ИСТИНА

Prostate cancer (PCa)focal therapy with high intensity focused ultrasound (HIFU) aims for oncologic control while minimizing morbidity.However, current clinical transrectal HIFU systems have limitations related to the relatively slow heating and limited real-time monitoring which could prevent optimal clinical outcomes. Boiling histotripsy (BH) is a HIFU methodthat uses milliseconds-long (<20 ms) pulses at low-duty cycle to mechanically ablate tissue.Our group is developing BH as anovel transrectal focal therapy for PCa. Owing to the rapidity of tissue bioeffeсts and the mechanical mechanism of action, BH minimizes heat-sink effects and thermal spread that complicate thermal treatment, while allowing for real-time ultrasound (US) feedback due to generation of bubbles.Here we aimed to evaluate the feasibility of BH ablation of human ex vivo prostate tissue as a proof of principal. Fresh human prostate tissuewas obtained via rapid autopsy (<12 hours after death,n=4) using an IRB approved procurement program. Tissue was degassed and then embedded in low melting point agar gel. Under US guidance, BH pulses (5 ms duration, 2 Hz pulse repetition frequency, peak focal pressures of p+=88 MPa, p-=17 MPa, 200 pulses/focus) were delivered to a rectangular grid(6 x 6 mm with 2 mm spacing) within tissue samples using a 1.5-MHz custom-made transducer (80 mm diameter and 60 mm focal length). Following the treatment, tissue was evaluated grossly or formalin-fixed for histologic assessment with H&E staining. During treatment,BH produced the expected hyperechoic bubbles at the focus in all irradiated tissue suggesting treatment success. On gross assessment, small non-blanched fluid filled lesions spaced ~2 mm apart were observed consistent with mechanical ablation. On histological analysis, lesionscontainingpockets of completely homogenizedcell debris were observed consistent with histotripsy induced mechanical ablation of glandular elements. These pockets were intermixed with regions of intact smooth muscle and collagen fibrils consistent with sparing of fibromuscular elements. This data represents the first successful application of BH in ex vivo human prostate tissue and suggests that BH mechanical prostate ablation is feasible. Further work is ongoing and will evaluate a prototype preclinical transrectal device while optimizing parameters of the BH pulsing scheme. This study was funded by RFBR 17-54-33034, NIH R21CA219793, and EB007643 grants.