Thresholds for Hemorrhages in Mouse Skin and Intestine Induced by Lithotripter Shock Waves

In vivo biological effects of ultrasound should be characterized as thermal or cavitational to understand their etiology and significance. A spark-gap shock-wave lithotripter was built and used to compare cavitation-induced hemorrhages to the heat-induced petechial hemorrhages caused by continuous-wave ultrasound in mouse intestine. Intestinal hemorrhages induced in anesthetized hairless mice by the lithotripter pulses involved tissue destruction with bleeding into the lumen of the intestine, and were associated with intestinal gas bubbles. Skin hemorrhages were also observed, which appeared to be contusions, with no actual breakage of the skin. Administration of 100 shock waves with peak positive amplitude of 18.5 MPa produced an average of 7.6 (standard error [SE] 3.1, n = 6) intestinal hemorrhages and 45 (SE 11) skin hemorrhages. The counts and severity of hemorrhages increased with increasing numbers (3 to 300) of shock waves. Absorbers of varying thickness were used to reduce the pressure amplitude of the shock waves, which were thereby modified into low frequency ultrasound pulses. For 100 pulse exposures, apparent thresholds for effects occurred between 1.6 and 4.0 MPa for the intestinal hemorrhages and between 0.6 and 1.6 MPa for the skin hemorrhages. The low 1-Hz pulse repetition frequency precluded significant heating, and so these effects were the result of cavitation, which probably occurred inside the intestines or in the surrounding water. Compared to the previously observed thermal petechia, the cavitation-induced hemorrhages could be distinguished on the basis of their appearance upon histological examination, and also by the relative values of the thermal and mechanical exposure indices associated with the two different exposure modes.