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

利用新型高分辨率、功能性和分子 MRI 技术预测颅内动脉粥样硬化疾病的中风风险 - 重新提交 - 1

基本信息

批准号：
10472015
负责人：
Sameer A Ansari
金额：
$ 56.09万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2025-06-30
项目状态：
未结题

项目摘要

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.

项目总结/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)一种新的基于线性时不变系统理论的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。