Non-linear acoustic emissions from therapeutically driven microbubbles

Abstract

Acoustic detection of contrast agent microbubbles, infused to the vasculature for exposure to focused ultrasound, is now routinely undertaken to evaluate therapy and avoid irreversible tissue damage. Harmonic, subharmonic (to the frequency of the focused ultrasound, f0) and broadband emissions are often used to distinguish between stable and inertial cavitation activity, and associated bioeffects. The driven microbubble dynamic responsible for the generation of non-linear emissions, however, may not be well understood. Results from an investigation of single SonoVue microbubbles flowing through a capillary, for exposure to focused ultrasound at f0 = 692 kHz, will be presented. Dual high-speed imaging from orthogonal perspectives at circa 2 × 105, and shadowgraphically at 10 million frames per second, capture microbubble activity and shock wave generation. Acoustic emissions are simultaneously collected with a calibrated broadband needle hydrophone, and high frequency imaging array on passive receive, for cavitation mapping. The results indicate that non-linear emissions are mediated by periodic bubble collapse shock waves, with subharmonic emission occurring above a threshold driving pressure amplitude. Implications for detection and quantification of driven microbubble cavitation activity, as well as conventional classification as stable or inertial, will be discussed. [This work was supported by ERC Starting Grant TheraCav, 336189.]