Impact of Clot Histological and Physical Properties on Revascularization Strategies in Acute Ischaemic Stroke

项目摘要 这项研究计划的长期目标是改善急性胰腺炎患者的护理， 继发于大血管闭塞缺血性卒中。急性缺血性中风影响多达70万人， 这是美国的第四大死因。约10%的急性缺血性 中风患者表现为大血管闭塞，这与长期发病率高相关 and mortality.截至2015年，机械血栓切除术成为急性缺血性心脏病治疗的标准治疗。 大血管闭塞引起的中风。从那时起，机械设备的使用大大增加。 血栓切除术治疗急性中风 尽管血运重建率很高（约80%），但50%的卒中患者仍存在神经功能不良 结果。此外，20%的患者由于电流的限制而没有成功地实现血运重建。 血运重建技术机械血栓切除术期间的凝块破碎率较高， 大多数患者在缺血区域有残留的微小远端栓塞， 由于凝块回收过程中的碎裂，先前未受影响的血管床中的栓子。高凝块率 碎片和未能清除凝块导致神经系统结局不佳表明，为了 要进一步推进脑卒中干预领域，我们必须将注意力转向血栓科学。 在这个R01计划中，我们将着手进行组织学，物理和成像的全面研究。 急性缺血性卒中血栓的特征，最终目的是研究各种药物的疗效。 不同血凝块表型的血运重建策略，以便急性缺血性卒中患者的护理可以 提高我们提出了一个系统的方法来研究血栓在中风。我们的第一个目标是描述 来自多个国家的大样本急性缺血性卒中患者凝块的组织学特征 机构职能体系然后，将使用该登记研究的数据1）确定凝块表型， 进一步的体外研究和2）确定更常见于血栓的组织学特征， 破碎或难以清除凝块。我们的第二个目标是确定成像生物标志物，以识别困难的 通过对第一个目的中鉴定的凝块表型进行体外成像来检测凝块。我们的第三个目标是 确定在治疗每个凝块时，哪种血运重建技术与上级结局相关 表型这将使用体外流动模型进行，该模型复制了 急性缺血性中风如果成功，这项转化研究计划将直接改善患者的 通过帮助中风社区更好地识别难以治疗的血栓，并提供相关数据， 血管再生技术最适合于易于碎裂或难以去除的凝块。

PROJECT SUMMARY The long-term objective of this research program is to improve the care of patients suffering from acute ischemic stroke secondary to large vessel occlusion. Acute ischemic stroke affects up to 700,000 people a year in the United States and is the fourth leading cause of death. Approximately 10% of acute ischemic stroke patients present with large vessel occlusion which are associated with high rates of long-term morbidity and mortality. As of 2015, mechanical thrombectomy became standard of care for treatment of acute ischemic stroke from large vessel occlusion. Since then, there has been a significant increase in the use of mechanical thrombectomy for acute stroke treatment. Despite high revascularization rates (~80%), 50% of stroke patients still experience poor neurological outcomes. In addition, 20% of patients are not successfully revascularized due to limitations of current revascularization technologies. Rates of clot fragmentation during mechanical thrombectomy are high with most patients having residual tiny distal emboli in the ischemic territory and up to 10% of patients developing emboli in previously unaffected vascular beds due to fragmentation during clot retrieval. High rates of clot fragmentation and failure to remove the clot resulting in poor neurological outcomes suggest that in order to further advance the field of stroke intervention, we must turn our attention to the science of clot. In this R01 program we will embark on a comprehensive study of the histological, physical and imaging characteristics of clot in acute ischemic stroke with the ultimate goal of studying the efficacy of various revascularization strategies on different clot phenoytpes so that care of acute ischemic stroke patients can be improved. We propose a methodical approach to the study of clot in stroke. Our first aim is to characterize the histological characteristics of clots from a large sample of acute ischemic stroke patients from multiple institutions. Data from this registry will then be used to 1) identify clot phenotypes which will be made for further in vitro study and 2) identify histologic characteristics that are more commonly present in clots prone to fragmentation or difficult to remove clots. Our second aim is to identify imaging biomarkers to identify difficult clots by performing in vitro imaging of the clot phenotypes identified in the first aim. Our third aim is to determine which revascularization techniques are associated with superior outcomes when treating each clot phenotype. This will be performed using an in vitro flow model which replicates the physiological conditions of acute ischemic stroke in humans. If successful, this translational research program will directly improve patient outcomes by helping the stroke community better identify difficult to treat clots and provide data on which revascularization techniques are best suited for clots which are prone to fragmentation or difficult to remove.