Exposure Criteria for Medical Diagnostic Ultrasound: II. Criteria Based on All Known Mechanisms

589 Pages·2002·3.388 MB·English

by  National Council on Radiation Protection and Measurements

NCRP Report No. 140
Exposure Criteria for Medical
Diagnostic Ultrasound: II. Criteria
Based on all Known Mechanisms
Recommendations of the
NATIONAL COUNCIL ON RADIATION
PROTECTION AND MEASUREMENTS
Issued December 31, 2002
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LibraryofCongressCataloging-in-PublicationData
NationalCouncilonRadiationProtectionandMeasurements.ScientificCommittee
66onBiologicalEffectsofUltrasound.
ExposurecriteriaformedicaldiagnosticultrasoundII,Criteriabasedonall
knownmechanisms/NationalCouncilonRadiationProtectionand
Measurements.
p.;cm.—(NCRPreport;no.140)
‘‘PreparedbyScientificCommittee66’’—Pref.
‘‘December2002.’’
Includesbibliographicalreferencesandindex.
ISBN0-929600-73-8
1. Diagnosis,Ultrasonic—Safetymeasures.2.Ultrasonicsinmedicine—
Toxicology.I.Title.II.Series
[DNLM:1.Ultrasonography—adverseeffects. 2. EquipmentSafety—
standards. 3. Hyperthermia,Induced. 4. UltrasonicTherapy—adverse
effects. 5. Ultrasonics. 6. Ultrasonography—instrumentation.
WB208N277e2002]
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Preface
This Report is the third in a series that includes NCRP Report
No. 74, Biological Effects of Ultrasound: Mechanisms and Clinical
ImplicationsandNCRPReportNo.113,ExposureCriteriaforMedi-
cal Diagnostic Ultrasound: I. Criteria Based on Thermal Mecha-
nisms.ThesethreereportswerepreparedbyScientificCommittee66
under the chairmanship of Wesley L. Nyborg. Dr. Nyborg and the
Committeerespondedadmirablytoitsmandatetoaddressthetopic
‘‘Biological Effects of Ultrasound and Exposure Criteria.’’
Ashasbeenpointedoutintheearlierreports,theuseofdiagnostic
ultrasound inmedicine has anenviable record forsafety. However,
newapplications, newprocedures,and newkindsof equipmentare
continually being introduced, higher output levels have become
available for some applications, and the extent of usage continues
toincrease.Hence,itisimportantthatusersbeinformedaswellas
possible for judging conditions under which the benefit/risk ratio is
or is not favorable.
ItisthepurposeofthisReport,anditstwopredecessors,topresent
backgroundforascientificallybasedapproachtosafetyassessment
for diagnostic ultrasound. These three reports are intended to help
themedicalcommunitytakeadvantageofnewdevelopmentsinclini-
cal practice, while maintaining its safety record.
InpreparingthepresentReport,ScientificCommittee66benefitted
greatlyfromcommentsreceivedthroughtheNCRPprocessesofcriti-
cal and Council review. In addition, many helpful suggestions were
received from J.S. Abramowicz, G.R. Harris, T.A. Siddiqi, and M.E.
Stratmeyer, all of whom are members of the American Institute of
Ultrasound in Medicine, a Collaborating Organization of the NCRP.
TheNCRPisalsogratefulfortheassistancegiventoScientificCom-
mittee 66 by S.H.P. Bly, National Research Council of Canada, and
thedetailed and cogent commentsreceived from F. Duck, Chairman
of the European Committee for Medical Ultrasound Safety.
This publication was made possible, in part, by Grant Number
R24 CA74296-05 from the National Cancer Institute (NCI) and its
contentsarethesoleresponsibilityoftheNCRPanddonotnecessar-
ily represent the official views of the NCI, National Institutes of
Health.
iii
iv / PREFACE
ServingonScientificCommittee66duringthepreparationofthis
Report were:
Wesley L. Nyborg, Chairman
University of Vermont
Burlington, Vermont
Members
Paul L. Carson Morton W. Miller
University of Michigan Medical University of Rochester
Center Medical Center
Ann Arbor, Michigan Rochester, New York
Edwin L. Carstensen Horace E. Thompson
University of Rochester University of Colorado
Rochester, New York Denver, Colorado
Floyd Dunn Marvin C. Ziskin
University of Illinois Temple University School of
Urbana, Illinois Medicine
Philadelphia, Pennsylvania
Douglas L. Miller
University of Michigan Medical
Center
Ann Arbor, Michigan
Consultants
Robert E. Apfel* Lawrence A. Crum
Yale University University of Washington
New Haven, Connecticut Seattle, Washington
Charles C. Church
University of Mississippi
Oxford, Mississippi
NCRP Secretariat
Constantine J. Maletskos, Consultant (1999–2002)
Eric E. Kearsley, Staff Scientist (1998–1999)
James A. Spahn, Jr., Senior Staff Scientist (1993–1998)
Cindy L. O’Brien, Managing Editor
The Council wishes to express its appreciation to the Committee
members for the time and effort devoted to the preparation of this
Report.
Thomas S. Tenforde
President
*deceased
Contents
Preface ........................................................................................ iii
1. Executive Summary ........................................................... 1
2. Introduction ......................................................................... 5
3. Nonthermal Mechanisms for Bioeffects in the
Absence of Cavitation ........................................................ 16
3.1 Introduction ..................................................................... 16
3.2 Acoustic Radiation Force and Radiation Pressure ....... 16
3.2.1 Application to Measurements of Acoustic
Power ..................................................................... 16
3.2.2 Auditory Response to Pulsed Ultrasound ........... 17
3.2.2.1 Electrical Response in the Cat Auditory
System ...................................................... 17
3.2.2.2 Human Sensing of Modulated
Ultrasound Applied to the Middle
Ear ............................................................ 18
3.2.2.3 Possibility of Hearing Pulsed
Ultrasound by Bone Conduction ............ 20
3.2.2.4 Audible Sound Produced In Utero by
Ultrasound Scanning .............................. 21
3.2.2.5 Auditory Phenomena During
Insonation of the Basilar Artery ............ 21
3.2.3 Reversible Modification of Membrane Potential
by Ultrasound Bursts ........................................... 22
3.2.4 Tactile Perception of Pulsed Ultrasound ............ 23
3.2.5 Acoustic Radiation Force Applied to the Eye ..... 24
3.2.6 Effects of Acoustic Radiation Forces on the
Heart ...................................................................... 26
3.2.7 Acoustic Radiation Forces and Torques on
Small Particles ...................................................... 26
3.3 Acoustic Streaming and Microstreaming ...................... 31
3.3.1 Theory .................................................................... 31
3.3.2 Acoustic Streaming Produced by Diagnostic
Ultrasound ............................................................ 33
3.3.3 Heat Transport by Acoustic Streaming .............. 34
3.3.4 Cellular Inactivation by Heat and Shear ........... 34
v
vi / CONTENTS
3.3.5 Enhanced Agglutination and Aggregation by
Acoustic Streaming ............................................... 36
3.3.6 Contraction of Myocardial Cells .......................... 37
3.3.7 Theory: Small-Scale Acoustic Streaming
(Microstreaming) ................................................... 37
3.3.8 Experiments with Acoustic Microstreaming in
Cells and in Cell Suspensions.............................. 38
3.3.9 In Vivo Experiments with Acoustic
Microstreaming ..................................................... 40
3.4 Unidentified Nonthermal Mechanisms .......................... 42
3.4.1 Introduction ........................................................... 42
3.4.2 Modification of Electrical Potentials and
Currents ................................................................ 42
3.4.3 Effects on Cardiac Performance .......................... 44
3.4.4 Stimulation of Bone Repair.................................. 44
3.4.5 Fetal Hemorrhage Caused by Lithotripsy .......... 47
3.4.6 Effects of Lithotripsy Under Noncavitating
Conditions.............................................................. 48
3.5 Summary .......................................................................... 48
4. Noninertial Cavitation; Gas-Body Activation ............. 50
4.1 Noninertial Cavitation Involving Free Bodies .............. 50
4.1.1 Introduction ........................................................... 50
4.1.2 Radial Pulsation of a Spherical Gas Bubble ....... 52
4.1.3 The Damping Constant for a Spherical Bubble . 56
4.1.4 Bubble Stability, Diffusion and Rectified
Diffusion ................................................................ 60
4.1.5 Scattering, Harmonics and Bubble Detection .... 62
4.1.6 Surface Waves ....................................................... 64
4.2 Activation of Stabilized Gas Bodies ............................... 65
4.2.1 Gas-Body Structures and Stability...................... 66
4.2.2 Bubbles Stabilized in Viscoelastic Media ........... 68
4.2.3 Gas Trapped in Pits or Pores............................... 71
4.2.4 Gas-Filled Channels ............................................. 76
4.2.5 Gas Bodies in Mammals ...................................... 77
4.3 Contrast Agents for Diagnostic Ultrasound .................. 78
4.3.1 Engineering of Stabilized Gas Bodies ................. 78
4.3.2 Physics of Contrast-Agent Excitation ................. 81
4.3.3 Stability and Nucleation of Inertial
Cavitation ............................................................. 84
4.3.4 Exploitation for Medical Purposes ...................... 88
4.4 Physical Consequences of the Vibration of Bubbles or
of Stabilized Gas Bodies ................................................. 92
CONTENTS / vii
4.4.1 Acoustic Power Radiated and Heat Generated
by a Vibrating Bubble .......................................... 93
4.4.2 Acoustic Radiation Force on a Gas Bubble,
Bubble Motion, and Associated Hydrodynamic
Shear ...................................................................... 95
4.4.3 Acoustic Radiation Force on a Particle Near a
Free Bubble or Stabilized Gas Body ................... 99
4.4.4 Acoustic Microstreaming Near a Vibrating Free
Bubble .................................................................... 100
4.4.5 Acoustic Microstreaming Near a Stabilized Gas
Body ....................................................................... 104
4.5 Summary .......................................................................... 105
5. Nonlinear Bubble Response; Inertial Cavitation........ 107
5.1 Introduction ................................................................... 107
5.2 Cavitation Theory; General .......................................... 109
5.3 Theory: Stable Noninertial Cavitation with Spherical
Symmetry........................................................................ 113
5.4 Theory: Inertial Cavitation with Spherical
Symmetry ...................................................................... 116
5.5 Theory: Cavitation Produced by Very Short Pulses of
Ultrasound ..................................................................... 120
5.6 Indeterminate Motion and Chaos ................................ 125
5.7 Surface Disturbances and Jet Formation ................... 127
5.8 Experimental Studies of Repetitive Inertial
Cavitation ....................................................................... 129
5.9 Sonoluminescence ......................................................... 131
5.10 Sonochemistry ............................................................... 135
5.11 Acoustical Parameters as Predictors of Inertial
Cavitation ...................................................................... 138
5.12 Summary ........................................................................ 142
6. Bioeffects of Noninertial Cavitation Involving Free
and Stabilized Gas Bodies in Non-Mammalian
Systems .................................................................................. 146
6.1 Introduction ..................................................................... 146
6.2 Studies with Cell Suspensions ....................................... 147
6.2.1 Gas-Filled Micropores........................................... 147
6.2.2 Ultrasound Contrast Agents ................................ 150
6.3 Tissues with Internal Gas Bodies .................................. 159
6.3.1 Plants ..................................................................... 159
6.3.2 Insects .................................................................... 161
6.4 Biophysical Analysis of Effects....................................... 165
6.4.1 Shear-Stress Hypothesis ...................................... 165
6.4.2 Applications of the Shear-Stress Hypothesis ..... 167
6.4.3 Other Mechanisms ................................................ 169
6.5 Summary .......................................................................... 169
viii / CONTENTS
7. Bioeffects of Inertial Cavitation In Vitro ..................... 171
7.1 Introduction ..................................................................... 171
7.1.1 Advantages and Disadvantages of Studies
Using Cells In Vitro .............................................. 171
7.1.2 Exposure Systems ................................................. 173
7.1.3 Biological Effects ................................................... 176
7.1.4 Mechanisms of Action of Ultrasound In Vitro .... 177
7.2 Cell Lysis ......................................................................... 179
7.2.1 Influence of Various Aspects of Exposure
Conditions.............................................................. 179
7.2.1.1 Exposure Parameters .............................. 179
7.2.1.2 Rotation of Exposure Tube and
Attenuation of Ultrasound by Bubbles .. 180
7.2.1.3 Mechanical Stirring ................................. 183
7.2.1.4 Standing Waves ....................................... 183
7.2.1.5 Bubble Recycling...................................... 184
7.2.1.6 Alternating the Ultrasound Propagation
Direction ................................................... 186
7.2.2 Mechanisms of Lysis ............................................ 187
7.2.2.1 Near-Boundary Streaming ...................... 187
7.2.2.2 Shear Near Moving Bubbles and Cell-
Bubble Collisions ..................................... 188
7.2.2.3 Bubble Implosion and Jets...................... 189
7.2.2.4 Free Radicals and Other
Sonochemicals .......................................... 190
7.2.3 Influence of Various Aspects of Cells and
Media ..................................................................... 192
7.2.3.1 Nucleation ................................................ 192
7.2.3.2 Cell Concentration ................................... 196
7.2.3.3 Ultrasound Contrast Agents ................... 198
7.2.3.4 Viscosity of the Medium .......................... 199
7.2.3.5 Multicellularity ........................................ 200
7.2.3.6 Gas Content of the Medium .................... 200
7.2.3.7 Temperature............................................. 200
7.2.3.8 Superposed Ionizing Radiation or
Chemotherapeutic Agents ....................... 201
7.3 Effects on Viable Cells .................................................... 202
7.3.1 Structure and Function ........................................ 202
7.3.1.1 Cell Morphology ....................................... 202
7.3.1.2 Electrical Excitability and Phagocytic
Activity ..................................................... 202
7.3.1.3 Growth ...................................................... 204
7.3.2 Effects on Deoxyribonucleic Acid ......................... 204
7.3.3 Membrane Permeabilization ................................ 206
7.4 Bioeffects and Lithotriptors ............................................ 208
7.5 Summary .......................................................................... 211
CONTENTS / ix
8. Bioeffects of Acoustic Cavitation in Mammalian
Tissues ................................................................................... 213
8.1 General Evidence for the Occurrence of Cavitation in
Tissues.............................................................................. 213
8.1.1 Studies of Brain and Liver................................... 213
8.1.2 Muscle .................................................................... 215
8.1.3 Paraplegia ............................................................. 217
8.1.4 Intestine ................................................................ 218
8.1.5 Blood ...................................................................... 219
8.1.6 Urine ..................................................................... 220
8.1.7 Summary ............................................................... 220
8.2 Evidence of Cavitation In Vivo from Lithotripsy .......... 220
8.2.1 Kidney and Liver .................................................. 221
8.2.2 Embryos ................................................................. 222
8.2.3 Lung ....................................................................... 222
8.2.4 Intestine ................................................................ 223
8.2.5 Heart ...................................................................... 223
8.2.6 Blood ...................................................................... 224
8.2.7 Negative Lithotriptor Fields ................................ 224
8.2.8 Hemorrhage Near Fetal Bone.............................. 225
8.3 Cavitation Effects with Diagnostically Relevant
Acoustic Fields ................................................................. 226
8.3.1 Lung ....................................................................... 226
8.3.2 Intestine ................................................................ 230
8.3.3 Heart ...................................................................... 231
8.3.4 Blood ...................................................................... 231
8.3.5 Hemorrhage Near Fetal Bone.............................. 232
8.3.6 Synergysm ............................................................. 232
8.3.7 Summary ............................................................... 232
8.4 Related Reports of Biological Effects ............................. 233
8.4.1 Endothelial Damage to Blood Vessels ................. 233
8.4.2 Ultrasonic Enhancement of Thrombolysis and
Perfusion................................................................ 234
8.4.3 Contrast Agents .................................................... 235
8.4.4 Sonochemical Tumor Treatment ......................... 237
8.5 Summary .......................................................................... 238
9. Models for Exposure Estimation in Human Beings ... 240
9.1 Introduction ..................................................................... 240
9.2 General Diagnostic Considerations ................................ 247
9.2.1 Patient-Specific Adjustment of the
Homogeneous Attenuation Model ........................ 247
9.2.2 Nonlinear Propagation and Other Effects
Limiting the Accuracy of Tissue Models for
Exposure Estimates .............................................. 252