Contrast agent microbubble scattering in response to sub-resonant ultrasonic driving

Abstract

Much of the literature describing contrast agent microbubble response to ultrasound, details exposure to frequencies of 1 MHz, or above. The application of microbubble-mediated and transcranial focused ultrasound therapy of the brain, however, is clinically administered at 220 kHz to achieve adequate transmission across the skull. This excitation frequency is an order of magnitude below accepted values for microbubble resonances, yet fundamental studies of such sub-resonantly driven microbubble activity have only recently started to emerge. In this presentation our recent high-speed imaging-based investigations of single and multiple clinically approved microbubbles, exposed to sub-MHz focused ultrasound, will be reviewed. The observations indicate that the well documented microbubble response to higher frequencies, may not be applicable to lower frequency therapeutic driving. Specifically, periodic bubble-collapse generated pressure impulses are shown to account for all non-linear scattering, including subharmonics, harmonics and broadband noise, dependent on the amplitude of the driving [Song et al., in UMB (2019)]. A new mechanism for microbubble-jetting, which occurs spontaneously on interaction between the microbubble at first inflation, and the pressure gradients within the initial cycles of a burst of sub-MHz focused ultrasound, will also be described [Cleve et al., in UMB (2019)].