The role of compressional pressure in the formation of dense bubble clouds in histotripsy

Histotripsy is a non-invasive ultrasound therapy which utilizes cavitation clouds to mechanically fractionate tissue. The mechanism by which bubble clouds form is important to understand the histotripsy process. We used high speed imaging with frame rates between 0.1-10 million fps to observe the progression of cloud formation. A 1 MHz spherically-focused transducer was used to apply single histotripsy pulses to optically-transparent gelatin tissue phantoms, with peak negative pressure of 19 MPa and 5-50 cycles. Dense bubble clouds were observed to first form at a distal position within the focus, and grow proximally towards the transducer, opposite the ultrasound propagation direction. Growth began from the site of single cavitation bubbles. Based on these observations, it was hypothesized that the shocked waveforms from histotripsy pulses scatter from single bubbles, which invert the shock and induce a large negative pressure in its vicinity. To test this hypothesis, the positive incident shock pressure was reduced without significantly affecting the negative pressure. When the peak positive pressure was lowered, the likelihood and size of bubble clouds initiating at the focus was greatly reduced. These results suggest that the positive pressure of the incident waveform is important for generating bubble clouds in histotripsy.