In vivo histotripsy brain treatment.

OBJECTIVE: Histotripsy is an ultrasound-based treatment modality relying on the generation of targeted cavitation bubble clouds, which mechanically fractionate tissue. The purpose of the current study was to investigate the in vivo feasibility, including dosage requirements and safety, of generating well-confined destructive lesions within the porcine brain utilizing histotripsy technology. METHODS: Following a craniectomy to open an acoustic window to the brain, histotripsy pulses were delivered to generate lesions in the porcine cortex. Large lesions with a major dimension of up to 1 cm were generated to demonstrate the efficacy of histotripsy lesioning in the brain. Gyrus-confined lesions were generated at different applied dosages and under ultrasound imaging guidance to ensure that they were accurately targeted and contained within individual gyri. Clinical evaluation as well as MRI and histological outcomes were assessed in the acute (≤ 6 hours) and subacute (≤ 72 hours) phases of recovery. RESULTS: Histotripsy was able to generate lesions with a major dimension of up to 1 cm in the cortex. Histotripsy lesions were seen to be well demarcated with sharp boundaries between treated and untreated tissues, with histological evidence of injuries extending ≤ 200 µm from their boundaries in all cases. In animals with lesions confined to the gyrus, no major hemorrhage or other complications resulting from treatment were observed. At 72 hours, MRI revealed minimal to no edema and no radiographic evidence of inflammatory changes in the perilesional area. Histological evaluation revealed the histotripsy lesions to be similar to subacute infarcts. CONCLUSIONS: Histotripsy can be used to generate sharply defined lesions of arbitrary shapes and sizes in the swine cortex. Lesions confined to within the gyri did not lead to significant hemorrhage or edema responses at the treatment site in the acute or subacute time intervals.

Non-Invasive Liver Ablation Using Histotripsy: Preclinical Safety Study in an In Vivo Porcine Model.

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.

Histotripsy of the prostate using a commercial system in a canine model.

PURPOSE: Histotripsy is a focused ultrasound technology that uses controlled acoustic cavitation to homogenize targeted tissue. We assessed local and systemic effects after histotripsy treatment with the Vortx RX® system in a canine model. The system was not approved for human use at the time of the study. MATERIALS AND METHODS: Histotripsy was applied in 10 intact male dogs. The therapy transducer (36 elements, 700 kHz and 11 cm focal distance) delivered acoustic bursts (3 cycles and 500 Hz pulse repetition frequency) transabdominally to the prostate for 60 minutes. Tissue and systemic response were assessed by transrectal ultrasound, cystoscopy and interval evaluation of blood and urine parameters. Prostates were harvested on postoperative day 2 in 2 dogs and on postoperative day 28 in 8. RESULTS: A treatment cavity was apparent in each prostate on transrectal ultrasound and cystoscopy. Mean prostate volume decreased 36% (range 19% to 53%) by postoperative day 28. Although clinical symptoms were not produced, notable pathological findings at necropsy consisted of rectal wall muscle degeneration in 2 animals and concern for a potential histotripsy effect and 1 cm diameter areas of fibrosis in the abdominal rectus muscle in 2 animals suggestive of thermal injury along the acoustic propagation path to the prostate. CONCLUSIONS: Extracorporeal application of histotripsy produced prostate debulking in all dogs. Pathological findings of collateral injury are of concern since this may represent suboptimal confinement of cavitation or heating of overlying tissue. Further study is under way to quantify the prefocal thermal fields to eliminate these effects before human application.