Role of pulse repetition frequency and exposure duration on the superthreshold behavior of ultrasound-induced lung hemorrhage in adult mice and rats

Superthreshold behavior for ultrasound-induced lung hemorrhage was investigated in 150 mice and 150 rats at 2.8 MHz to assess the role of pulse repetition frequency (PRF) and exposure duration (ED). Each species was divided into 15 exposure groups (10 per group) for a 3×5 randomized factorial design (3 EDs of 5, 10 and 20 s; and 5 PRFs of 25, 50, 100, 250 and 500 Hz). The in situ peak rarefactional pressure (12.3 MPa) and pulse duration (1.42 μs) were the same for all ultrasonically exposed animals. Also, for both species, 15 sham-exposed animals were randomized into both studies, none of which had lesions. Factorial analysis of variance was used to evaluate effects of PRF and ED on the proportion of lesions, lesion depth and lesion surface area. The proportion of lesions in both species was related statistically to PRF and ED, with the exception that PRF in rats was not quite significant. The PRF, but not ED, significantly affected lesion depth in both species. Both PRF and ED significantly affected lesion surface area in mice, while neither affected area in rats. The PRF×ED interaction (number of pulses) for these measures was not significant for either species. Species significantly affected lesion production and size; there were fewer lesions in mice, and the lesion size was greater in rats. The characteristics of the lesions produced in both species were similar to those described in studies by our research group and others, suggesting a common pathogenesis for the initiation and propagation of the lesions at the gross and microscopic levels.