Abstract

To compare the acute and chronic safety and treatment effects of non-invasive hepatic histotripsy vs. percutaneous microwave (MW) ablation in a healthy porcine model. This was a dual-arm study in which each animal (n = 14) received either a single hepatic microwave (n = 6) or histotripsy (n = 6 single treatment; n = 2 double treatment) under ultrasound guidance. The goal was to create 2.5-3.0 cm short-axis treatments in similar locations across modalities. Animals were survived for 1 month with contrast-enhanced CT imaging on days 0, 2, 7, 14, and 28. On day 28, necropsy and histopathology were performed. All procedures were well-tolerated. MW ablation zones were longer and more oblong, but equivalent in the short axes to histotripsy zones on immediate post-procedure CT (p < 0.001 and p = 0.45, respectively). Overall, MW volumes were larger (21.4 cm3 vs. 13.4 cm3; p = 0.001) and histotripsy treatment zones were more spherical (p = 0.007). Histotripsy zones were close to the prescribed size (p < 0.001). Over the study period, histotripsy treatment zones decreased in volume while microwave ablation zones slightly increased (-83% vs. +17%, p = 0.001). There were several imaging-only findings: Branch portal vein thrombus with both histotripsy (7/8) and MW (6/6), hematoma in 2/6 MW only, and a gallbladder injury in 1/6 MW animals. The ablation zones demonstrated complete cellular destruction for both modalities. Histotripsy was associated with more spherical treatments, fewer biliary complications, and greater treatment zone involution. Hepatic MW and histotripsy treatment in a normal porcine model appear at least equally effective for creating treatment zones with a similar safety profile. • Microwave ablation and histotripsy for liver treatment in a healthy porcine model yield equivalent procedural tolerance and cellular destruction. • Histotripsy was associated with more spherical treatments, fewer biliary complications, and greater treatment zone involution over the 28-day follow-up period. • These findings confirm the safety and efficacy of hepatic histotripsy and support the pursuit of clinical trials to further evaluate the translatability of these results.

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