church, to be kirked, as the phrase is. A performer on the violin
(not quite a Rossini) heads the procession, and plays a variety of
appropriate airs, until he reaches the church-door. As soon as the
party have entered and taken their seats, the parish-clerk, in a truly
impressive and orthodox tone of voice, reads a certain portion of
Scripture, wherein wives are enjoined to be obedient to their
husbands. The service is concluded with a psalm, and the whole
party march back, headed as before by the musician.
Upon returning from church, the company partake of a cold
collation, called the hansel, which is distributed to each and all by
the bride’s mother, who for the time obtains the elegant designation
of hansel-wife. The refreshments consist of cheese, old and new, cut
down in large slices, or rather junks, and placed upon oat and barley
cakes,—some of the former being about an inch thick, and called
snoddies.
These delicate viands are washed down with copious libations of
new ale, which is handed about in a large wooden vessel, having
three handles, and ycleped a three-lugged cog.[18] The etherial
beverage is seasoned with pepper, ginger, and nutmeg, and
thickened with eggs and pieces of toasted biscuit.
18. Also called the Bride’s cog.—Ed.
These preliminaries being concluded, the company return to the
barn, where the music strikes up, and the dancing commences with
what is called the Bride’s Reel; after which, two or three young men
take possession of the floor, which they do not resign until they have
danced with every woman present; they then give place to others,
who pass through the same ordeal, and so on. The dance then
becomes more varied and general. Old men and young ones, maids,
matrons, and grandmothers, mingle in its mazes. And, oh! what
movements are there,—what freaks of the “fantastic toe,”—what
goodly figures and glorious gambols in a dance;—compared to which
the waltz is but the shadow of joy, and the quadrille the feeble effort
of Mirth upon her last legs.
Casting an eye, however, upon the various performers, I cannot
but observe that the old people seem to have monopolised all the airs
and graces; for, while the young maidens slide through the reel in the
most quiet and unostentatious way, and then keep bobbing opposite
to their partners in all the monotony of the back-step, their more
gifted grandmothers figure away in quite another style. With a length
of waist which our modern belles do not wish to possess, and an
underfigure, which they cannot if they would, even with the aid of
pads, but which is nevertheless the true court-shape, rendering the
hoop unnecessary, and which is moreover increased by the swinging
appendages of huge scarlet pockets, stuffed with bread and cheese,
behold them sideling up to their partners in a kind of echellon
movement, spreading out their petticoats like sails, and then, as if
seized with a sudden fit of bashfulness, making a hasty retreat
rearwards. Back they go at a round trot; and seldom do they stop
until their career of retiring modesty ends in a somersault over the
sitters along the sides of the room.
 The old men, in like manner, possess similar advantages over the
young ones; the latter being sadly inferior to their seniors in address
and attitudes. Nor is this much to be wondered at, the young
gentlemen having passed most of their summer vacations at Davis’
Straits, where their society consisted chiefly of bears; whereas the old
ones are men of the world, having in early life entered the Company’s
service (I do not mean that of the East Indies, but of Hudson’s Bay),
where their manners must no doubt have been highly polished by
their intercourse with the Squaws, and all the beauty and fashion of
that interesting country.
Such of them as have sojourned there are called north-westers,
and are distinguished by that modest assurance, and perfect ease and
self-possession, only to be acquired by mixing frequently and freely
with the best society. Indeed, one would suppose that their manners
were formed upon the model of the old French school; and queues
are in general use among them—not, however, those of the small
pigtail kind, but ones which in shape and size strongly resemble the
Boulogne sausage.
And now, amidst these ancients, I recognise my old and very
worthy friend, Mr James Houston, kirk-officer and sexton of the
parish, of whom a few words, perhaps, may not be unacceptable.
His degree of longitude may be about five feet from the earth, and
in latitude he may extend at an average to about three. His
countenance, which is swarthy, and fully as broad as it is long,
although not altogether the model which an Italian painter would
select for his Apollo, would yet be considered handsome among the
Esquimaux; or, as James calls them, the Huskinese. His hair, which
(notwithstanding an age at which Time generally saves us the
expense of the powder-tax) is jet black, is of a length and strength
that would not shrink from comparison with that of a horse’s tail,
and hangs down over his broad shoulders in a fine and generous
flow. The coat which he wears upon this, as upon all other occasions,
is cut upon the model of the spencer; its colour, a “heavenly blue,”
varied by numerous dark spots, like clouds in a summer sky; while
his nether bulk is embraced by a pair of tight buckskin
“unmentionables.”
Extending from the bosom down to the knee he wears a leather
apron. This part of his dress is never dispensed with, except at
church; and though I have not been able to ascertain its precise
purpose with perfect certainty, I am inclined to think it is used as a
perpetual pinafore, to preserve his garments from the pollution of
soup and grease-drops at table.
The principal materials of his dress are, moreover, prepared for
use by his own hands: Mr Houston being at once sole proprietor and
operative of a small manufactory, consisting of a single loom; when
not employed at which, or in spreading the couch of rest in the
churchyard, he enjoys a kind of perpetual otium cum dignitate.
His chief moveables, in addition to the loom, consist of three
Shetland ponies and a small Orkney plough, by the united aid of
which he is enabled to scratch up the surface of a small estate, which
supplies him with grain sufficient for home consumption, but not for
exportation.
His peculiar and more shining accomplishments consist in the art
of mimicking the dance of every man and woman in the parish,
which he does with a curious felicity, and in executing short pieces of
music on that sweetest of lyres, the Jew’s harp.
Like most of his profession, he is a humorist; and though he has
long “walked hand-in-hand with death,” nobody enjoys life with a
keener relish at the festive board or the midnight ball, which he finds
delightful relaxations from his grave occupations during the day;
and yet even these latter afford him a rare and consolatory joy denied
to other men,—I mean that of meeting with his old friends, after they
have been long dead, and of welcoming, with a grin of recognition,
the skulls of his early associates, as he playfully pats them with his
spade, and tosses them into the light of day.
But it is in his capacity of kirk-officer that Mr Houston appears to
the greatest advantage, while ushering the clergyman to the pulpit,
and marching before him with an air truly magnificent, and an
erectness of carriage somewhat beyond the perpendicular, he
performs his important function of opening and shutting the door of
the pulpit, and takes his seat under an almost overwhelming sense of
dignity, being for the time a kind of lord high constable, with whom
is entrusted the execution of the law. And that he does not bear the
sword in vain is known to their cost, by all the litigious and
churchgoing dogs of the parish; for no sooner do they begin to growl
and tear each other, with loud yells, which they generally do, so as to