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

项目概要/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名患者中就有1名患有颅内动脉瘤的初次卒中。 动脉粥样硬化性疾病（ICAD）患者将在一年内遭受第二次中风。有可能在医疗过程中失败的患者 管理有脑血管储备损失，不良侧支动脉血液供应，和/或斑块， 容易因活跃的巨噬细胞浸润而破裂。我们的目标是确定脆弱的病人， 选择新的医疗管理方案，支架或无支架血管成形术。我们将开发一套 新的MRI扫描，并在预期患者人群中对其进行评价，与参考标准CO2进行比较 激发CVR、HMPAO SPECT或活性巨噬细胞的直接成像。 重要性：ICAD是全球中风最常见的原因之一，具有极高的风险 复发性中风严重狭窄（70 - 99%）的ICAD患者复发的风险特别高， 尽管接受了阿司匹林治疗，狭窄血管区域仍发生卒中（12个月内约12 - 20%）， 血小板减少和风险因素管理（高血压、吸烟等）。使用新的预防性治疗 包括血管成形术，如果能够确定最脆弱的病人，新的抗血小板药物将受益。 我们的影像学生物标志物将改善脆弱、高危人群中卒中的风险分层， 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，显示脑血管系统对动脉 由心动周期引起的压力变化。这些变化被脑血管的损失所掩盖 保留中风的危险因素。 (2)基于线性时不变系统理论量化的新数学反卷积算法 通过狭窄远端的侧支动脉血液供应提供给血管床的灌注。 (3)首次通过颅内动脉壁的高分辨率渗透性来识别巨噬细胞浸润。 科学严谨性：人类头部的几何形状和脉管系统的拓扑结构是独特的，因此， 在预期患者人群中进行我们的所有研究：患有ICAD的人类。为了确保科学严谨，我们将 直接与CO2脑血管储备、侧支动脉供应的参考标准值进行比较， 斑块中巨噬细胞浸润。 成功的可能性：我们已经建立了一个强大的，多学科的团队，具有长期的成功记录， 神经血管合作研究我们认为，成功完成目标的可能性很高， 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.