Abstract

Histotripsy is a tissue ablation method that utilizes focused, high-amplitude ultrasound to generate a cavitation bubble cloud that mechanically fractionates tissue. Effective histotripsy depends on the initiation, control, and maintenance of cavitation bubble clouds in the targeted area. In this study, we hypothesized that a low-pressure acoustic pulse sequence applied before and/or during histotripsy therapy would increase the cavitation initiation pressure threshold and the growth of cavitation bubble clouds. This technique could shrink or "sharpen" the focal zone during histotripsy to produce more precise and well-defined lesions with minimal collateral damage. It may also be a way to actively protect the soft tissue from cavitation damage during lithotripsy by increasing the pressure threshold for bubble cloud initiation. We applied these low-amplitude acoustic pulse sequences before and during histotripsy treatments with the pulse repetition frequency of 1 and 100 Hz, in three different mediums: water, tissue phantom agarose gel, and bovine liver in vitro. Acoustic backscatter signals and optical imaging were used to detect and monitor the initiation, maintenance, and growth of the resulting cavitation bubble cloud. The results demonstrated that the use of low-amplitude acoustic pulse sequences could increase the cavitation pressure amplitude threshold by 20% in the targeted area.

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