Table Of ContentMEDICAL RADIOLOGY
Diagnostic Imaging and Radiation Oncology
Editorial Board
Founding Editors 1.W . Brady, M. W. Donner(t),
H.-P. Heilmann, EH.W. Heuck
Current Editors
Diagnostic Imaging A.1. Baert, Leuven
E H. W. Heuck, Stuttgart
J.E. Youker, Milwaukee
Radiation Oncology 1.W . Brady, Philadelphia
H.-P. Heilmann, Hamburg
Springer
Berlin
Heidelberg
New York
Barcelona
Hong Kong
London
Milan
Paris
Singapore
Tokyo
H. S. Thomsen· R. N. Muller· R. F. Mattrey (Eds.)
Trends in
Contrast Media
With Contributions by
R. Agati . T. Albrecht· T. Almen . I. Berry· M. D. Blaufox . M. J. K. Blomley
H. Bosmans . A. A. Brayman· W. H. Bush, Jr. . C. Catalano· P. P. Chang· C. Church
M. Clanet . R. H. Cohan· B. Coley· B. Cotter· D. O. Coscrove . B. Cotter· A. N. DeMaria
J.F. Desreux . R. J. Eckersley· J. H. Ellis· A. K. Fahlvik . S. L. Fossheim . B. Frennby
D. Gilsoul· M.S. Girard· K. Golman· A. Greco· R.W. Katzberg· A. Kornerup Hansen
E. P. Krenning· G.-P. Krestin· D. J. Kwekkeboom· A. L'Abbate· A. Laghi· P. Leander
M. Leonardi· M. Lombardi· G. Manelfe . G. Marchal· R. F. Mattrey . M. T. McNamara
J. K. Moran· A. Nrevestad . H.-Y. Oei . R. A. Older· P. Pavone· T. Pelura . H. M. Pollack
J. P. Ranjeva . P. A. Rinck· K.K. Shung . C. B. Sirlin . F. Stacul· G. C. Steinbach
G. Sterner· I. M. Stilbo· O. Svendsen· H. S. Thomsen· G. Torheim· R. Towart
E. C. Unger· H. J. Weinmann· E. R. Wisner· G. L. Wolf
Foreword by
A. 1. Baert
With 224 Figures in 409 Separate Illustrations, 22 in Color
Springer
HENRIK S. THOMSEN, MD
Department of Diagnostic Radiology 54E2
Copenhagen University Hospital at Herlev
Herlev Ringvei 75
DK-2730 Herlev
Denmark
ROBERT N. MULLER, MD
ProfesSor, Faculte de Medecine
Departement de Chimie Organique
& Laboratoire RMN
Universite de Mons-Hainaut
24, Aveneu du Champ de Mars
B-7000 Mons
Belgium
ROBERT F. MATTREY, MD
UCSD Medical Center
Department of Radiology
200 W. Arbor Drive
San Diego, CA 92109-8756
USA
MEDICAL RADIOLOGY· Diagnostic Imaging and Radiation Oncology
Continuation of
Handbuch der medizinischen Radiologie
Encyclopedia of Medical Radiology
ISBN-13:978-3-642-64136-7 e-ISBN-13:978-3-642-59814-2
DOl: 10.1007/978-3-642-59814-2
Library of Congress Cataloging-in-Publication Data. Trends in contrast media I H. S. Thomsen, R. N. Muller, R. F. Mattrey
(eds.) ; with contributions by T. Albrecht ... [etal.] ; foreword by A. 1. Baert. p. cm. --(Medical radiology) Includes
bibliographical references and index.ISBN-13:978-3-642-64136-7 (alk. paper) 1. Contrast media. I. Thomsen, Henrik S. II.
Muller, Robert N. III. Mattrey, Robert F. IV. Albrecht, T. (Thomas) V. Series [DNLM: 1. Contrast Media. WN 160T792
1998] RC78.7.C65T74 1998 616.07'54--dc21 DNLM/DLC for Library of Congress 98-28592 CIP
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Foreword
0\
The use contrast media within diagnostic radiology has been firmly established
for many years now. Radiologic contrast media render immense services in daily
clinical practice to innumerable patients all over the world. When the new cross
sectional modalities such as computed tomography and magnetic resonance ima
ging were introduced into clinical practice it rapidly became evident that the judi
cious use of contrast media allows the optimal exploitation of the great diagnostic
potential of these revolutionary methods. More recently, efforts to create specific
contrast media for ultrasound imaging have been successful, and the first benefi
cial results of their application in daily practice are now evident.
The aim of this book is to bring together the results of the tremendous research
that has been performed during recent years in order to develop specific contrast
media for magnetic resonance imaging and ultrasonography and also to develop
safer contrast media for the classical radiologic techniques as well as computed
tomography. Moreover, the book provides a comprehensive overview of the indica
tions for and applications of these new contrast media in clinical radiology. Finally,
risks, side-effects, and complications which may occur with the use of these drugs
are covered appropriately.
The three editors are leading and well-known experts in their specific field. They
have been very successful in ensuring the collaboration of so many intern~tionally
known specialists to cover the different topics dealt with in this book.
It is my pleasure to congratulate the editors and all the authors for their excellent
contributions. I am convinced that this volume includes the latest, up-to-date infor
mation that radiologists and other clinicians are looking for in order to alow them
to provide the best possible care to their patients and to maintain their standards
of excellent clinical practice.
I sincerely hope that this book will meet the expectations of all those interested
in updating their knowledge about radiologic contrast media and I wish this
volume the same success as the previous volumes published in our series "Medical
Radiology". I would appreciate every constructive criticism that might be offered.
Leuven ALBERT 1. BAERT
Preface
During the past two decades more has happened in diagnostic imaging than
during the first 8 decades following the birth of the specialty in 1895. A variety of
new modalities - computed tomography, magnetic resonance imaging, ultrasono
graphy, gamma camera imaging, and positron emission tomography - have been
introduced and all have shown their importance in the workup of patients with
symptoms/signs of disease. Initially it was claimed that neither magnetic resonan
ce imaging nor ultrasonography required the use of contrast media. Today we know
that this was incorrect. With all modalities, use of contrast media increases the
information acquired, and accordingly there has also been enormous development
with regard to contrast media during the past two decades. High-osmolar contrast
media have been available since the early 1950s, but their role has now almost com
pletely been taken over by the low- and iso-osmolar contrast media. Ultra
sonography has got its bubbles. Magnetic resonance imaging uses agents distribu
ted in the extracellular phase and organ-specific agents. Nuclear medicine has
access to several pharmaceuticals attached to an isotope. More contrast media are
on their way in order to improve imaging with the various modalities to the bene
fit of the patient. The technological development is now rapid, and sometimes it
bypasses the much slower pharmaceutical projects. Therefore it is difficult to pre
dict the future for the various old and new contrast media for diagnostic imaging.
Nevertheless, diagnostic imaging has moved from being a specialty using one class
of contrast media to a multipharmaceutical business. Radiologists now have many
drugs on their shelves: it has not become easier to be a radiologist!
During recent years I have gained the impression that there is a strong wish
among many radiologists to have an overview on the current state of the art regar
ding contrast media and some recommendations for daily work. Therefore this
project was undertaken, with strong encouragement from Professor Albert L. Baert
and Springer-Verlag. This book is devoted to the general radiologist, being desi
gned to serve as a reference in his/her daily practice and to provide an update of
current knowledge. The reader will find chapters ranging from the history of con
trast media to what is going on in the laboratory, together with recommendations
on doses, use, and treatment of adverse effects. The book covers iodinated contrast
media used for x-ray examinations, radiopharmaceuticals employed for nuclear
medicine, agents usable with magnetic resonance and echo-increasing agents for
ultrasonography. It is my sincere hope that general radiologists will find it useful.
There would not have been a single word in this book without the assistance of
my co-editors Prof. Mattrey and Prof. Muller as well as the authors of the chapters.
VIII
I sincerely thank them all for their excellent contributions. I am fully aware of the
fact, that the project has taken the authors away from their families, clinical work,
and the research laboratory, and that at some institutions it is not as rewarding to
write a book chapter as it is to write an original paper published in a peer-reviewed
journal. Nevertheless, the chapters were written, and I am sure that the readers will
appreciate the end result.
The staff at Springer-Verlag did a tremendous job bringing the book together.
Many thanks to them. Finally my wife and three boys often did not see me owing to
this project; they did not complain. The book is devoted to Pia, Jannick, Michael,
and Ulrik
Between Bangkok and Singapore on SK 973 HENRIK S. THOMSEN
Contents
I Iodinated Contrast Media ................................................ 1
1 History of Iodinated Contrast Media
H. M. POLLACK . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
2 Design of X-ray Contrast Agents
G. L. WOLF ............................................................ 21
3 Biological Variation, Reproducibility, and Predictability of Experimental
Research in Animals
O. SVENDSEN and A. KORNERUP HANSEN ................................... 31
4 Experimental Testing of Iodinated Contrast Media Before Human Testing
R. TOWART and K. GOLMAN .............................................. 43
5 Phase I, II, III, and IV Studies: Good Clinical Practice
I.M. STILBO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 57
6 Currently Available Iodinated Contrast Media
F. STACUL ............................................................. 63
7 Clinical Doses of Contrast Media
R.A. OLDER. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 75
8 Determination of Glomerular Filtration Rate with Contrast Media
T. ALMEN, B. FRENNBY, and G. STERNER .................................... 81
9 Neurotoxicity
M. LEONARDI and R. AGATI .............................................. 95
10 Nephrotoxicity
H. S. THOMSEN ......................................................... 103
11 Adverse Reactions to Iodinated Radiographic Contrast Media
R. H. COHAN and J. H. ELLIS .............................................. 117
12 Treatment of Adverse Reactions
W. H. BUSH, Jr. . ........................................................ 133
New Agents
13 Hepatic Agents
P. LEANDER ............................................................ 141
14 Lymphatic Agents
E. R. WISNER AND R.W. KATZBERG ......................................... 149
x Contents
II Magnetic Resonance Contrast Media ...................................... 159
Chemistry and Physics
15 Chemical Synthesis of Paramagnetic Complexes
J. E DESREUX and D. GILSOUL ............................................ 161
16 Preparation and Structure-Activity Relationships of Particulate Magnetic Agents
A. NlEVESTAD, S. L. FOSSHEIM, and A. K. FAHLVIK ............................ 17l
17 Magnetic Resonance Contrast Agents of Increased Specificity
H.-J. WEINMANN ................................. ~ ..................... 183
Selected Applications of Magnetic Resonance Imaging Contrast Agents
18 Central Nervous System
I. BERRY, J.-P. RANJEVA, M. CLANET, and C. MANELFE ......................... 195
19 Liver and Pancreas
P. PAVONE,A. LAGHI, and C. CATALANO ..................................... 219
20 Heart
M.LoMBARDI and A. l'A BBATE ............................................ 223
21 Kidneys and Adrenal Glands
G. P. KRESTIN .......................................................... 233
22 The Musculoskeletal System
P. A. RINCK, A. GRECO, and M. T. McNAMARA ............................... 253
23 Contrast-Enhanced Magnetic Resonance Angiography
G. MARCHAL and H. BOSMANS ............................................ 267
24 Dynamic Contrast-Enhanced Magnetic Resonance Imaging
and Image Processing
G. TORHEIM and P. A. RINCK .............................................. 285
III Ultrasound Contrast Media .............................................. 297
History
25 Ultrasound Contrast Media: Past, Present, and Future
R.E MATTREY .......................................................... 299
Physics
26 Interaction of Ultrasound and Contrast Agents
P. P. CHANG and K. K. SHUNG ............................................. 311
27 Contrast-Specific Instrumentation and Its Potential Applications
G. C. STEINBACH ........................................................ 321
28 Bubble Destruction
C.B. SIRLIN, T. PELURA, and R.E MATTREY .................................. 333
29 Potential for Quantification
M.J.K. BLOMLEY, R.J. ECKERSLEY, and D.O. COSGROVE ......................... 343
Contents XI
Applications
30 The Vascular Space
C. B. SIRLIN, B. COLEY, and R. F. MATTREY ................................... 355
31 Tumor Imaging with Ultrasound Contrast
T. ALBRECHT and R. F. MATTREY .......................................... 367
32 Tissue Perfusion and Enhancement on Gray-scale
R. F. MATTREY and M. S. GIRARD .......................................... 383
33 Cardiac Applications
B. COTTER and A. N. DEMARIA ............................................ 393
34 Targeting and Delivery of Drugs with Ultrasound Contrast Agents
E. C. UNGER ............................................................ 405
Bioeffects
35 Can the Presence of Contrast Media Promote Ultrasound Bioeffects?
C. C. CHURCH and A.A. BRAYMAN ......................................... 413
IV Radiopharmaceuticals (Nuclear Medicine) .................................. 423
36 Imaging Techniques and Existing Agents
H.-Y. OEI, D.J. KWEKKEBOOM, and E.P. KRENNING ............................ 425
37 New and Future Trends in Radiopharmaceuticals
M. D. BLAUFOX and J. K. MORAN ........................................... 457
Subject Index ............................................................. 469
List of Contributors ........................................................ 477
