BACKGROUND Vascular thrombosis can be treated pharmacologically, however, serious shortcomings such as bleeding may occur. Several studies suggest that sonothrombolysis can induce lysis of the clots using ultrasound. Moreover, intravenously injected thin-shelled microbubbles (MBs) combined with ultrasound can further improve clot lysis. Thick-shelled MBs have been used for drug delivery, targeting and multimodal imaging. However, their capability to enhance sonothrombolysis is unknown. In this study, using an in-vitro set-up, the enhancement of clot lysis using ultrasound and thick-shelled MBs was investigated. Thin-shelled MBs was used for comparison. METHOD The main components in the in-vitro set-up was a vessel mimicking phantom, a pressure mearing system and programmable ultrasound machine. Blood clots were injected and entrapped on a pore mesh in the vessel phantom. Four different protocols for ultrasound transmission and MB exposure (7 blood clots/protocol) were considered together with a control test were no MBs and ultrasound were used. For each protocol, ultrasound exposure of 20 min was used. The upstream pressure of the partially occluded mesh was continuously measured to assess clot burden. At the end of each protocol blood clots were removed from the phantom and the clot mass loss was computed. RESULTS For the thick-shelled MBs no difference in clot mass loss compared with the control tests was found. A 10% increase in the clot mass loss compared with the control tests was found when using thin-shelled MBs and low pressure/long pulses ultrasound exposure. Similarly, in terms of upstream pressure over exposure time, no differences were found when using the thick-shelled MBs, whereas thin-shelled MBs showed a 15% decrease achieved within the first 4 min of ultrasound exposure. CONCLUSION No increase in clot lysis was achieved using thick-shelled MBs as demonstrated by no significant change in clot mass or upstream pressure. Although thick-shelled MBs are promising for targeting and drug delivery, they do not enhance clot lysis when considering the ultrasound sequences used in this study. On the other hand, ultrasound in combination with thin-shelled MBs can facilitate thrombolysis when applying long ultrasound pulses with low pressure.

中文翻译：

---

使用厚壳聚合物微泡的体外声溶栓 - 与薄壳微泡的比较。


背景技术血管血栓形成可以通过药物治疗，然而，可能会出现出血等严重缺点。多项研究表明，超声溶栓可以利用超声波诱导血栓溶解。此外，静脉注射薄壳微泡（MB）结合超声可以进一步改善血栓溶解。厚壳MB已用于药物输送、靶向和多模态成像。然而，它们增强超声溶栓的能力尚不清楚。在这项研究中，使用体外装置，研究了使用超声波和厚壳 MB 增强血栓溶解的效果。使用薄壳MB进行比较。方法 体外装置的主要组件是模拟血管模型、压力测量系统和可编程超声机。血凝块被注射并截留在血管模型中的孔网上。考虑了四种不同的超声传输和 MB 暴露方案（7 个血块/方案）以及没有 MB 且使用超声的对照测试。对于每个方案，使用 20 分钟的超声暴露。连续测量部分闭塞网的上游压力以评估血栓负荷。在每个方案结束时，从体模中去除血块并计算血块质量损失。结果 与对照测试相比，厚壳 MB 的凝块质量损失没有发现差异。当使用薄壳 MB 和低压/长脉冲超声暴露时，发现与对照测试相比，凝块质量损失增加了 10%。 同样，就暴露时间的上游压力而言，使用厚壳 MB 时没有发现差异，而薄壳 MB 在超声波暴露的前 4 分钟内显示出 15% 的降低。结论 使用厚壳 MB 并没有增加凝块溶解，凝块质量或上游压力没有显着变化就证明了这一点。尽管厚壳 MB 有希望用于靶向和药物输送，但考虑到本研究中使用的超声序列，它们并不能增强血栓溶解。另一方面，超声波与薄壳 MB 相结合，在施加低压长超声波脉冲时可以促进血栓溶解。