Lung damage assessment from exposure to pulsed-wave ultrasound in the rabbit, mouse, and pig.

The principal motivation of the study was to assess experimentally the question: "Is the MI (Mechanical Index) an equivalent or better indicator of nonthermal bioeffect risk than I(SPPA.3) (derated spatial peak, pulse average intensity)?" To evaluate this question, the experimental design consisted of a reproducible biological effect in order to provide a quantitative assessment of the effect. The specific biological effect used was lung damage and the species chosen was the rabbit. This work was initiated, in part, by a study in which lung hemorrhage was observed in 7-week old C3H mice for diagnostic-type, pulsed-wave ultrasound exposures, and, therefore, 6- to 7-week old C3H mice were used in this study as positive controls. Forty-seven adult New Zealand White male rabbits were exposed to a wide range of ultrasound amplitude conditions at center frequencies of 3 and 6 MHz with all temporal exposure variables held constant. A calibrated, commercial diagnostic ultrasound system was used as the ultrasound source with output levels exceeding, in some cases, permissible FDA levels. The MI was shown to be at least an equivalent, and in some cases, a better indicator of rabbit lung damage than either the I(SPPA.3) or p(r.3) (derated peak rarefactional pressure), thus answering the posed question positively. Further, in situ exposure conditions were estimated at the lung pleural surface (PS); the estimated in situ I(SPPA.PS) and p(r.PS) exposure conditions tracked lung damage no better than I(SPPA.3) and p(r.3), respectively, whereas the estimated in situ MI(PS) exposure condition was a slightly poorer predictor of lung damage than MI. Finally, the lungs of six adult crossbred pigs were exposed at the highest amplitude exposure levels permitted by a diagnostic ultrasound system (to prevent probe damage) at both frequencies; no lung damage was observed which suggests the possibility of a species dependency biological effect.