High speed imaging of bubble clouds generated in pulsed ultrasound cavitational therapy-histotripsy

Our recent studies have demonstrated that mechanical fractionation of tissue structure with sharply demarcated boundaries can be achieved using short (< 20 mu s), high intensity ultrasound pulses delivered at low duty cycles. We have called this technique histotripsy. Histotripsy has potential clinical applications where noninvasive tissue fractionation and/or tissue removal are desired. The primary mechanism of histotripsy is thought to be acoustic cavitation, which is supported by a temporally changing acoustic backscatter observed during the histotripsy process. In this paper, a fast-gated digital camera was used to image the hypothesized cavitating bubble cloud generated by histotripsy pulses. The bubble cloud was produced at a tissue-water interface and inside an optically transparent gelatin phantom which mimics bulk tissue. The imaging shows the following: 1) Initiation of a temporally changing acoustic backscatter was due to the formation of a bubble cloud; 2) The pressure threshold to generate a bubble cloud was lower at a tissue-fluid interface than inside bulk tissue; and 3) at higher pulse pressure, the bubble cloud lasted longer and grew larger. The results add further support to the hypothesis that the histotripsy process is due to a cavitating bubble cloud and may provide insight into the sharp boundaries of histotripsy lesions.