ИСТИНА

Background: Histotripsy ablation of the prostate may offer benefits over thermal High Intensity Focused Ultrasound (HIFU) due to its precise non-thermal mechanism and real-time visualization using B-mode ultrasound (US). Prior studies have evaluated transabdominal and transperineal shock scattering cavitation histotripsy, based on using microsecond-long pulses, for treating benign prostatic hyperplasia and prostate cancer. Our group has been developing a transrectal boiling histotripsy (BH) method, which uses sequences of millisecond-long pulses with shock fronts to produce vapor bubbles at the focus. Interaction between the vapor bubbles and ensuing shocks produces non-thermal mechanical tissue ablation. In this study, we assessed the feasibility of BH ablation of the prostate using a prototype transrectal device. Materials and Methods: A custom-built transrectal BH system comprising a 2 MHz HIFU transducer (5.0 x 3.5 cm, focal length 4.0 cm) with in-line B-mode imaging (BK 3000, probe E14C4) (Fig. 1) mounted onto an automated translation/rotation stage. To confirm prostate BH pulse parameters, fresh ex vivo prostate tissue specimens were collected (N = 3 canines and N = 3 humans (IRB approved procurement protocol)), embedded in degassed 1.5% agarose gel and then treated with BH. Following tissue experiments, in vivo transrectal BH was assessed in N = 6 anesthetized canine subjects. Immediately following BH treatment, the subjects were euthanized and the prostate was harvested. During the treatment, input power was titrated up to establish the threshold for vapor bubble formation as seen with B-mode ultrasound imaging. BH pulses were 10 ms duration with pulse repetition frequency of 1 Hz. Single-foci and volumetric lesions were created by mechanically translating the focus through the tissue with 1 mm increments. A total of 10-60 BH pulses per focus were administered. Specimens were formalin-fixed and evaluated histologically. Results: BH tissue liquefaction was feasible in all ex vivo tissues and in vivo experiments. The bubble threshold was similar in ex vivo canine and human tissue corresponding to a shock amplitude of 58-68 MPa at the focus. BH produced discrete lesions of mechanically disintegrated tissue in both canine and human tissue, however, human tissue was more resistant to BH, requiring more pulses to achieve similar degrees of disintegration. (Fig. 2) In vivo, the threshold for BH vapor bubble initiation was greater corresponding to at least 88 MPa shock amplitude. On B-mode, BH produced well defined hypoechoic lesions that corresponded well with gross and histologic findings (Fig. 3). On histology, well-defined lesions were observed containing homogenized tissue debris with areas of erythrocytes. At necropsy, no evidence of collateral injury was observed. Conclusions: Transrectal BH ablation of the prostate is feasible using a preclinical prototype BH system. Further ex vivo and in vivo studies are needed to characterize the impact of tissue properties and surrounding anatomic structures on histotripsy parameters and optimize future clinical implementations. Acknowledgements: Funding: NIH R01EB007643, R21CA219793, R01DK119310, and RFBR 175433034.