Changes in bubble-cloud dissolution throughout the application of histotripsy pulses

Material damage is a consideration for any applications where pressure fields may initiate cavitation. Histotripsy is a focused ultrasound therapy that exploits the destructive property of bubble clouds to disrupt viscoelastic tissue. The resulting effect achieves the same outcomes as surgery without the need for an invasive procedure. This study investigated the relationship between changes in bubble clouds throughout focused ultrasound exposure. Specifically, the dissolution period of bubbles generated in water and agarose gel was tracked with ultrafast ultrasound imaging. This imaging marker was found to increase in agarose during the initial stages of exposure, and maintained steady-state values after 555 ± 64 applied histotripsy pulses. The relative change in damage area of the gel and bubble-dissolution period with exposure duration were found to be equivalent (p > 0.05). Acoustic emissions tracked with passive acoustic imaging were also evaluated and were found to have a different functional form with exposure duration than the bubble-dissolution period or area of damage to the gel. In contrast, there were no noted changes in these imaging markers throughout histotripsy exposure when bubble clouds were generated in water. A previously validated bubble-dynamics model was extended to calculate the anticipated changes to bubble expansion during histotripsy exposure under the assumption that the agarose elastic modulus approached 0 kPa (i.e., total fractionation). The calculations predicted larger changes in the bubble dynamics than was observed, which might reflect complicated dynamics of the bubble cloud during the final stages of treatment.