High-speed observations of Acoustic Cluster Therapy “activation” and “therapy”

Abstract

Acoustic Cluster Therapy (ACTTM) is a novel and versatile drug delivery platform, based on electrostatically bound clusters of negatively charged contrast agent microbubbles (SonazoidTM, GE Healthcare) and positively charged oil microdroplets, for co-administration with drug to the vasculature. Preliminary in-vitro high-speed observations at up to 10 million frames per second of both “activation” (exposure of clusters to 2.19 MHz focused ultrasound, at mechanical index, MI ≈ 0.15) and “therapy” (exposure of the resulting vapour bubbles, to 675 kHz with MI ranging from 0.1 to 0.4) will be presented. At low MI, the therapy exposure induces quasi-linear oscillations of the vapour bubble, with higher MIs inducing high-order surface wave activity. In the latter case, the amplitude of the non-spherical oscillations increase during the exposure until involutions neck, generating intra-bubble droplets that traverse the bubble core at speeds of up to several m/s. Possible mechanisms for activation and therapy will be discussed, based on the observations. [This research was supported by ERC Starting Grant TheraCav, 336189, and Glasgow Knowledge Exchange project DefACT.]