Histotripsy Thrombolysis on Retracted Clots

Abstract

Retracted blood clots have been previously recognized to be more resistant to drug-based thrombolysis methods, even with ultrasound and microbubble enhancements. Microtripsy, a new histotripsy approach, has been investigated as a non-invasive, drug-free and image-guided method that uses ultrasound to break up clots with improved treatment accuracy and a lower risk of vessel damage compared with the traditional histotripsy thrombolysis approach. Unlike drug-mediated thrombolysis, which is dependent on the permeation of the thrombolytic agents into the clot, microtripsy controls acoustic cavitation to fractionate clots. We hypothesize that microtripsy thrombolysis is effective on retracted clots and that the treatment efficacy can be enhanced using strategies incorporating electronic focal steering. To test our hypothesis, retracted clots were prepared in vitro and the mechanical properties were quantitatively characterized. Microtripsy thrombolysis was applied on the retracted clots in an in vitro flow model using three different strategies: single-focus, electronically-steered multi-focus and dual-pass multi-focus. Results show that microtripsy was used to successfully generate a flow channel through the retracted clot and the flow was restored. The multi-focus and the dual-pass treatments incorporating the electronic focal steering significantly increased the recanalized flow channel size compared to the single-focus treatments. The dual-pass treatments achieved a restored flow rate up to 324 mL/min without cavitation contacting the vessel wall. The clot debris particles generated from microtripsy thrombolysis remained within the safe range. The results of this study show the potential of microtripsy thrombolysis for retracted clot recanalization with the enhancement of electronic focal steering.

Keywords: Histotripsy; Retracted clot; Sonothrombolysis; Thrombolysis; Tissue elasticity.