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Contents
Contributors viii
Preface xix
Dedication xxi
List of ultrasound contrast agents under development xxii
I Physical Principles of Ultrasound Contrast Agents
Basic Scattering from Contrast Bubbles
1 Composition of contrast microbubbles: basic
chemistry of encapsulated and surfactant-coated
bubbles 3
Margaret A Wheatley
2 Physics of contrast microbubbles 15
Flemming Forsberg and William Tao Shi
Nonlinear Scattering f tom Contrast Bubbles
3 Contrast-specific imaging methods 25
Nico de Jong, Ayache Bouakaz, Peter J A Frinking
and Folkert J Ten Cate
4 Harmonic imaging with contrast microbubbles 37
Yuko Kono and Robert T Mattrey
5 Subharmonic imaging with contrast microbubbles 47
William Tao Shi, Flemming Forsberg and Barry B
Goldberg
Destruction of Contrast Bubbles
6 Optical and acoustic detection of bubble destruction
59
James E Chomas, Paul A Dayton, John Allen and
Katherine W Ferrara
7 Accelerated intermittent harmonic imaging 67
Thomas R Porter and Feng Xie
8 Acoustic emission imaging 71
Christopher J Harvey, Martin J K Blomley and
David O Cosgrove
Quantitative Measurements with Contrast Bubbles
9 Contrast kinetics and Doppler intensitometry 81
Martin J K Blomley, Christopher J Harvey, Robert J
Eckersley and David O Cosgrove
10 Blood flow and perfusion measurements:
background and clinical utility 90
Kevin Wei
11 Pressure measurements using contrast microbubbles
105
William Tao Shi, Flemming Forsberg and Joel S
Raichlen
Bioeffects and Safety of Ultrasound Contrast
12 In vitro measurements of bioeffects 113
William Tao Shi, J Brian Fowlkes and Flemming
Forsberg
13 In vivo measurements of bioeffects 121
J Brian Fowlkes and Douglas L Miller
II Contrast Echocardiography
14 Optimization of contrast echocardiograms 131
Joel S Raichlen
Evaluation of the Cardiac Chambers
15 Evaluation of the heart at rest 143
Paul A Grayburn and Joel S Raichlen
16 Evaluation of the heart during exercise and
pharmacologic stress 155
Sandeep Nathan and Steven B Feinstein
17 Three-dimensional echocardiography 165
Olaf T von Raam
Assessment of Myocardial Perfusion
18 Myocardial contrast echocardiography in acute
myocardial infarction 175
Robert A Pelberg, Jonathan R Lindner and Sanjiv
Kaul
19 Ultrasound contrast agents to detect myocardial
perfusion during stress echocardiography 189
Thomas R Porter and Feng Xie
20 Myocardial contrast echocardiography during septal
ethanol ablation for obstructive hypertrophic
cardiomyopathy 197
Anna Woo, Leonard Schwartz, E Douglas Wigle,
John Ross and Harry Rakowski
21 Intraoperative echocardiography and myocardial
viability assessment 213
Solomon Aronson
22 Enhancement of Doppler echocardiography 227
Helene von Bibra
III Radiological Applications of Contrast
23 The utility of contrast in the extra-cranial carotid
ultrasound examination 239
Michelle L Robbin
24 Transcranial color-coded duplex sonography (TCCS)
253
Ulrich Bogdahn, Thilo Holscher and Felix
Schlachetzki
25 Imaging of peripheral vascular pathology 267
Laurence Needleman and Daniel A Merton
26 Radiological applications of contrast agents in the
hepatobiliary system 277
Edward Leen
27 Ultrasound contrast agents in the evaluation of the
renal arteries 289
Edward G Grant and Michelle L Melany
28 Applications in the alimentary tract 297
Jill E Langer and Anna S Lev-Toaff
29 Applications in the genitourinary tract 311
Jeanne A Cullinan
30 Breast and prostate 327
Frank-Guenther Fuechsel and David O Cosgrove
IV Therapeutic applications of ultrasound contrast
agents
31 Thrombus-specific contrast agents for imaging and
thrombolysis 337
Evan C Unger, Qiu Wu, Thomas P McCreery and
Terry Onichi Matsunaga
32 Targeted drug delivery using intravenous
microbubbles 347
Thomas R Porter and Feng Xie
33 Targeted ultrasound contrast agents: identification of
endothelial dysfunction 353
Flordeliza S Villanueva, William R Wagner and
Alexander L Klibanov
V Economics of ultrasound contrast agents
34 Health economics evaluations and ultrasound
contrast agents: a primer 369
Mary Lou Chatterton, Robert R Corrato and David B
Nash
35 Is contrast-enhanced echocardiography worth the
added cost? 377
Leslee J Shaw
36 Ultrasound contrast agents: a commercial perspective
387
Harvey G Klein
Index 407
Contributors
John Allen PhD
Assistant Research Engineer
Department of Biomedical Engineering
1113 Academic Surge Building
University of California
Davis CA 95616
USA
Solomon Aronson MD FACC FCCP
Professor
Director, Cardiothoracic Anesthesia
Department of Anesthesia and Critical Care
The University of Chicago Medical Center
5841 South Maryland Avenue, MC 4028
Chicago IL 60637
USA
Martin J K Blomley MA MRCP FRCR MD
Senior Lecturer
Department of Imaging
Imperial College School of Medicine
Hammersmith Hospital
Du Cane Road
London W12 0NN
UK
Ulrich Bogdahn MD
Professor of Neurology
Director and Chair
Department of Neurology
University of Regensberg
Universitatstrasse 84
93053 Regensberg
Germany
Ayache Bouakaz PhD
Department of Cardiology and Experimental
Echocardiography
Thoraxcenter
Erasmus University Rotterdam, and
The Interuniversity Cardiology Institute Netherlands (ICIN),
Utrecht
PO Box 1738
3000 DR Rotterdam
The Netherlands
Mary Lou Chatterton PharmD
Fellowship Director, Project Director
Office of Health Policy
Thomas Jefferson University Hospital
1015 Walnut Street STE 115
Philadelphia PA 19107
USA
James E Chomas
Postgraduate Researcher
Department of Biomedical Engineering
1113 Academic Surge Building
University of California
Davis CA 95616
USA
Robert R Corrato MD
Executive Health Resources
110 West Eagle Road, Suite A
Havertown PA 19083
USA
David O Cosgrove FRCR FRCP
Professor of Clinical Ultrasound
Department of Imaging
Hammersmith Hospital
Du Cane Road
London W12 0NN
UK
Jeanne A Cullinan MD
Associate Professor of Radiology
Director of Woman's Imaging
University of Rochester Medical Center
601 Elmwood Avenue, Box 648
Rochester NY 14642
USA
Paul A Dayton
Postgraduate Researcher
Department of Biomedical Engineering
1113 Academic Surge Building
University of California
Davis CA 95616
USA
Nico de Jong PhD
Department of Cardiology and Experimental
Echocardiography
Thoraxcenter
Erasmus University Rotterdam, and
The Interuniversity Cardiology Institute Netherlands (ICIN),
Utrecht
PO Box 1738
3000 DR Rotterdam
The Netherlands
Robert J Eckersley PhD
MRC Research Fellow
Department of Imaging (Ultrasound)
Imperial College School of Medicine
Hammersmith Hospital
Du Cane Road
London W12 OHS
UK
Steven B Feinstein MD FACC
Professor and Director of Echocardiography
Cardiology Department
Rush Presbyterian St Luke Medical Center
1653 W Congress Parkway
Chicago IL 60612
USA
Katherine W Ferrara PhD
Professor and Chair
Department of Biomedical Engineering
1113 Academic Surge Building
University of California
Davis CA 95616
USA
Flemming Forsberg PhD
Associate Professor of Radiology and
Head of Research
Jefferson Ultrasound Research and Education Institute
Department of Radiology
Thomas Jefferson University
Suite 763J Main Building
132 South 10th Street
Philadelphia PA 19107
USA
J Brian Fowlkes PhD
Senior Associate Research Scientist
Basic Radiological Sciences Division
Department of Radiology
University of Michigan Health Systems
Kresge III Research Building, 83315
200 Zina Pitcher Place
Ann Arbor MI 48109
USA
Peter JA Frinking PhD
Department of Cardiology and Experimental
Echocardiography
Thoraxcenter
Erasmus University Rotterdam
PO Box 1738
3000 DR Rotterdam
The Netherlands
Frank-Guenther Fuechsel MD
Special Registrar and Research Fellow
Department of Imaging
Hammersmith Hospital
Du Cane Road
London W12 0NN
UK
Barry B Goldberg MD
Professor of Radiology and Director
Jefferson Ultrasound Research and Education Institute and
Division of Ultrasound
Department of Radiology
Jefferson Medical College
Thomas Jefferson University
Suite 763J Main Building
132 South 10th Street
Philadelphia PA 19107
USA
Edward G Grant MD
Professor and Vice Chairman
Department of Radiological Sciences
University of California, Los Angeles School of Medicine
Chairman, Imaging Department
Greater Los Angeles Veterans Affairs Healthcare System
11301 Wilshire Boulevard
Los Angeles CA 90073
USA
Paul A Grayburn MD FACC
Director of Echocardiography
Department of Internal Medicine
University of Texas Southwestern Medical Center and VA
Medical Center
5323 Harry Hines Boulevard
Dallas TX 75235
USA
Christopher J Harvey BSc MRCP FRCP
Research Fellow
Department of Imaging
Imperial School of Medicine
Hammersmith Hospital
Du Cane Road
London W12 0NN
UK
Thilo Holscher MD
Resident
Department of Neurology
University of Regensberg
Universitatstrasse 84
93053 Regensberg
Germany
Sanjiv Kaul MD FACC
Frances M Ball Professor of Cardiology
Professor of Medicine & Biomedical Engineering
Director, Cardiovascular Imaging Center
Cardiovascular Division
University of Virginia School of Medicine
Cobb Hall
Hospital Drive
Charlottesville VA 22908
USA
Harvey G Klein PhD
President
Klein Biomedical Consultants Inc.
215 West 90th Street
New York NY 10024
USA
Alexander L Klibanov PhD
Cardiovascular Division, Box 158
University of Virginia School of Medicine
Cobb Hall
Hospital Drive
Charlottesville VA 22908
USA
Yuko Kono MD
Assistant Research Scientist
Department of Radiology
University of California
San Diego Medical Center
200 West Arbor Drive
San Diego CA 92103
USA
Jill E Langer MD
Associate Professor of Radiology
Department of Radiology
University of Pennsylvania Medical Center
3400 Spruce Street
Philadelphia PA 19104
USA
Edward Leen MD FRCR
Consultant Radiologist
Department of Diagnostic Radiology
Royal Infirmary Glasgow
Queen Elizabeth Building
16 Alexandra Parade
Glasgow G31 2ER
UK
Anna S Lev-Toaff MD
Professor of Radiology
Thomas Jefferson University Medical Center
Gibbon Building 3390
111 South 11th Street
Philadelphia PA 19017
USA
Jonathan R Lindner MD FACC
Assistant Professor of Medicine
Cardiovascular Imaging Center
Cardiovascular Division
University of Virginia School of Medicine
Cobb Hall
Hospital Drive
Charlottesville VA 22908
USA
Thomas P McCreery MS
Director, Drug Discovery
ImaRx Therapeutics Inc.
1635 East 18th Street
Tucson AZ 85719
USA
Terry O Matsunaga PharmD PhD
Senior Director, New Product Chemistry
ImaRx Therapeutics Inc.
1635 East 18th Street
Tucson AZ 85719
USA
Robert F Mattrey MD
Professor of Radiology
Department of Radiology
University of California
San Diego Medical Center
200 West Arbor Drive
San Diego CA 92103
USA
Michelle L Melany MD
Staff Physician
CedarsSinai Hospital
8700 Beverly Boulevard
Los Angeles CA 90048
USA
Daniel A Merton BS RDMS
Technical Coordinator of Research
Jefferson Ultrasound Research and Education Institute
Department of Radiology
Jefferson Medical College
Thomas Jefferson University
132 South 10th Street
Philadelphia PA 19107
USA
Douglas L Miller PhD
Senior Research Scientist
Basic Radiological Sciences Division
Department of Radiology
University of Michigan Health Systems
Kresge III Research Building, 83315
200 Zina Pitcher Place
Ann Arbor MI 48109
USA
David B Nash MD MBA
Dr Raymond C and Doris N Grandon Professor of Health
Policy
Associate Dean, Jefferson Medical College
Director, Office of Health Policy and Clinical Outcomes
1015 Walnut Street, Suite 115
Philadelphia PA 19107
USA
Sandeep Nathan MD
Cardiology Department
Rush Presbyterian St Luke Medical Center
1653 W Congress Parkway
Chicago IL 60612
USA
Laurence Needleman MD
Associate Professor of Radiology
Jefferson Ultrasound Research and Education Institute
Department of Radiology
Jefferson Medical College
Thomas Jefferson University
132 South 10th Street
Philadelphia PA 19107
USA
Robert A Pelberg MD
Fellow in Cardiovascular Imaging
Cardiovascular Imaging Center
Cardiovascular Division
University of Virginia School of Medicine
Cobb Hall
Hospital Drive
Charlottesville VA 22908
USA
Thomas R Porter MD FACC
Associate Professor
Section of Cardiology, Department of Internal Medicine
University of Nebraska Medical Center
981165 Nebraska Medical Center
Omaha NE 66198
USA
Joel S Raichlen MD FACC FACP
Clinical Professor of Medicine and Director of Noninvasive
Cardiology
Division of Cardiology
Department of Medicine
Jefferson Medical College
Thomas Jefferson University
Division of Cardiology
Suite 763N Main Building
132 South 10th Street
Philadelphia PA 19107
USA
Harry Rakowski MD FRCP FACC
Professor of Medicine
Division of Cardiology
University of Toronto
Toronto General Hospital
200 Elizabeth Street
EN12-212
Toronto
Ontario M5G 2C4
Canada
Michelle L Robbin MD
Associate Professor
Chief of Ultrasound
University of Alabama Hospital at Birmingham
619 19th Street, South, JTN350
Birmingham AL 35249
USA
John Ross MD FRCP
Professor of Medicine
Division of Cardiology
University of Toronto
Toronto General Hospital
200 Elizabeth Street
EN12-234
Toronto
Ontario M5G 2C4
Canada
Felix Schlachetzki MD
Resident
Department of Neurology
University of Regensberg
Universitatstrasse 84
93053 Regensberg
Germany
Leonard Schwartz MD FRCP FACC
Associate Professor of Medicine
Division of Cardiology
University of Toronto
Toronto General Hospital
200 Elizabeth Street
EN12-204 Toronto
Ontario M5G 2C4
Canada
Leslee J Shaw PhD
Associate Professor of Health Policy & Management
Director, Technology Evaluation Center
Emory University
Grace Crum Rollins School of Public Health
1518 Clifton Road, NE, Room 638
Atlanta GA 30322
USA
William Tao Shi PhD
Associate Professor of Research
Department of Radiology
Thomas Jefferson University
Suite 7966 Main Building
132 South 10th Street
Philadelphia PA 19107
USA
Folkert J Ten Cate MD
Department of Cardiology and Experimental
Echocardiography Thoraxcenter
Erasmus University Rotterdam
PO Box 1738
3000 DR Rotterdam
The Netherlands
Evan C Unger MD
Professor of Radiology
Arizona Health Sciences Center
University of Arizona, and
President & CEO
ImaRx Therapeutics Inc.
1635 East 18th Street
Tucson AZ 85719
USA
Flordeliza S Villanueva MD FACC
Associate Professor of Medicine
University of Pittsburgh
200 Lothrop Street
S568 Scaife Hall
Pittsburgh PA 15213
USA
Helene von Bibra MD
Professor
Department of Cardiology
Thoracic Clinics
Karolinska Hospital
S-17176 Stockholm
Sweden
Olaf T von Ramm PhD
Thomas Lord Professor of Engineering
Center for Emerging Cardiovascular Technologies
Department of Biomedical Engineering
Duke University
Durham NC 27708
USA
William R Wagner PhD
Associate Professor of Surgery, Chemical Engineering &
Bio-Engineering
University of Pittsburgh
300 Technology Drive #434
Pittsburgh PA 15219
USA
Kevin Wei BSc MD FRCP(C)
Assistant Professor
Cardiovascular Division, Box 158
University of Virginia School of Medicine
Cobb Hall
Hospital Drive
Charlottesville VA 22908
USA
Margaret A Wheatley PhD
Professor
Department of Chemical Engineering and
School of Biochemical Engineering, Science and Health
Systems
Drexel University
32nd and Chestnut Streets
Philadelphia PA 19104
USA
E Douglas Wigle MD FRCP FACC
Professor of Medicine
Division of Cardiology
University of Toronto
Toronto General Hospital
200 Elizabeth Street
EN12-217
Toronto Ontario M5G 2C4
Canada
Anna Woo MD FRCP
Assistant Professor of Medicine
Division of Cardiology
University of Toronto
Toronto General Hospital
200 Elizabeth Street
EN12-218
Toronto
Ontario M5G 2C4
Canada
Qiu Wu PhD MBA
InveStar Capital
3600 Pruneridge Avenue #300
Santa Clara CA 95051
USA
Feng Xie
Research Assistant Professor
Section of Cardiology, Department of Internal Medicine
University of Nebraska Medical Center
981165 Nebraska Medical Center
Omaha NE 68198
USA
