Superthreshold behavior of ultrasound-induced lung hemorrhage in adult rats: role of pulse repetition frequency and pulse duration.

Ultrasound-induced lung hemorrhage is a well-documented in vivo bioeffect in mice,1–12 rats,11–20 monkeys,21 rabbits,7,8 and pigs.7,8,22–25 Acoustic pressure lung hemorrhage thresholds have been estimated in mice,1,4–6,9,12 rats,11,12,14,17 rabbits, and pigs.23–25 From these threshold studies, the pressure thresholds appear to be the same for mice, rats, and rabbits; pressure thresholds do not appear different as a function of frequency or beam width for mice and rats; pressure thresholds have a significant pulse duration (PD) trend for rats; and virtually every pressure threshold (normalized to the mechanical index [MI]) is less than the US Food and Drug Administration (FDA) regulatory limit (MI < 1.926). Also, at superthreshold exposure conditions (in situ [at the pleural surface] peak rarefactional pressure, pr(in situ), = 6.1 MPa), a 3 × 3 factorial design study (pulse repetition frequency [PRF]: 17, 170, and 1700 Hz; exposure duration [ED]: 5, 31.6, and 200 s) showed that the main effects of PRF and ED were not significant for lesion occurrence and sizes, whereas the interaction term (PRF × ED; total number of pulses) was highly significant.18 These findings do not suggest, however, that PRF and ED did not have an effect. Rather, if either PRF or ED is held relatively constant, or varied over only a narrow range, then the number of pulses will appear as an effect of the nonconstant variable. These findings are consistent with those1 that showed a slightly larger proportion of mice with lesions for 100-Hz PRF compared to 10-Hz PRF. In general, however, the effect of exposure timing quantities (PD, ED, and PRF) on the threshold for ultrasound-induced lung hemorrhage and on the size of the lesions at superthreshold levels has been examined only to a limited extent. So far, only the interaction of PRF and ED has been examined. The interaction of PRF and PD has not been examined and thus is the purpose of this study for which the interaction term (PRF × PD) is the duty factor, the fractional amount of time the pulse is excited. Furthermore, this factorial PRF × PD study is an adjunct to the previously reported PD threshold study for which the PRF was held constant.17