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

颈动脉斑块的 MRI 检测作为不明原因栓塞性中风的机制（MRI DECIPHER）

• 批准号: 10204095
• 负责人: Ajay Gupta
• 金额: $ 82.36万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10204095
• 关键词: Acute; Anatomy; Arterial Fatty Streak; Arteries; Atrial Fibrillation; Blood Vessels; Blood flow; Brain; Brain Infarction; Brain natriuretic peptide; Cardiac; Carotid Arteries; Carotid Artery Plaques; Carotid Endarterectomy; Cerebrovascular Circulation; Clinical; Clinical Trials; Coagulation Process; Contralateral; Data; Detection; Dilatation - action; Disease; Echocardiography; Embolism; Enrollment; Etiology; Evaluation; Event; Face; Fostering; Foundations; Heart Atrium; Hemorrhage; Hospitals; Image; Incidence; Infarction; Inflammation; Inpatients; Internal carotid artery structure; Ipsilateral; Ischemic Stroke; Lead; Left; Link; Magnetic Resonance Imaging; Medical; Mission; Monitor; Multicenter Trials; National Heart, Lung, and Blood Institute; Neurologist; Observational Study; Patients; Physiological; Pilot Projects; Positron-Emission Tomography; Prevention; Preventive therapy; Procedures; Protocols documentation; Public Health; Recurrence; Research; Risk; Risk Factors; Risk Marker; Rupture; Side; Source; Standardization; Stenosis; Stents; Stroke; Stroke prevention; Structure; Suggestion; Testing; Therapeutic; Transcranial Doppler Ultrasonography; Travel; Validation; Vascular Diseases; adjudicate; clinical practice; cryptogenic stroke; embolic stroke; heart rhythm; high risk; imaging detection; imaging study; improved; indexing; insight; novel; personalized medicine; prospective; randomized trial; screening; stroke patient; stroke risk; uptake; vascular risk factor

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.

项目概要/摘要 三分之一的中风无法确定明确的原因。本提案旨在确定是否存在这种情况。 其中一些中风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 目前，只有导致动脉显着狭窄（变窄）的动脉粥样硬化斑块才能被治疗。 然而，试点数据表明，非狭窄斑块——斑块。 未引起动脉狭窄的物质会破裂并产生凝块，凝块向下游流动以阻塞血液 磁共振成像 (MRI) 可以可靠地确定哪些斑块的流量最高。 此类标记物可以识别颈内动脉中的高风险非狭窄斑块。 初步研究表明，对于原因不明的中风患者，大脑的大部分血流是由它们提供的。 发现中风更有可能发生在具有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，发生中风的可能性更大。 高风险非狭窄斑块的下游支持该应用的假设：动脉粥样硬化 即使没有明显的动脉狭窄，脑循环中的斑块也与中风相关。 这种非狭窄斑块可以解释相当大比例的中风，其原因目前看来 先前的临床试验发现，更好地识别这些斑块可能会导致更好的中风预防。 颈动脉内膜切除术/支架置入术对于预防患有以下疾病的患者中风复发无效： 非狭窄斑块，这种斑块现在在临床实践中被忽视，但是，还没有试验进行过测试。 仅针对非狭窄斑块导致中风的中风患者进行颈动脉内膜切除术/支架置入术 复发风险足够高，以至于该手术的好处大于其风险。 本申请中提出的将确定一种新的中风危险因素，并为中风建立科学前提 该应用程序针对 200 名患者进行前瞻性观察研究。 不明原因中风的患者将使用详细的 MRI 方案来检测斑块内出血， 还将对 150 名受试者进行 PET/MRI 研究。 对斑块炎症等高风险特征的进一步深入了解将检验大脑的假设。 高风险非狭窄斑块一侧的梗塞比目标 2 的另一侧更常见。 检验这样的假设：深入的中风评估很少会在受试者中发现替代解释 目标 3 将检验以下假设： 与高危非狭窄斑块同侧相比，复发性梗塞更常发生在非狭窄斑块的同一侧。 这些假设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非狭窄斑块患者的动脉内膜切除术/支架置入术。