Non-linear acoustic emissions from therapeutically driven contrast agent microbubbles

Non-linear emissions from microbubbles introduced to the vasculature for exposure to focused ultrasound are routinely monitored for assessment of therapy and avoidance of irreversible tissue damage. Yet the bubble-based mechanistic source for these emissions, under subresonant driving at typical therapeutic pressure amplitudes, may not be well understood. In the study described here, dual-perspective high-speed imaging at 210,000 frames per second (fps), and shadowgraphically at 10 Mfps, was used to observe cavitation from microbubbles flowing through a 500-µm polycarbonate capillary exposed to focused ultrasound of 692 kHz at therapeutically relevant pressure amplitudes. The acoustic emissions were simultaneously collected via a broadband calibrated needle hydrophone system. The observations indicate that periodic bubble-collapse shock waves can dominate the non-linear acoustic emissions, including subharmonics at higher driving amplitudes. Contributions to broadband emissions through variance in shock wave amplitude and emission timings are also identified. Possible implications for in vivo microbubble cavitation detection, mechanisms of therapy and the conventional classification of cavitation activity as stable or inertial are discussed.