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

项目摘要/摘要 在三分之一的中风中，无法确定确切的原因。这项提案旨在确定 这些中风中的一些实际上是由于动脉中未被识别的动脉粥样硬化斑块导致的 大脑。目前，只有导致动脉显著狭窄(狭窄)的动脉粥样硬化斑块才能 被视为中风的根本原因。然而，试点数据表明，非狭窄斑块-斑块 不会导致动脉狭窄--可以破裂并产生血栓，向下游流动以阻塞血液 流向大脑。磁共振成像(MRI)可以可靠地确定哪些斑块最高 有破裂的危险。这些标记物可以识别颈内动脉中的高危非狭窄斑块， 为大脑提供大部分的血液流动。在一名原因不明的中风患者中，初步研究表明 发现中风更有可能发生在颈动脉无狭窄的高危一侧 而不是在没有高危斑块的对侧。中风的发生趋势 高危非狭窄斑块的下游支持这一应用的假说：动脉粥样硬化 即使在没有明显动脉狭窄的情况下，脑循环中的斑块也与中风有关。 这种非狭窄斑块可以解释相当大比例的中风，目前其原因似乎是 未知。更好地识别这些斑块可能会导致更好的中风预防。先前的临床试验发现 颈动脉内膜剥脱术/支架置入术对预防中风复发无效 非狭窄斑块，这种斑块在临床上现在被忽视了。然而，还没有试验测试过 颈动脉内膜剥脱术/支架植入术仅适用于非狭窄斑块导致中风的中风患者 复发的风险足够高，以至于手术的好处超过了风险。如果成功，这项研究 在本申请中提出的将确定新的中风风险因素并为 潜在的变革性治疗策略。这项申请是针对200人的前瞻性观测研究。 原因不明的中风患者。一个详细的磁共振成像方案将被用来检测斑块内出血， 高危无狭窄斑块的标志物。在150名受试者中，还将进行PET/MRI研究 对斑块炎症等高危特征的更多洞察。目标1将测试大脑的假设 高危非狭窄斑块一侧的梗塞比对侧更常见。目标2将 测试一种假设，即深入的中风评估不会经常在受试者中发现另一种解释 有高危无狭窄斑块的患者明显多于无此类斑块的患者。目标3将检验这一假设 与高危非狭窄斑块同侧相比，复发性脑梗塞更容易发生。 另一边。这些假说的验证将为颈动脉的多中心随机试验奠定基础 隐源性卒中和同侧高危无狭窄斑块患者的动脉内膜切除术/支架置入术。

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.