Estimating the mechanical energy of histotripsy bubble clouds with high frame rate imaging

Mechanical ablation with the focused ultrasound therapy histotripsy relies on the generation and action of bubble clouds. Despite its critical role for ablation, quantitative metrics of bubble activity to gauge treatment outcomes are still lacking. Here, plane wave imaging was used to track the dissolution of bubble clouds following initiation with the histotripsy pulse. Information about the rate of change in pixel intensity was coupled with an analytic diffusion model to estimate bubble size. Accuracy of the hybrid measurement/model was assessed by comparing the predicted and measured dissolution time of the bubble cloud. Good agreement was found between predictions and measurements of bubble cloud dissolution times in agarose phantoms and murine subcutaneous SCC VII tumors. The analytic diffusion model was extended to compute the maximum bubble size as well as energy imparted to the tissue due to bubble expansion. Regions within tumors predicted to have undergone strong bubble expansion were collocated with ablation. Further, the dissolution time was found to correlate with acoustic emissions generated by the bubble cloud during histotripsy insonation. Overall, these results indicate a combination of modeling and high frame rate imaging may provide means to quantify mechanical energy imparted to the tissue due to bubble expansion for histotripsy.