Cavitation dynamics of histotripsy bubble cloud nucleated from echogenic liposomes

Abstract

Deep vein thrombosis is a serious health concern worldwide. Administration of catheter-directed thrombolytics is the primary approach to achieve vessel patency for critical obstructions. Adjuvant techniques that localize thrombolytic delivery will improve treatment outcomes and reduce the potential caustic bleeding associated with systemic lytic administration. Histotripsy is a bubble-based focused ultrasound therapy that has been shown to act synergistically with lytic to promote clot degradation. Combining histotripsy with a targeted drug delivery agent may further improve treatment efficacy. Echogenic liposomes are vesicles formulated to entrain the thrombolytic, and can be triggered with ultrasound to release drugs locally. The objective of this study was to assess histotripsy bubble cloud dynamics nucleated from echogenic liposomes in an in vitro venous flow model. The change in liposome echogenicity following histotripsy exposure was assessed with high frame rate imaging. Hypoechogenicity indicative of liposome destruction extended beyond the focal region, with a strong decrease in pixel intensity immediately after the applied histotripsy pulse. Interestingly, echogenicity was restored to baseline levels over the course of ∼4 s, which was attributed to vigorous fluid mixing from bubble cloud oscillations. These results indicate an interesting range of bubble cloud behaviors when histotripsy is combined with echogenic liposomes.