Safety consideration of medical ultrasound necessarily involves the nonthermal mechanism of cavitation. If bodies of gas are initially present in a biological medium, then the special type of ultrasonic cavitation called gas body activation (GBA) occurs and can be biological- ly effective at relatively low levels of exposure. At higher levels, GBA progresses into more violent cavitation phenomenon with associated free radical generation and sonochemical effects. In mammals, GBA is expected to be a subtle phenomenon with infrequent, but potentially significant consequences. The physics of gas body activation has been studied in research on plants, insects and gas-filled micropores in hydrophobic membranes. This research will be continued by assessing new types of gas bodies including gas vesicles in blue-green algae, ultrasonic contrast agents, and the natural cavitation-nucleating gas bodies which apparently exist in vitro and in vivo. Theoretical investigation of the relation between nonthermal mechanisms, such as acoustic streaming and free radicals, and the resulting potential for bioeffects will provide general insights with predictive utility beyond the specific conditions of the experiments. Use of in vitro model systems, such as the gas-filled micropore, will be continued to assess the damaging ability of micro- streaming shear stresses and of the sonochemical products of cavitation in cultured cells. Finally, biophysical studies will be initiated in mammalian model systems for the measurement of GBA bioeffects under medically-relevant conditions. These interdisciplinary studies are carefully integrated and focussed on the elucidation of the role of GBA and cavitation in the medical biophysics of ultrasound. Since the oc- currence, action and effects of cavitation in mammals remain virtually unknown, basic information on the potential for GBA bioeffects is urgent- ly needed for risk assessment efforts. Knowledge of the bioeffects of gas body activation will aid in hypothesis development for possible future mammalian and epidemiological studies, and will help to form a basis for dosimetry and exposure criteria in the clinical situation.
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