MRI Detection of CarotId Plaques as a mecHanism for Embolic strokes of undeteRmined source (MRI DECIPHER)

项目总结/摘要 在三分之一的中风中，无法确定确切的原因。该提案旨在确定， 事实上，这些中风中的一些是由动脉中未被识别的动脉粥样硬化斑块引起的， 个脑袋目前，只有导致动脉显著狭窄（变窄）的动脉粥样硬化斑块才被治疗。 被当作中风的根本原因然而，试验数据表明，非狭窄斑块-斑块 没有引起动脉狭窄的血管会破裂并产生血栓，血栓会向下游流动，阻塞血液 流向大脑。磁共振成像（MRI）可以可靠地确定哪些斑块具有最高的 破裂的风险。这些标记物可以识别颈内动脉中的高危非狭窄斑块， 供应大脑的大部分血液在不明原因的中风患者中，初步研究 发现中风更有可能发生在高风险非狭窄的颈动脉一侧 与不存在高风险斑块的对侧相比，中风发生的趋势 高风险非狭窄斑块的下游支持本申请的假设：动脉粥样硬化 脑循环中的斑块与中风相关，即使没有显著的动脉狭窄。 这种非狭窄斑块可以解释相当大比例的中风，目前看来， 未知更好地识别这些斑块可能会导致更好的中风预防。之前的临床试验发现 颈动脉内膜切除术/支架植入术对于预防中风复发无效， 非狭窄斑块，并且这种斑块现在在临床实践中被忽视。然而，没有一项试验 颈动脉内膜切除术/支架植入术仅用于非狭窄斑块导致卒中的卒中患者 复发风险足够高，以至于手术的受益超过其风险。如果成功，研究 本申请中提出的方法将确定一种新的中风危险因素，并为预防中风建立科学前提。 潜在的变革性治疗策略。本申请是一项前瞻性观察性研究， 不明原因中风的患者。详细的MRI方案将用于检测斑块内出血， 高风险非狭窄斑块的标志物。在150例受试者中，还将进行PET/MRI研究， 对斑块炎症等高风险特征的进一步了解。目标1将检验大脑 梗死在高风险非狭窄斑块一侧比相对侧更常见。目标2将 检验以下假设：深入的卒中评估将较少发现受试者的其他解释 高风险的非狭窄性斑块比那些没有这种斑块。目标3将检验以下假设： 与高风险非狭窄斑块相比， 对面。这些假设的验证将为颈动脉粥样硬化的多中心随机试验奠定基础。 隐源性卒中和同侧高危非狭窄斑块患者的动脉内膜切除术/支架植入术。

PROJECT SUMMARY/ABSTRACT In one-third of strokes, a definite cause cannot be established. This proposal seeks to determine if some of these strokes in fact resulted from unrecognized atherosclerotic plaque in the arteries leading to the brain. Currently, only atherosclerotic plaques that cause significant stenosis (narrowing) of an artery are treated as the underlying cause of a stroke. However, pilot data suggest that nonstenosing plaques—plaques that have not caused arterial narrowing—can rupture and produce clots that travel downstream to block blood flow to the brain. Magnetic resonance imaging (MRI) can reliably determine which plaques have the highest risk of rupture. Such markers can identify high-risk nonstenosing plaques in the internal carotid arteries, which supply the majority of the brain's blood flow. In a patient with a stroke of unknown cause, pilot studies have found that the stroke is more likely to have occurred on the side of a carotid artery with high-risk nonstenosing plaque than on the opposite side where no high-risk plaque is present. The tendency of strokes to occur downstream of a high-risk nonstenosing plaque supports this application's hypothesis: that atherosclerotic plaque in the cerebral circulation is associated with stroke even in the absence of significant arterial narrowing. Such nonstenosing plaques may explain a substantial proportion of strokes whose cause currently seems unknown. Better recognition of these plaques may lead to better stroke prevention. Prior clinical trials found that carotid endarterectomy/stenting was not effective for preventing stroke recurrence in patients with nonstenosing plaque, and such plaques are now ignored in clinical practice. However, no trial has tested carotid endarterectomy/stenting in only those stroke patients whose nonstenosing plaque entails a stroke recurrence risk high enough that the benefits of the procedure outweigh its risks. If successful, the research proposed in this application would identify a novel stroke risk factor and establish the scientific premise for a potentially transformative therapeutic strategy. This application is for a prospective observational study of 200 patients with stroke of unknown cause. A detailed MRI protocol will be used to detect intraplaque hemorrhage, a marker of high-risk nonstenosing plaque. In 150 of the subjects, a PET/MRI study will also be performed for additional insight into high-risk features such as plaque inflammation. Aim 1 will test the hypothesis that brain infarcts will be more common on the side of a high-risk nonstenosing plaque than the opposite side. Aim 2 will test the hypothesis that in-depth stroke evaluation will less often uncover an alternative explanation in subjects with high-risk nonstenosing plaque than in those without such plaques. Aim 3 will test the hypothesis that recurrent infarction will occur more often on the same side as high-risk nonstenosing plaque than on the opposite side. Validation of these hypotheses would set the stage for a multicenter, randomized trial of carotid endarterectomy/stenting in patients with cryptogenic stroke and ipsilateral high-risk nonstenosing plaque.