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, forward-viewing 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.

当前微泡（MB）和组织纤溶酶原激活剂（tPA）介导的超声溶栓技术的一大挑战是有效治疗回缩的血凝块，因为回缩的血栓具有高密度和低孔隙率。纳米液滴（ND）由于尺寸小并且能够渗透到回缩的凝块中以增强药物输送，因此具有增强回缩的凝块溶解的潜力。我们首次证明亚兆赫、前视血管内 (FVI) 传感器可用于体外 ND 介导的声溶栓。在这项研究中，我们确定了用低沸点相变纳米液滴和凝块溶解诱导空化的最小峰值负压。然后我们将纳米液滴介导的声溶栓技术与 MB 和 tPA 介导的技术进行比较。对于对照，以回缩凝块质量减少百分比表示的凝块溶解为 9 ± 8%、9 ± 5%、16 ± 5%、14 ± 9%、17 ± 9%、30 ± 8% 和 40 ± 9%分别为单独 tPA 组、tPA + US 组、MB + US 组、MB + tPA + US 组、ND + US 组和 ND + tPA + US 组。在回缩的血栓中，与传统的 MB 和 tPA 介导的超声溶栓技术相比，联合 ND 和 tPA 介导的超声溶栓能够显着增强回缩的血栓溶解。纳米液滴与 tPA 介导的超声溶栓相结合可能为安全治疗回缩的血栓提供可行的策略。