Non-Invasive Ultrasound Liver Ablation Using Histotripsy: Chronic Study in an In Vivo Rodent Model

Abstract Hepatocellular carcinoma, or liver cancer, has the fastest growing incidence among cancers in the United States. Current liver ablation methods are thermal-based and share limitations due to the heat sink effect from the blood flow through the highly vascular liver. Recently, our group has investigated histotripsyas a non-invasive liver cancer ablation method. Histotripsyis a non-thermal ultrasonic ablation method that fractionates tissue through the control of acoustic cavitation. Previous experiments in an in vivo porcine model show that histotripsycan create well-confined lesions in the liver through ribcage obstruction without damaging the overlying ribs and other tissues. Histotripsycan also completely fractionate liver tissue surrounding major vessels while preserving the vessels. In this study, we investigate the long-term effects of histotripsyliver ablation in a rodent model. We hypothesize that the fractionated histotripsylesion will be resorbed by the liver, resulting in effective tissue healing. To test this hypothesis, the livers of 20 healthy rats were treated with histotripsyusing an 8-element 1-MHz histotripsytransducer. Rats were euthanized after 0, 3, 7, 14 and 28 days (n = 4). In vivo and post mortem results showed histotripsylesions were successfully generated through the intact abdomen in all 20 rats. Magnetic resonance imaging found primarily negative contrast on day 0, positive contrast on day 3 and rapid normalization of signal intensity thereafter ( i.e., signal amplitude returned to baseline levels seen in healthy liver tissue). Histologically, lesions were completely fractionated into an acellular homogenate. The lesions had a maximum cross-sectional area of 17.2 ± 1.9 mm 2 and sharp boundaries between the lesion and the healthy surrounding tissue after treatment. As the animals recovered after treatment, the histotripsytissue homogenate was almost completely replaced by regenerated liver parenchyma, resulting in a small fibrous lesion ( 2 maximum cross-section) remaining after 28 d. The results of this study suggest that histotripsyhas potential as a non-invasive liver ablation method for effective tissue removal.