Aberration Correction for Histotripsy Ablation of Liver

Abstract Histotripsy is an ultrasound surgical technique for non-invasive ablation of tissue that uses very intense bursts of focused acoustic energy to mechanically fracture tissue through cavitation. A pilot clinical trial for liver ablation has shown safety, efficacy, and good tolerance by patients while larger multi-site trials are currently underway. This proposal seeks to solve two key limitations with current technology that will hinder widespread clinical use of histotripsy ablation for a diverse range of patients. The first is targeting. Cavitation bubbles producing the histotripsy therapeutic effect are directly visible with high sensitivity and contrast on ultrasound imaging. However, prior to the initiation of therapy, the precise target location has an uncertainty on the order of several millimeters due to refraction of the acoustic field from variations in sound speed. Aim 1 achieves this goal by developing an ultrasound imaging sequence to directly visualize the histotripsy focus without producing cavitation. The second limitation is aberration. In addition to focal shifts from refraction, tissue sound speed heterogeneity reduces the peak amplitude of a histotripsy sound field. Measurements and acoustic simulations show significant amplitude reductions that would be recovered using aberration correction (AC) techniques. Simulations further suggest that even the highest performance transducer technology will have a limited treatment envelope when targeting a diverse range of patients. For aim 2, we will optimize an AC technique for histotripsy to recover this lost focal pressure and determine the best practices for use when ablating tissue volumes . For aim 3, we will validate both techniques in human cadavers and use the results to calibrate further acoustic simulations. Calibrated simulations will allow comprehensive studies in a diverse range of subjects and facilitate designing the next generation of optimized transducer arrays for histotripsy ablation.