Ultrasound-induced lung hemorrhage is not caused by inertial cavitation

In animal experiments, the pathogenesis of lung hemorrhage due to exposure to clinical diagnostic levels of ultrasound has been attributed to an inertial cavitation mechanism. The purpose of this article is to report the results of two experiments that directly contradict the hypothesis that ultrasound-induced lung hemorrhage is caused by inertial cavitation. Elevated hydrostatic pressure was used to suppress the involvement of inertial cavitation. In experiment one, 160 adult mice were equally divided into two hydrostatic pressure groups (0.1 or 1.1 MPa), and were randomly exposed to pulsed ultrasound (2.8-MHz center frequency, 1-kHz PRF, 1.42-μs pulse duration, 10-s exposure duration). For the two hydrostatic pressure groups (80 mice each), 8 in situ peak rarefactional pressure levels were used that ranged between 2.82 and 11.8 MPa (10 mice/group). No effect of hydrostatic pressure on the probability of hemorrhage was observed. These data lead to the conclusion that lung hemorrhage is not caused by inertial cavitation. Also, the higher hydrostatic pressure enhanced rather than inhibited the impact of ultrasonic pressure on the severity (hemorrhage area, depth, and volume) of lesions. These counterintuitive findings were confirmed in a second experiment using a $\text{2×5}$ factorial design that consisted of two ultrasonic pressure levels and five hydrostatic pressure levels (100 mice, 10 mice/group). If inertial cavitation were the mechanism responsible for lung hemorrhage, then elevated hydrostatic pressures should have resulted in less rather than more tissue damage at each ultrasonic pressure level. This further supports the conclusion that the pathogenesis of ultrasound-induced lung hemorrhage is not caused by inertial cavitation.