AbstractPurpose Contrast-enhanced ultrasound(CEUS) is commonly used to increase the conspicuity of liver tumors. However, the safety and efficacy of performing histotripsy after ultrasound contrast administration, which potentially lowers the cavitation threshold of the tissue, is unknown. Materials and Methods Six healthy female swine (mean age/weight:14.25wk/52.3kg) each underwent two histotripsy treatments (2.0cm) of the liver, one before ultrasound contrast (2.4 mL,Lumason) administration (control) and one 10 minutes after (post-CEUS). Ultrasound (intraprocedural B-mode and post-treatment CEUS), MRI 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 post-treatment MRI and by confirming histologic cell death. Data were analyzed using a paired, one-sided t-test(α=0.05) and Bland-Altman analysis. Results 12/12 treatments were well demarcated and visible on post-treatment CEUS and MRI. 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 5/6 post-CEUS and 6/6 control treatments. No significant difference in mean diameter was observed between control and post-CEUS treatments(p=0.31,0.79,0.96, for anteroposterior, transverse, and craniocaudal dimensions). 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 ultrasound contrast before treatment. Conclusion In this in vivo swine model, hepatic histotripsy after CEUS was as safe and effective as treatment without any prior ultrasound contrast.
Falk et al. (Sun,) studied this question.