Histotripsy Fractionation of Prostate Tissue: Local Effects and Systemic Response in a Canine Model

Abstract

Histotripsy is an extracorporeal ultrasound technology that uses cavitational mechanisms to produce nonthermal tissue destruction. Previously we reported the feasibility of histotripsy for prostate tissue fractionation and immediate debulking. In this study we characterized the local effects and systemic response after histotripsy treatment of prostate tissue in an in vivo canine model. Histotripsy was applied transabdominally to the prostate in 18 intact male canine subjects under general anesthesia. Acoustic bursts (4 μseconds) were delivered at a 300 Hz pulse repetition rate from a highly focused 750 kHz piezoelectric ultrasound transducer with a 15 cm aperture and 3 × 3 × 8 mm focal volume. Specimens of the prostate and surrounding structures were obtained at prescribed time points (0, 7, 28 or 56 days) after histotripsy. Blood and urine parameters were assessed periodically while clinical evaluation incorporating a validated veterinary pain scale was performed daily. Conventional transrectal ultrasound facilitated targeting of the focal volume and provided real-time assessment of cavitation activity. Fractionation of the targeted volume and clearance of the resultant debris with urination produced a treatment cavity in each prostate. No acoustic collateral damage was seen and urothelialization of the treatment cavity developed within 28 days of treatment. Only transient laboratory value abnormalities and minimal hematuria were noted after treatment. Pain scores revealed only mild posttreatment discomfort. Histotripsy produced consistent tissue fractionation and prostate debulking without collateral acoustic injury or clinical side effects and it was well tolerated in the canine model.