Superthreshold behavior and threshold estimation of ultrasound-induced lung hemorrhage in adult mice and rats

Threshold estimates and superthreshold behaviors for ultrasound-induced lung hemorrhage were investigated as a function of species (adult mice and rats) and ultrasound frequency (2.8 and 5.6 MHz). A total of 151 6-to-7-week-old female ICR mice and 160 10-to-11-week-old female Sprague-Dawley rats were randomly divided into two ultrasonic frequency groups, and further randomly divided into seven or eight ultrasonic peak rarefactional pressure groups. Each group consisted of about 10 animals. Animals were exposed to pulsed ultrasound at either 2.8-MHz center frequency (1-kHz PRF, 1.42-microsecond pulse duration) or 5.6-MHz center frequency (1-kHz PRF, 1.17-microsecond pulse duration) for a duration of 10 seconds. The in situ (at the pleural surface) peak rarefactional pressure levels ranged between 2.5 and 10.5 MPa for mice and between 2.3 and 11.3 MPa for rats. The mechanical index (MI) ranged between 1.4 and 6.3 at 2.8 MHz for mice and between 1.1 and 3.1 at 5.6 MHz for rats. The lesion surface area and depth were measured for each animal as well as the percentage of animals with lesions per group. The characteristics of the lesions produced in mice and rats were similar to those described in previous studies by our research group and others, suggesting a common pathogenesis in the initiation and propagation of the lesions at the gross and microscopic levels. The percentage of animals with lesions showed no statistical differences between species or between ultrasound frequencies. These findings suggest that mice and rats are similar in sensitivity to ultrasound-induced lung damage and that the occurrence of lung damage is independent of frequency. Lesion depth and surface area also showed no statistically significant differences between ultrasound frequencies for mice and rats. However, there was a significant difference between species for lesion area and a suggestive difference between species for lesion depth. The superthreshold behavior of lesion area and depth showed that rat lung had more damage than mouse lung, and the threshold estimates showed a weak, or lack of, frequency dependency, suggesting that the MI is not consistent with the observed findings.