Assessment of histotripsy and thrombolytic in a porcine model of venous thrombosis

Abstract

Deep vein thrombosis (DVT) is a significant source of morbidity and mortality worldwide. Catheter-directed thrombolytics are the standard-of-care treatment for critical obstructions, but have limitations that motivate the development of adjuvant strategies. Histotripsy is a focused ultrasound therapy that generates spontaneous bubbles in tissue at depth. In vitro studies have demonstrated histotripsy enhances the action of thrombolytic drugs to promote robust clot degradation. The goal of this study was to assess outcomes for this combination therapy in a porcine model of DVT. Thrombi were formed in the femoral vein were exposed to thrombolytic drug using a multi-side port infusion catheter. During the infusion, histotripsy bubble activity was generated using a focused transducer designed specifically for iliofemoral targets. A venous filter was placed in the inferior vena cava to capture treatment-induced emboli. Fluoroscopy and ultrasound imaging were used to assess outcomes for thrombi exposed to thrombolytic drugs with or without histotripsy. For thrombi exposed to thrombolytic alone, partial flow was observed in one of four cases on Doppler ultrasound. Thrombolytic alone resulted in no apparent changes in the thrombus burden on B-mode ultrasound or contrast perfusion on fluoroscopy. For histotripsy and thrombolytic, flow was increased on Doppler for 8 of 9 cases, and the thrombus burden was reduced ~ 55%. Semi-quantitative markers of fluoroscopy indicated strong perfusion within targeted regions. Further, no emboli were found in venous filters. Overall, these ongoing studies suggest histotripsy combined with catheter-directed thrombolytic is a promising approach to treat venous clots.