Hepatic Histotripsy after Contrast-Enhanced Ultrasound: Evaluation of Safety and Efficacy in an In Vivo Swine Model

PURPOSE: To assess the safety and efficacy of performing histotripsy after ultrasound (US) contrast administration, which potentially lowers cavitation threshold in tissue. MATERIALS AND METHODS: Six healthy female swine (mean age, 14.25 weeks; weight, 52.3 kg) each underwent 2 histotripsy treatments (2.0 cm) of the liver, 1 before US contrast (2.4 mL, Lumason) administration (control) and the other 10 minutes after contrast administration (post-contrast-enhanced US [CEUS]). US (intraprocedural B-mode and posttreatment CEUS), magnetic resonance (MR) imaging, and gross necropsy were used to assess off-target damage to determine safety. Efficacy was assessed by comparing planned and actual treatment zone dimensions on posttreatment MR imaging and by confirming histologic cell death. Data were analyzed using a paired, 1-sided t-test (α = 0.05) and Bland-Altman analysis. RESULTS: All 12 treatments were well demarcated and visible on posttreatment CEUS and MR imaging. No off-target damage was noted during treatment or necropsy. One post-CEUS treatment was associated with mild T2 hyperintensity in the abdominal wall adjacent to the treatment zone without an identifiable pathologic correlate. Secondary and tertiary portal or hepatic thromboses were observed in 5 of 6 post-CEUS treatments and all 6 control treatments. No significant difference in mean diameter was observed between control and post-CEUS treatments (P = .31, P = .79, and P = .96, for anteroposterior, transverse, and craniocaudal dimensions, respectively). Bland-Altman analysis showed a bias of ≤2 mm across all dimensions. Complete cellular destruction was observed within all histotripsy treatment zones, regardless of exposure to US contrast before treatment. CONCLUSIONS: In this in vivo swine model, hepatic histotripsy after contrast-enhanced US was as safe and effective as treatment without any prior US contrast.