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Histotripsy is an ultrasound ablation method that depends on the initiation of a dense cavitation bubble cloud to fractionate soft tissue. Previous work has demonstrated that a cavitation cloud can be formed by a single acoustic pulse with one high-amplitude negative cycle, when the negative pressure amplitude exceeds a threshold intrinsic to the medium. The intrinsic thresholds in soft tissues and tissue phantoms that are water based are similar to the intrinsic threshold of water over an experimentally verified frequency range of 0.3–3 MHz. Previous work studying the histotripsy intrinsic threshold has been limited to experiments performed at room temperature (~20°C). In this study, we investigate the effects of temperature on the histotripsy intrinsic threshold in water, which is essential to accurately predict the intrinsic thresholds expected over the full range of in vivo therapeutic temperatures. Based on previous work studying the histotripsy intrinsic threshold and classical nucleation theory, we hypothesize that the intrinsic threshold will decrease with increasing temperature. To test this hypothesis, the intrinsic threshold in water was investigated both experimentally and theoretically. The probability of generating cavitation bubbles was measured by applying a single pulse with one high-amplitude negative cycle at 1 MHz to distilled degassed water at temperatures ranging from 10 °C to 90 °C. Cavitation was detected and characterized by passive cavitation detection and high-speed photography, from which the probability of cavitation was measured versus pressure amplitude. The results indicate that the intrinsic threshold (the negative pressure at which the cavitation probability $=\,0.5$ ) significantly decreases with increasing temperature, showing a nearly linear decreasing trend from 29.8 ± 0.4 MPa at 10 °C to 14.9±1.4 MPa at 90 °C. Overall, the results of this study support our hypothesis that the intrinsic threshold is highly dependent on the temperature of the medium, which may allow for better predictions of cavitation generation at body temperature in vivo and at the elevated temperatures commonly seen in high-intensity focused ultrasound regimes. [ABSTRACT FROM PUBLISHER]

Shock wave lithotripsy (SWL) suffers from the fact that it can produce residual stone fragments of significant size (>2 mm). Mechanistically, cavitation has been shown to play an important role in the reduction of such fragments to smaller debris. In this study, we assessed the feasibility of using cavitationally-based pulsed ultrasound therapy (histotripsy) to erode kidney stones. Previous work has shown that histotripsy is capable of mechanically fractionating soft tissue into fine, acellular debris. Here, we investigated the potential for translating this technology to renal calculi through the use of a commonly accepted stone model. Stone models were sonicated using a 1-MHz focused transducer, with 5-cycle pulses delivered at a rate of 1 kHz. Pulses having peak negative pressures ranging from 3 to 21 MPa were tested. Results indicate that histotripsy is capable of effectively eroding the stone model, achieving an average stone erosion rate of 26 mg/min at maximum treatment pressure; substantial stone erosion was only observed in the presence of a dense cavitational bubble cloud. Sequential sieving of residual stone fragments indicated that debris produced by histotripsy was smaller than 100 μm in size, and treatment monitoring showed that both the cavitational bubble cloud and model stone appear as hyperechoic regions on B-mode imaging. These preliminary results indicate that histotripsy shows promise in its use for stone comminution, and an optimized erosion process may provide a potential adjunct to conventional SWL procedures.