Non-invasive Ultrasound Liver Ablation Using Histotripsy: A Feasibility Study in Ex Vivo Porcine Liver and a Chronic Study in Rodent Models In Vivo.

Abstract

Objective: This study aimed to investigate the feasibility of histotripsy ablating the liver ex vivo, as well as characterize the acute and chronic impact of histotripsy in vivo.

Methods: A home-made histotripsy system was used to treat liver tissues. A 42-element near-half spherical focusing transducer array was designed with a 13.5 cm focal length, 24 cm aperture and 710 kHz frequency, with an f-number of 0.2083. Initial parameter exploration was measured. The type of histotripsy used lies between the intrinsic threshold cavitation and shock-scattering histotripsy with a pulse duration of 1-3 μs, pulse repetition frequency range of 166-250 Hz and pressure of >50 MPa. Acute and chronic observational experiments were utilized in rodent models in vivo to assess the efficacy and safety of histotripsy, with endpoints at 0, 3, 7, 14 and 28 d post-ablation. Ablation was characterized using hematoxylin-eosin staining, with Masson's trichrome staining conducted to visualize the deposition and distribution of collagen fibers, and TdT-mediated dUTP nick-end labeling (TUNEL) assay used to reveal the spatiotemporal evolution of apoptosis. α-SMA and TGF-β expression was detected to track the process of fibrosis activation and regression in vivo. Serum alanine aminotransferase and aspartate aminotransferase were detected to examine liver function.

Results: The XC-100 histotripsy system developed by the study was able to achieve complete mechanical ablation of both ex vivo and in vivo liver tissues without inducing thermal damage. Unlike high-intensity focused ultrasound, the liver tissue in the targeted area post-histotripsy demonstrated the ability to repair and regenerate, thereby ensuring safety and reliability.

Conclusion: This study provides further evidence for the effectiveness and safety of histotripsy.