Predicting Stroke Risk in Intracranial Atherosclerotic Disease with Novel High Resolution,Functional and Molecular MRI Techniques - Resubmission - 1

项目摘要/摘要 这项工作的长期目标是通过识别最脆弱的患者来减少中风的发生 使用核磁共振扫描。目前，大约每8名最初从颅内中风的患者中就有1名 动脉粥样硬化症(ICAD)将在一年内再次中风。可能不能通过医疗检查的患者 管理人员有脑血管储备丧失，侧支动脉供血不足，和/或斑块 易因活跃的巨噬细胞渗入而破裂。我们的目标是识别脆弱的患者，以告知 选择新的医疗管理方案，支架植入或无支架血管成形术。我们将开发一套 新的MRI扫描，并在目标患者群体中进行评估，与参考标准二氧化碳进行比较 挑战CVR、HMPAO SPECT或活性巨噬细胞的直接成像。 重要意义：冠心病是世界范围内导致中风的最常见原因之一，具有极高的风险 反复中风的症状。有严重狭窄(70%至99%)的iCAD患者复发的风险特别高。 尽管接受阿司匹林治疗，但中风的血管区域狭窄(12个月内~12%至20%)， 普立维和危险因素(高血压、吸烟等)的管理。使用新的预防性治疗方法 包括血管成形术在内，如果能识别出最脆弱的患者，新的抗血小板药物将会受益。 我们的成像生物标记物将改善易受攻击的高危人群中风的风险分层 人口。 创新：我们开发了针对ICAD中风风险因素的时间分辨MRI扫描： (1)心脏门控“快照”图像，反映脑血管对动脉反应的瞬时变化 心动周期引起的压力变化。这些变化因脑血管的丧失而减弱。 保留中风的风险事实。 (2)一种新的基于线性时不变系统理论的数学去卷积算法 通过狭窄远端的侧支动脉供血提供给血管床的灌流。 (3)首次应用高分辨率颅内动脉壁通透性检测巨噬细胞的浸润情况。 科学严谨：人类头部的几何形状和血管系统的拓扑结构是独一无二的，因此我们 在预期的患者群体中进行我们的所有研究：患有ICAD的人类。为确保科学严谨，我们将 直接与二氧化碳脑血管储备、侧支动脉供血和 斑块内巨噬细胞浸润。 成功的可能性：我们已经建立了一支强大的、多学科的团队，拥有长期的成功记录， 合作神经血管研究。我们相信成功完成目标和目标的可能性很高 临床翻译的可能性很高。

Project Summary/Abstract The long-term goal of this work is to reduce the incident of stroke by identifying the most vulnerable patients using MRI scans. Currently roughly 1 of every 8 patient who have had an initial stroke from intracranial atherosclerosis disease (ICAD) will suffer a second stroke within a year. Patients who are likely to fail medical management have loss of cerebrovascular reserve, poor collateral arterial blood supply, and/or plaque that is vulnerable to rupture from active macrophage infiltration. Our goal is to identify vulnerable patients to inform the selection for new medical management protocols, stenting or stent-less angioplasty. We will develop a suite of new MRI scans and evaluate them in the intended patient population, comparing to reference standard CO2 Challenge CVR, HMPAO SPECT or direct imaging of active macrophages. Significance: ICAD is one of the most common causes of stroke worldwide and carries an extremely a high risk of recurrent stroke. ICAD patients with severe stenosis (70 to 99%) are at particularly high risk for recurrent stroke in the vascular territory of the stenosis (~12 to 20% within 12 months) despite treatment with aspirin, Plavix and management of risk factors (hypertension, smoking etc). The use of new, preventative treatment including angioplasty, new anti-platelet medication would benefit if the most vulnerable patient can be identified. Our imaging biomarkers will improve risk stratification for the of stroke in a vulnerable, high risk population. Innovation: We have developed time resolve MRI scans that are targeted to risk factor of stroke in ICAD: (1) Cardiac Gated “Snapshot” images of transient changes in the cerebral vasculature in response to arterial pressure changes induced by the cardiac cycle. These changes are muted by a loss of cerebrovascular reserve a risk fact of stroke. (2) A new mathematical deconvolution algorithm based on linear time-invariant system theory to quantify perfusion supplied to a vascular bed through collateral arterial blood supply distal to a stenosis. (3) First ever high-resolution permeability of the intracranial arterial walls to identify macrophage infiltration. Scientific Rigor: The geometry of the human head and topology of the vasculature are unique, and we therefore perform all our studies in the intended patient population: humans with ICAD. To ensure scientific rigor, we will compare directly to reference standard values of CO2 cerebrovascular reserve, collateral arterial supply, and macrophage infiltration in plaques. Probability of Success: We have built a strong, multi-disciplinary team with a long track record of successful, collaborative neurovascular research. We believe this high probability of successful completion of the aims and high likelihood of clinical translation.