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Cavitation events generated during histotripsy therapy generate large acoustic cavitation emission (ACE) signals that can be detected through the skull. This article investigates the feasibility of using these ACE signals, acquired using the elements of a 500-kHz, 256-element hemispherical histotripsy transducer as receivers, to localize and map the cavitation activity in real time through the human skullcap during transcranial histotripsy therapy. The locations of the generated cavitation events predicted using the ACE feedback signals in this study were found to be accurate to within <1.5 mm of the centers of masses detected by optical imaging and found to lie to within the measured volumes of the generated cavitation events in $ {\gtrsim 80}$ % of cases. Localization results were observed to be biased in the prefocal direction of the histotripsy array and toward its transverse origin but were only weakly affected by focal steering location. The choice of skullcap and treatment pulse repetition frequency (PRF) were both observed to affect the accuracy of the localization results in the low PRF regime (1–10 Hz), but the localization accuracy was seen to stabilize at higher PRFs (≥10 Hz). Tests of the localization algorithm in vitro, for treatment delivered to a bovine brain sample mounted within the skullcap, revealed good agreement between the ACE feedback-generated treatment map and the morphological characteristics of the treated volume of the brain sample. Localization during experiments was achieved in real time for pulses delivered at rates up to 70 Hz, but benchmark tests indicate that the localization algorithm is scalable, indicating that higher rates are possible with more powerful hardware. The results of this article demonstrate the feasibility of using ACE feedback signals to localize and map transcranially generated cavitation events during histotripsy. Such capability has the potential to greatly simplify transcranial histotripsy treatments, as it may provide a non-MRI-based method for monitoring and localizing transcranial histotripsy treatments in real time. [ABSTRACT FROM AUTHOR]

Residual bubbles produced after collapse of a cavitation cloud provide cavitation nuclei for subsequent cavitation events, causing cavitation to occur repeatedly at the same discrete set of sites. This effect, referred to as cavitation memory, limits the efficiency of histotripsy soft tissue fractionation. Besides passively mitigating cavitation memory by using a low pulse repetition frequency (~1 Hz), an active strategy was developed by our group. In this strategy, low-amplitude ultrasound sequences were used to stimulate coalescence of residual bubbles. The goal of this work is to remove cavitation memory and achieve rapid, homogeneous lesion formation using a single phased array transducer. A 1-MHz integrated histotripsy and bubble coalescing (BC) transducer system with a specialized electronic driving system was built in house. High-amplitude ($P- >= 30$ MPa) histotripsy pulses and subsequent low-amplitude (~1–2 MPa) BC sequences were applied to a red blood cell tissue-mimicking phantom at a single focal site. Significant reduction of the cavitation memory effect and increase in the fractionation rate were observed by introducing BC sequence. Effects of BC pulsing parameters were further studied. The optimal BC parameters were then utilized to homogenize a $10 \times 10$ mm2 region at high rate. [ABSTRACT FROM AUTHOR]

Histotripsy is a non-invasive, non-thermal ablation technique that uses high-amplitude, focused ultrasound pulses to fractionate tissue via acoustic cavitation. The goal of this study was to illustrate the potential of histotripsy with electronic focal steering to achieve rapid ablation of a tissue volume at a rate matching or exceeding those of current clinical techniques (∼1-2 mL/min). Treatment parameters were established in tissue-mimicking phantoms and applied to ex vivo tissue. Six-microsecond pulses were delivered by a 250-kHz array. The focus was electrically steered to 1000 locations at a pulse repetition frequency of 200 Hz (0.12% duty cycle). Magnetic resonance imaging and histology of the treated tissue revealed a distinct region of necrosis in all samples. Mean lesion volume was 35.6 ± 4.3 mL, generated at 0.9-3.3 mL/min, a speed faster than that of any current ablation method for a large volume. These results suggest that histotripsy has the potential to achieve non-invasive, rapid, homogeneous ablation of a tissue volume. [ABSTRACT FROM AUTHOR]

This study investigates the safety profile for use of histotripsy, a non-invasive ultrasonic ablation method currently being developed for the treatment of liver cancer, for liver ablation in an in vivo porcine model. Histotripsy treatments were applied to the liver and hepatic veins of 22 porcine subjects, with half of the subjects receiving systemic heparinization. Vital signs (heart rate, blood pressure, temperature, electrocardiogram and SpO2) were monitored throughout the procedure and for 1 h post-treatment. Blood was drawn at six points during the experiment to analyze blood gases, liver function and free hemoglobin levels. All treatments were guided and monitored by real-time ultrasound imaging. After treatment, the tissue was harvested for histological analysis. Results indicated that histotripsy generated well-defined lesions inside the liver and around the treated hepatic veins of all subjects in both treatment groups. Vital signs and blood analysis revealed that animals responded well to histotripsy, with all animals surviving the treatment. One animal in the non-heparinized group had a transient increase in pH and decreases in blood pressure, heart rate and PCO2 during the 15-min vessel treatment, with these changes returning to baseline levels soon after the treatment. Overall, the results indicate that histotripsy can safely be performed on the liver without the need for systemic heparinization, even in regions containing large hepatic vessels, supporting its future use for the treatment of liver cancer. [ABSTRACT FROM AUTHOR]