Mechanical disintegration of benign and malignant tumors in ex vivo human prostate tissues using boiling histotripsy

The feasibility of boiling histotripsy (BH) to mechanically liquefy ex vivo human prostate tissue with benign hyperplasia (BPH) and adenocarcinoma (PCa) was assessed. Volumetric BH lesions were generated in fresh tissue samples under B-mode guidance using a 1.5-MHz focused transducer, 10- and 1-ms pulses with 1% duty cycle. Prior to BH exposures, the samples were analyzed using shear wave elastography (SWE) to determine whether their mechanical properties were clinically representative. Completeness and efficiency of ablation for BH lesions were evaluated grossly, histologically, and using B-mode ultrasound. The SWE measured Young’s modulus of the samples was shown to be within the typical range observed clinically. During the exposures, BH-induced hyperechogenic bubbles were visible using B-mode, and post-treatment hypoechoic regions indicated successful tissue fractionation. Gross analysis of the exposed samples with BPH revealed ablation of the targeted tissue inside stiff BPH nodules. The sonications using 1-ms pulses (with 150 pulses-per-focus) were twofold faster comparing to 10-ms (with 30 pulses-per-focus). Histological analysis revealed liquefied lesions containing homogenized cell debris in all BPH samples. A pilot experiment of human PCa tumor fractionation into subcellular fragments was confirmed histologically. [Work supported by R01CA258581, R01DK119310, and RSF 20-12-00145.]