High Resolution and Functional MRI Assessment of Intracranial Atherosclerotic Plaque

描述(申请人提供)：颅内动脉粥样硬化性疾病(ICAD)占急性缺血性中风的7%-10%，在严重颅内狭窄的情况下，中风复发的风险很大，尽管进行了药物治疗，但在1-2年内接近12%-25%。然而，当采用更积极的医疗管理和/或血管内血管成形术/支架的干预可以限制缺血性中风的并发症时，没有风险分层方案可用于靶向治疗试验中识别这一易感人群。我们计划解决的未得到满足的需求是开发和研究磁共振成像方法，该方法可以表征脆弱的炎性和/或血流动力学显著的颅内斑块，对ICAD中原发/复发缺血性卒中的机制和潜在预测因素进行分层。最近，我们利用定量MR灌注技术确定了独特的颅内斑块特征和血流动力学参数，以诊断与症状性颅内狭窄相关的脑血管储备衰竭。我们提出了一项前瞻性研究，招募无症状和有症状的严重ICAD患者，并使用一种全面和新颖的MRI方案对他们进行纵向评估：高分辨率3T磁共振成像、阿魏酸甲酯分子成像、动态对比增强(DCE)MRI定量对比斑块通透性的转移常数(KTRANS)和动态磁化率对比(DSC)MR灌注成像(MR-PWI)使用定量尺度-PWI序列。我们的研究假设是，高分辨率T1斑块增强、T1/T2斑块出血、早期阿魏酸甘油摄取作为巨噬细胞浸润/炎症的标志物、斑块内Ktran通透性和/或改变的qCBF/qCBV血流灌注参数结合血管区域分析将分别有助于区分患者血栓栓塞症和低灌注性缺血并发症的风险。本项目旨在利用先进的高分辨率、分子和功能MRI技术确定特定的定性和定量阈值，这些阈值可与临床表现(无症状、有症状、反复出现症状)、DWI梗塞分布(穿孔、血栓栓子、低灌注性梗塞)、炎性血液标志物以及临床/影像结果相关联，以帮助了解不同的卒中机制，并改进对高危ICAD患者的选择，这些患者尽管进行了积极的治疗，但仍可能容易发生原发或复发的缺血性卒中。

DESCRIPTION (provided by applicant): Intracranial atherosclerotic disease (ICAD) accounts for 7-10% of acute ischemic stroke with a substantial risk of recurrent stroke in a setting of severe intracranial stenosis, approaching 12-25% over 1-2 years despite medical management. However, a risk stratification scheme is not available to identify this susceptible population for targeted treatment trials when intervention with more aggressive medical management and/or endovascular angioplasty/stenting could limit complications of ischemic stroke. The unmet need that we plan to address is to develop and study MR imaging modalities that may characterize vulnerable inflammatory and/or hemodynamically significant intracranial plaques, stratifying the mechanisms and potential predictors of primary/recurrent ischemic stroke in ICAD. Recently, we have identified unique intracranial plaque characteristics as well as hemodynamic parameters using quantitative MR perfusion techniques to stage cerebrovascular reserve failure that are associated with symptomatic intracranial stenoses. We propose a prospective study to recruit asymptomatic and symptomatic patients with severe ICAD and longitudinally assess them with a comprehensive and novel MRI protocol: high resolution 3T MR imaging, ferumoxytol molecular imaging, dynamic contrast enhanced (DCE) MRI to quantify the transfer constant (Ktrans) of contrast plaque permeability, and dynamic susceptibility contrast (DSC) MR perfusion weighted imaging (MR- PWI) using the quantitative SCALE-PWI sequence. Our study hypothesis is that high resolution T1 plaque enhancement, T1/T2 plaque hemorrhage, early ferumoxytol uptake as a marker of macrophage infiltration/inflammation, intraplaque Ktrans permeability, and/or altered qCBF/qCBV perfusion based parameters with vascular territory analysis will assist in stratifying patient risk for thromboembolic versus hypoperfusion related ischemic complications respectively. This project aims to identify specific qualitative and quantitative thresholds with advanced high resolution, molecular, and functional MRI techniques that can be correlated to clinical presentations (asymptomatic, symptomatic, recurrent symptomatic), DWI infarct distributions (perforator, thromboembolic, hypoperfusion related infarcts), inflammatory blood markers, and clinical/imaging outcomes to inform an understanding of differential stroke mechanisms and to improve the selection of high risk ICAD patients who may be susceptible to primary or recurrent ischemic stroke despite aggressive medical management.