High resolution ultrafast imaging of microbubble destruction during sonoporation

Ultrasound-mediated drug delivery using microbubbles is a growing field with applications ranging from targeted chemotherapy to permeating the blood brain barrier. Despite the potential clinical impact of this technique, the precise parameters needed to reliably induce cell sonoporation, or increased cellular permeability, are not well understood. The goal of this work is to use high frame rate imaging to visualize bubble destruction and propagation in order to extrapolate the parameters of importance in performing in vitro sonoporation. Through this work, it was observed that acoustic shadowing occurs at high microbubble concentrations (>1M bubbles/ml), which inhibits ultrasound delivery to bubbles next to cells. Pressure attenuation was observed to dramatically increase with increasing microbubble concentration. Unique microbubble destruction patterns shown with high resolution, ultrafast imaging included streaming, vortexing and standing waves. The complexity of the microbubble destruction patterns during sonication as observed for the first time with high resolution ultrafast imaging will provide guidance on how to achieve reliable sonoporation.