稳定动脉易损斑块具有重要的临床价值，然而，目前其治疗手段具有一定的局限性。研究显示：斑块内聚集的活化血小板或富血小板血栓与易损性显著相关，表明斑块内活化血小板可作为治疗易损斑块的靶点，然而抗血小板药物的治疗缺乏局部靶向性，其出血风险及药物抵抗现象限制了其临床应用。超声联合微泡可以通过对血管壁产生直接和局部的物理损伤效应，溶解大血管急性富血小板血栓，而且我们前期研究已证实诊断超声联合环RGD微泡能靶向显影易损斑块上的活化血小板。因此，我们提出假设：诊断超声联合环RGD微泡能靶向消溶斑块内的活化血小板从而改善斑块易损性。本项目拟采用超声分子成像、组织病理和电镜等方法，在小鼠动脉粥样模型上，A、验证斑块内活化血小板与其易损性相关；B、探索靶向消溶斑块内活化血小板的适宜超声条件；C、评价超声联合MBcRGD治疗易损斑块的有效性和可行性及其病理机制，以期发展出一种有效、安全的治疗易损斑块的新方法。

Stabilization of atherosclerotic plaques has great important clinical implications for preventing future cardiovascular events. Unfortunately, current methods for stabling vulnerable plaques are limited. Accumulated evidence has shown that activated platelet/platelet-rich thrombus in plaques which were significantly related to plaque vulnerability, maybe can serve as a novel target for the treatment of vulnerable plaques. However, systemic anti-platelet agents without plaque-targeting have shown limited success in clinical practice because of bleed risk and drug resistance. Ultrasound combined with microbubble can dissolve the acute platelet-rich thrombus in large vascular through its direct and localized mechanical damage on vessel walls. In additation, our previous studies have demonstrated that low-intensity diagnostic ultrasound combined with MB-cRGD (DU+MB-cRGD) can targeted imaging the activated platelets in the plaques. Therefore, we hypothesized that low-intensity DU+MB-cRGD is capable to targeted dissolve the activated platelets/platelet-rich thrombi in plaque and consequently improve the vulnerability of plaque. This project is proposed to: (1) verify the correlation between the activated platelet in the plaque and its vulnerability; (2) explore the appropriate ultrasound condition for targeted dissolving the activated platelet in the plaque; (3) evaluate the effect of DU+MB-cRGD on treatment of vulnerable plaques and its pathological mechanism by ultrasound molecular imaging, histological examinations, scanning/transimission electron microscopy test, so as to develop an efficient and safe approach for the treatment of vulnerable plaques.