A Model of High-Speed Endovascular Sonothrombolysis with Vortex Ultrasound-Induced Shear Stress to Treat Cerebral Venous Sinus Thrombosis

This research aims to demonstrate a novel vortex ultrasound enabled endovascular thrombolysis method designed for treating cerebral venous sinus thrombosis(CVST).This is a topic of substantial importance since current treatment modalities for CVST still fail in as many as 20%to 40%of the cases,and the incidence of CvST has increased since the outbreak of the coronavirus disease 2019 pandemic.Compared with conventional anticoagulant or thrombolytic drugs,sonothrombolysis has the potential to remarkably shorten the required treatment time owing to the direct clot targeting with acoustic waves.However,previously reported strategies for sonothrombolysis have not demonstrated clinically meaningful outcomes(e.g.,recanalization within 30 min)in treating large,completely occluded veins or arteries.Here,we demonstrated a new vortex ultrasound technique for endovascular sonothrombolysis utilizing wavematter interaction-induced shear stress to enhance the lytic rate substantially.Our in vitro experiment showed that the lytic rate was increased by at least 64.3%compared with the nonvortex endovascular ultrasound treatment.A 3.1-g,7.5-cm-long,completely occluded in vitro 3-dimensional model of acute CVST was fully recanalized within 8 min with a record-high lytic rate of 237.5 mg/min for acute bovine clot invitro.Furthermore,we confirmed that the vortex ultrasound causes no vessel wall damage over ex vivo canine veins.This vortex ultrasound thrombolysis technique potentially presents a new life-saving tool for severe CVST cases that cannot be efficaciously treated using existing therapies.

Nanodroplet-mediated catheter-directed sonothrombolysis of retracted blood clots

One major challenge in current microbubble(MB)and tissue plasminogen activator(tPA)-mediated sonothrombolysis techniques is effectively treating retracted blood clots,owing to the high density and low porosity of retracted clots.Nanodroplets(NDs)have the potential to enhance retracted clot lysis owing to their small size and ability to penetrate into retracted clots to enhance drug delivery.For the first time,we demonstrate that a sub-megahertz,forwardviewing intravascular(FVI)transducer can be used for ND-mediated sonothrombolysis,in vitro.In this study,we determined the minimum peak negative pressure to induce cavitation with low-boiling point phase change nanodroplets and clot lysis.We then compared nanodroplet mediated sonothrombolysis to MB and tPA mediate techniques.The clot lysis as a percent mass decrease in retracted clots was 9±8%,9±5%,16±5%,14±9%,17±9%,30±8%,and 40±9%for the control group,tPA alone,tPA+US,MB+US,MB+tPA+US,ND+US,and ND+tPA+US groups,respectively.In retracted blood clots,combined ND-and tPA-mediated sonothrombolysis was able to significantly enhance retracted clot lysis compared with traditional MB and tPA-mediated sonothrombolysis techniques.Combined nanodroplet with tPA-mediated sonothrombolysis may provide a feasible strategy for safely treating retracted clots.