Detection of acoustic cavitation in the heart with microbubble contrast agents in vivo: A mechanism for ultrasound-induced arrhythmias

Ultrasound fields can produce premature cardiac contractions under appropriate exposure conditions. The pressure threshold for ultrasound-induced premature contractions is significantly lowered when microbubble contrast agents are present in the vasculature. The objective of this study was to measure directly ultrasound-induced cavitation in the murine heart in vivo and correlate the occurrence of cavitation with the production of premature cardiac contractions. A passive cavitation detection technique was used to quantify cavitation activity in the heart. Experiments were performed with anesthetized, adult mice given intravenous injections of either a contrast agent (Optison®) or saline. Murine hearts were exposed to ultrasound pulses (200kHz, 1ms, 0.1–0.25MPa). Premature beats were produced in mice injected with Optison®and the likelihood of producing a premature beat increased with increasing pressure amplitude. Similarly, cavitation was detected in mice injected with Optison® and the amplitude of the passive cavitation detector signal increased with increasing exposure amplitude. Furthermore, there was a direct correlation between the extent of cavitation and the likelihood of ultrasound producing a premature beat. Neither premature beats nor cavitation activity were observed in animals injected with saline and exposed to ultrasound. These results are consistent with acoustic cavitation as a mechanism for this bioeffect.