Bioeffects of positive and negative acoustic pressures in mice infused with microbubbles

Abstract This study provided one test of the hypothesis that hemorrhage in tissues containing ultrasound (US) contrast agents results from inertial cavitation. The test relied on the prediction of classical cavitation theory that the response of microbubbles to negative pressures is much greater than it is for positive pressures. An endoscopic electrohydraulic lithotripter was used to generate a spherically diverging positive pressure pulse. A negative pressure pulse was produced by reflection of the positive pulse from a pressure release interface. Mice were injected with ≈0.1 mL of Albunex® and exposed to 100 pulses at either + 3.6 MPa or −3.6 MPa pressure amplitude. For comparison, mice were also exposed to the same acoustic fields without injection of contrast agents. Sham animals experienced the same protocols, with or without Albunex® injections, but were not exposed to the lithotripter fields. Following exposure, mice were scored for hemorrhage to various organs and tissues. When Albunex® was present in the vasculature, negative pressure pulses produced significantly more hemorrhage than positive pressures in tissues such as the kidney, intestine, skin, muscle, fat, mesentery and stomach.