Ultrasound and Intra-Clot Microbubbles Enhanced Catheter-Directed Thrombolysis in Vitro and in Vivo

Insufficient penetration of microbubbles (MBs) into the vessel-obstructing thrombi significantly reduces the effectiveness of ultrasound thrombolysis (UT). The widely performed catheter-directed therapy (CDT) makes it possible to increase the local concentration of MBs in the clot. In an occluded vessel with a bypass, treatment of fresh human whole blood clots with CDT-based UT (intra-clot injection of MBs and urokinase, with ultrasound exposure) resulted in a significantly higher percentage of weight loss (35.32 ± 15.42%), compared with CDT alone (19.64 ± 4.71%), non-CDT-based UT (systemic administration of urokinase and MBs, with ultrasound exposure, 8.79 ± 3.02%) and systemic thrombolysis (7.90 ± 2.14). Ultrasound and intra-clot MB enhancement of CDT was further confirmed by a rabbit IVC thrombolysis study, where CDT-based UT resulted in significantly more effective thrombolysis compared with CDT alone. In summary, combining CDT with intra-clot MB-induced acoustic cavitation can improve thrombolysis.