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

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.