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Allerton Conference for Ultrasonics in Biophysics and Bioengineering: Cavitation
Ultrasound in Med. & Biol. Vol. 13, No. 10, pp. 687-689, 1987 0301-5629/87 $3.00 + .00 Printed in the U.S.A. (c) 1987 Pergamon Journals, Ltd. All rights reserved.
REPORTS
ALLERTON CONFERENCE AND BIOENGINEERING:
FOR ULTRASONICS CAVITATION
IN BIOPHYSICS
The annual Allerton Conferences sponsored by the Bioacoustics Research Laboratory of the University of Illinois provides a unique forum for the exploration of current developments in ultrasonic biophysics. The format and locale is essentially the same as that introduced by William J. Fry in the early 1950's but the subject matter has come to be more highly specialized in recent years. On May 26-29, 1987 the topic was ultrasonic cavitation. Approximately 50 specialists from the United States, Canada, England, West Germany, Japan and Australia participated. Crum and Fowlkes from the University of Mississippi, Oxford, Mississippi, have observed chemiluminescence with single cycle pulses of 1 MHz ultrasound at threshold levels of about 1.7 MPa. The threshold for this indication of transient cavitation decreases monotonically with increasing pulse length leveling out for millisecond pulses and c.w. at approximately 0.4 MPa. The light flashes have been observed to occur repetitively - - suggesting that a single bubble collapses violently many times without fragmenting. Although, when introduced by Flynn, the term transient cavitation was used to describe the intensity of bubble collapse without reference to the stability of the bubble, in some usage, it subsequently has come to connote single, isolated cavitation events. To emphasize the stability of the bubbles which he has observed, Crum suggests that this phenomenon be called repetitive transient cavitation. Flynn and Church, University of Rochester, Rochester, N. Y., have developed a detailed analysis of the behavior of bubbles during the early phases of their excitation by ultrasound. The data provide graphic illustrations of the development of transient cavitation, the decrease in resonance frequency of the bubble with pressure amplitude and the development of harmonics, subharmonics and ultraharmonics. Delius, Clinical Gross Hadern, Munich, West Germany presented clear evidence of extravasation of erythrocytes in kidneys which had received clinically relevant treatments with a lithotripter. Vessel walls appear to be ruptured. Tubules in the treated region of the kidney may become filled with red cells and their linings appear to be damaged. The mechanism for soft tissue damage as well as fragmentation of kidney stones appears to involve cavitation. Daniels of the Oxford Hyperbaric Group, Oxford, England, has evidence for the presence in tissues of bubbles and of their growth in acoustic fields as low as 100 mW/cm 2. Growth of the bubbles appears to be related to temporal average intensity in pulsed fields. Atchley, Naval Postgraduate School, Monterey, California, showed that nucleation is not model dependent. Hence, whether cavitation will occur under given acoustic conditions depends primarily upon whether the nuclei exist and upon their size. Using paramagnetic spin-trapping adducts to detect free radicals, Riesz, National Cancer Institute, Bethesda, Maryland, reported that 6 gs pulses at 100 W/cm 2 with a 2 per cent duty factor produced OH radicals at a level comparable to a millirad of cobalt radiation. Suslick, University of Illinois, Urbana, Illinois, in a rather involved study of sonochemical reactions, has been able to show that the temperatures in the gas bubble in one specific case was 5000°K and in the liquid shell immediately outside the bubble the temperature was ~2000°K. In sonochemistry, Henglein, Hahn-Meitner Institut, Berlin, West Germany, finds pulsed fields to be much less effective than c.w. Apparently, a finite time is required after initiation of the sound field to build up an effective bubble population before the actual chemistry can take place at a sienificant rate. Miller, University of Rochester, Rochester, N. Y., reported qualified confirmations of the reports of mutations in tissue culture cells exposed to c.w. fields of the order of I0 to 30 W/cm 2 and of sister chromatid exchanges in lymphocytes at 2500 W/cm 2. Kondo, National Cancer Institute, Bethesda, Maryland, showed that iodine release and cell lysis is greatly reduced when gases such as oxygen or argon in the medium are replaced by N20. Mortimer, National Research Council, Ottawa, Ontario, advocated the use of terphathalic acid as a dosimeter for OH radicals. His preparation is compatible with physiologically useful conditions and is stable for long periods after interaction with the radicals. Carstensen, University of Rochester, Rochester, New York, reported that shock Waves per se have little effect upon the behavior of bubbles, and further, that in an asymetric shock wave the amplitude of the fundamental frequency in the wave is a promising predictor of the occurrence of transient cavitation. Eventually, it would be desirable to know what effects occur in mammalian tissues as a result of cavitation. Frlzzell, University of Illinois, Urbana, Illinois, has identified a number of candidate phenomena from his own studies of paralysis in neonatal mice and from the literature which appear to be cavitation related. From these results, he has constructed an intensity-time threshold curve for cavitation-related effects in mammalian tissues. 687
688
Reports
Fry, Indianapolis, Indiana, noted that, in the course of producing patterned thermal brain lesions, he discovered that it was necessary to remain below about 300 W/cm 2 to avoid producing nonthermal tissue damage that was presumably caused by cavitation. Dyson, Guys Hospital Medical School, London, England, has substantial evidence that certain therapeutic effects of ultrasound depend upon cavitation. In vitro studies suggest that stable bubbles may affect the transport properties of membranes. Dinno, University of Mississippi, Oxford, Mississippi, presented new data indicating that ultrasound alters the transport properties of frog skin by a nonthermal mechanism. The Conference organizers were L. Frizzell, and W. O'Brien, University of Illinois, L. Crum, University of Mississippi, S. Daniels, Oxford University, and P. Riesz, National Cancer Institute. Moderators for the Conference included E. Carstensen, University of Rochester, Rochester, New York, P. Edmonds, SRI International, Menlo Park, California, A. Mortimer, National Research Council, Ottawa, Ontario, K. Suslick, University of Illinois, Urbana, Illinois, and G. ter Haar, Institute of Cancer Research, Sutton, Surrey, United Kingdom. For information about the topic and time of the next Allerton Conference, contact L. FrizzeU or W. O'Brien, Bioacousties Research Laboratory, University of Illinois. Edwin L. Carstensen University of Rochester Rochester, N.Y.
Report of the 9th meeting of the European Committee for Ultrasound Radiation Safety the Watchdog C o m m i t t e e . Helsinki. June. 1987, -
The European Helsinki, Finland. A number of discussed. The was c o n s i d e r e d , with the addition
Watchdog
Committee
met
during
EUROSON
"87
in June
in
current topics relevant to the safety of m e d i c a l ultrasound were statement on safety issued by the group in Strasbourg in 1987 and was c o n f i r m e d as the g r o u p ' s stance on the safety question of an a d d e n d u m .
CLINICAL SAFETY STATEMENT Radiation Safety. EFSUM8.
from
the
Ultrasound for d i a g n o s t i c p u r p o s e s in use for about 25 years. Numerous sophistication have been undertaken in Until the publication of this statement ultrasound at d i a g n o s t i c intensities as effect to the fetus or mother.
European
Committee
for
Ultrasound
obstetrics has been in extensive clinical investigations, of various d e g r e e s of an e n d e a v o u r to detect adverse effects. none of these studies have shown that used today has led to any d e l e t e r i o u s
In view of the c u r r e n t lack of well d e s i g n e d , e p i d e m i o l o g i c a l studies, it is n e c e s s a r y to laboratory studies in vitro and in vivo.
c o n t r o l l e d , long term p r o s p e c t i v e resort to e v i d e n c e culled from
Diverse effects of potential clinical s i g n i f i c a n c e have been r e p o r t e d from a variety of b i o l o g i c a l systems subjected to pulsed and continuous wave d i a g n o s t i c ultrasound. Those that have been chosen for further study have either not been confirmed or have given conflicting results. The c o m m i t t e e e n d o r s e s the clinical safety statement made by the AlUM ( O c t o b e r 1983), while e m p h a s i z i n g the need for further investigations into b i o - e f f e c t s from physical, b i o l o g i c a l and cllinical standpoints. Routine clinical s c a n n i n g of every woman during p r e g n a n c y is not c o n t r a - i n d i c a t e d by the e v i d e n c e currently available from b i o l o g i c a l investigations and its p e r f o r m a n b c e should be left to clnlcal j u d g e m e n t .
REPORTS
ALLERTON CONFERENCE AND BIOENGINEERING:
FOR ULTRASONICS CAVITATION
IN BIOPHYSICS
The annual Allerton Conferences sponsored by the Bioacoustics Research Laboratory of the University of Illinois provides a unique forum for the exploration of current developments in ultrasonic biophysics. The format and locale is essentially the same as that introduced by William J. Fry in the early 1950's but the subject matter has come to be more highly specialized in recent years. On May 26-29, 1987 the topic was ultrasonic cavitation. Approximately 50 specialists from the United States, Canada, England, West Germany, Japan and Australia participated. Crum and Fowlkes from the University of Mississippi, Oxford, Mississippi, have observed chemiluminescence with single cycle pulses of 1 MHz ultrasound at threshold levels of about 1.7 MPa. The threshold for this indication of transient cavitation decreases monotonically with increasing pulse length leveling out for millisecond pulses and c.w. at approximately 0.4 MPa. The light flashes have been observed to occur repetitively - - suggesting that a single bubble collapses violently many times without fragmenting. Although, when introduced by Flynn, the term transient cavitation was used to describe the intensity of bubble collapse without reference to the stability of the bubble, in some usage, it subsequently has come to connote single, isolated cavitation events. To emphasize the stability of the bubbles which he has observed, Crum suggests that this phenomenon be called repetitive transient cavitation. Flynn and Church, University of Rochester, Rochester, N. Y., have developed a detailed analysis of the behavior of bubbles during the early phases of their excitation by ultrasound. The data provide graphic illustrations of the development of transient cavitation, the decrease in resonance frequency of the bubble with pressure amplitude and the development of harmonics, subharmonics and ultraharmonics. Delius, Clinical Gross Hadern, Munich, West Germany presented clear evidence of extravasation of erythrocytes in kidneys which had received clinically relevant treatments with a lithotripter. Vessel walls appear to be ruptured. Tubules in the treated region of the kidney may become filled with red cells and their linings appear to be damaged. The mechanism for soft tissue damage as well as fragmentation of kidney stones appears to involve cavitation. Daniels of the Oxford Hyperbaric Group, Oxford, England, has evidence for the presence in tissues of bubbles and of their growth in acoustic fields as low as 100 mW/cm 2. Growth of the bubbles appears to be related to temporal average intensity in pulsed fields. Atchley, Naval Postgraduate School, Monterey, California, showed that nucleation is not model dependent. Hence, whether cavitation will occur under given acoustic conditions depends primarily upon whether the nuclei exist and upon their size. Using paramagnetic spin-trapping adducts to detect free radicals, Riesz, National Cancer Institute, Bethesda, Maryland, reported that 6 gs pulses at 100 W/cm 2 with a 2 per cent duty factor produced OH radicals at a level comparable to a millirad of cobalt radiation. Suslick, University of Illinois, Urbana, Illinois, in a rather involved study of sonochemical reactions, has been able to show that the temperatures in the gas bubble in one specific case was 5000°K and in the liquid shell immediately outside the bubble the temperature was ~2000°K. In sonochemistry, Henglein, Hahn-Meitner Institut, Berlin, West Germany, finds pulsed fields to be much less effective than c.w. Apparently, a finite time is required after initiation of the sound field to build up an effective bubble population before the actual chemistry can take place at a sienificant rate. Miller, University of Rochester, Rochester, N. Y., reported qualified confirmations of the reports of mutations in tissue culture cells exposed to c.w. fields of the order of I0 to 30 W/cm 2 and of sister chromatid exchanges in lymphocytes at 2500 W/cm 2. Kondo, National Cancer Institute, Bethesda, Maryland, showed that iodine release and cell lysis is greatly reduced when gases such as oxygen or argon in the medium are replaced by N20. Mortimer, National Research Council, Ottawa, Ontario, advocated the use of terphathalic acid as a dosimeter for OH radicals. His preparation is compatible with physiologically useful conditions and is stable for long periods after interaction with the radicals. Carstensen, University of Rochester, Rochester, New York, reported that shock Waves per se have little effect upon the behavior of bubbles, and further, that in an asymetric shock wave the amplitude of the fundamental frequency in the wave is a promising predictor of the occurrence of transient cavitation. Eventually, it would be desirable to know what effects occur in mammalian tissues as a result of cavitation. Frlzzell, University of Illinois, Urbana, Illinois, has identified a number of candidate phenomena from his own studies of paralysis in neonatal mice and from the literature which appear to be cavitation related. From these results, he has constructed an intensity-time threshold curve for cavitation-related effects in mammalian tissues. 687
688
Reports
Fry, Indianapolis, Indiana, noted that, in the course of producing patterned thermal brain lesions, he discovered that it was necessary to remain below about 300 W/cm 2 to avoid producing nonthermal tissue damage that was presumably caused by cavitation. Dyson, Guys Hospital Medical School, London, England, has substantial evidence that certain therapeutic effects of ultrasound depend upon cavitation. In vitro studies suggest that stable bubbles may affect the transport properties of membranes. Dinno, University of Mississippi, Oxford, Mississippi, presented new data indicating that ultrasound alters the transport properties of frog skin by a nonthermal mechanism. The Conference organizers were L. Frizzell, and W. O'Brien, University of Illinois, L. Crum, University of Mississippi, S. Daniels, Oxford University, and P. Riesz, National Cancer Institute. Moderators for the Conference included E. Carstensen, University of Rochester, Rochester, New York, P. Edmonds, SRI International, Menlo Park, California, A. Mortimer, National Research Council, Ottawa, Ontario, K. Suslick, University of Illinois, Urbana, Illinois, and G. ter Haar, Institute of Cancer Research, Sutton, Surrey, United Kingdom. For information about the topic and time of the next Allerton Conference, contact L. FrizzeU or W. O'Brien, Bioacousties Research Laboratory, University of Illinois. Edwin L. Carstensen University of Rochester Rochester, N.Y.
Report of the 9th meeting of the European Committee for Ultrasound Radiation Safety the Watchdog C o m m i t t e e . Helsinki. June. 1987, -
The European Helsinki, Finland. A number of discussed. The was c o n s i d e r e d , with the addition
Watchdog
Committee
met
during
EUROSON
"87
in June
in
current topics relevant to the safety of m e d i c a l ultrasound were statement on safety issued by the group in Strasbourg in 1987 and was c o n f i r m e d as the g r o u p ' s stance on the safety question of an a d d e n d u m .
CLINICAL SAFETY STATEMENT Radiation Safety. EFSUM8.
from
the
Ultrasound for d i a g n o s t i c p u r p o s e s in use for about 25 years. Numerous sophistication have been undertaken in Until the publication of this statement ultrasound at d i a g n o s t i c intensities as effect to the fetus or mother.
European
Committee
for
Ultrasound
obstetrics has been in extensive clinical investigations, of various d e g r e e s of an e n d e a v o u r to detect adverse effects. none of these studies have shown that used today has led to any d e l e t e r i o u s
In view of the c u r r e n t lack of well d e s i g n e d , e p i d e m i o l o g i c a l studies, it is n e c e s s a r y to laboratory studies in vitro and in vivo.
c o n t r o l l e d , long term p r o s p e c t i v e resort to e v i d e n c e culled from
Diverse effects of potential clinical s i g n i f i c a n c e have been r e p o r t e d from a variety of b i o l o g i c a l systems subjected to pulsed and continuous wave d i a g n o s t i c ultrasound. Those that have been chosen for further study have either not been confirmed or have given conflicting results. The c o m m i t t e e e n d o r s e s the clinical safety statement made by the AlUM ( O c t o b e r 1983), while e m p h a s i z i n g the need for further investigations into b i o - e f f e c t s from physical, b i o l o g i c a l and cllinical standpoints. Routine clinical s c a n n i n g of every woman during p r e g n a n c y is not c o n t r a - i n d i c a t e d by the e v i d e n c e currently available from b i o l o g i c a l investigations and its p e r f o r m a n b c e should be left to clnlcal j u d g e m e n t .