IEEE Trans Ultrason Ferroelectr Freq Control. 2021 Sep;68(9):2942-2952. doi: 10.1109/TUFFC.2021.3052393. Epub 2021 Aug 27.
Deep vein thrombosis is a major source of morbidity worldwide. For critical obstructions, catheter-directed thrombolytics are the frontline therapy to achieve vessel recanalization. Techniques that aid lytic therapy are under development to improve treatment efficacy and reduce procedure-related complications. Histotripsy is one such adjuvant under development that relies on focused ultrasound for in situ nucleation of bubble clouds. Prior studies have demonstrated synergistic effects for clot dissolution when histotripsy is combined with lytic therapy. The success of this combination approach is hypothesized to promote thrombolytic efficacy via two mechanisms: erythrocyte fractionation (hemolysis) and increased lytic activity (fibrinolysis). In this study, the contributions of hemolysis and fibrinolysis to clot degradation under histotripsy and a lytic were quantified with measurements of hemoglobin and D-dimer, respectively. A linear regression analysis was used to determine the relationship between hemoglobin, D-dimer, and the overall treatment efficacy (clot mass loss). A similar analysis was conducted to gauge the role of bubble activity, which was assessed with passive cavitation imaging, on hemolysis and fibrinolysis. Tabulation of these data demonstrated hemolysis and fibrinolysis contributed equally to clot mass loss. Furthermore, bubble cloud activity promoted the generation of hemoglobin and D-dimer in equal proportion. These studies indicate a multifactorial process for clot degradation under the action of histotripsy and a lytic therapy.
深静脉血栓形成是全球发病率的主要来源。对于危急的阻塞，导管定向溶栓是实现血管再通的一线治疗方法。正在开发辅助溶栓治疗的技术，以提高治疗效果并减少与手术相关的并发症。Histotripsy 就是正在开发的一种辅助技术，它依赖于聚焦超声实现原位成核泡云。先前的研究表明，当 Histotripsy 与溶栓治疗联合使用时，对于血栓溶解具有协同作用。这种联合方法的成功被假设通过两种机制促进溶栓效果：红细胞分离（溶血）和增加的溶栓活性（纤维蛋白溶解）。在这项研究中，分别通过测量血红蛋白和 D-二聚体来量化 Histotripsy 和溶栓治疗下血栓降解过程中的溶血和纤维蛋白溶解作用。线性回归分析用于确定血红蛋白、D-二聚体和整体治疗效果（血栓质量损失）之间的关系。还进行了类似的分析来评估气泡活动的作用，通过被动声纳成像评估气泡活动对溶血和纤维蛋白溶解的影响。这些数据的列表表明，溶血和纤维蛋白溶解对血栓质量损失的贡献相等。此外，气泡云活动以相等的比例促进血红蛋白和 D-二聚体的生成。这些研究表明，在 Histotripsy 和溶栓治疗的作用下，血栓降解是一个多因素的过程。
