CAPTIVA-MRI

项目概要/摘要 颅内动脉粥样硬化性狭窄（ICAS）是世界上缺血性卒中最常见的原因，并且仍然具有最高的卒中复发率（第一年>15%的患者）。相比之下，颈动脉狭窄患者的第一年卒中复发率<5%，但对颈动脉狭窄有效的药物和手术治疗对ICAS不那么成功。我们认为，未能防止ICAS卒中复发反映了狭窄百分比本身并不是风险分层的最佳方法，关注功能性血流和ICAS斑块本身将增加关键信息。使用MRI，我们已经表明，血流动力学损伤和中断所造成的ICAS，测量相位对比定量MRA和计算流体动力学壁切应力，与复发性中风的风险。我们还发现血管壁MRI上ICAS斑块增强与复发性缺血性卒中之间存在相关性。为了进一步探索我们对ICAS血流动力学和斑块生物标志物的高级MRI测量的范式转变方法，我们将对CAPTIVA进行辅助成像研究，CAPTIVA是一项3组试验，在随机分配接受阿司匹林+替格瑞洛、利伐沙班或氯吡格雷治疗的导致70-99%狭窄的症状性ICAS患者中进行。我们的辅助研究CAPTIVA-MRI将确定是否有MRI生物标志物可以识别最佳医疗管理失败的ICAS患者，并可以为ICAS患者确定精确的药物治疗方法。我们将在基线和1年随访访视时对300例CAPTIVA患者的亚组进行多模式MRI成像。在几十年来专注于狭窄之后，基于对ICAS如何导致中风的机械理解，所提出的方法可能会改变ICAS研究。我们组建了一个具有前瞻性多中心MRI研究所需专业知识的团队，包括VERiTAS和MyRIAD ICAS前瞻性多中心MRI研究的主要研究者。母试验CAPTIVA不包括标准化的脑或血管成像，这提供了一个明确的机会。拟议的研究将为未来的研究提供重要和可操作的数据，并将回答有关ICAS进展的关键问题，并为CAPTIVA试验数据集中的各种重要分析提供有价值的MRI数据。

PROJECT SUMMARY/ABSTRACT ABSTRACT Intracranial atherosclerotic stenosis (ICAS) is the most common cause of ischemic stroke in the world and continues to have the highest rate of stroke recurrence (>15% of patients in the first year). In comparison, carotid stenosis has a first-year stroke recurrence rate of <5% of patients, but the medical and surgical treatments that work for carotid stenosis are not as successful for ICAS. We propose that the failure to prevent ICAS stroke recurrence reflects that percentage stenosis alone is not the optimal approach to risk stratification, and that focusing on functional blood flow and the ICAS plaque itself will add critical information. Using MRI, we have shown that hemodynamic impairment and disruption caused by ICAS, measured with phase-contrast quantitative MRA and computational fluid dynamic wall shear stress, is correlated with the risk of recurrent stroke. We have also found an association between ICAS plaque enhancement on vessel wall MRI and recurrent ischemic stroke. To further explore our paradigm shifting approach of advanced MRI measurement of ICAS hemodynamic and plaque biomarkers, we will conduct an ancillary imaging study to CAPTIVA, a 3-arm trial of patients with symptomatic ICAS causing 70-99% stenosis randomly assigned to aspirin plus ticagrelor, rivaroxaban, or clopidogrel. Our ancillary study, CAPTIVA-MRI, will establish if there are MRI biomarkers that can identify ICAS patients who fail best medical management and could identify precision medicine treatment approaches for ICAS patients. We will perform multimodal MRI imaging in a subgroup of 300 CAPTIVA patients at the baseline and the 1-year follow-up visit. After decades of focusing on stenosis, the proposed approach could change ICAS research, based on mechanistic understanding of how ICAS causes stroke. We have assembled a team with the required expertise for a prospective multicenter MRI study, including primary investigators of the VERiTAS and MyRIAD prospective multicenter MRI studies of ICAS. The parent trial, CAPTIVA, does not include standardized brain or vascular imaging, presenting a clear opportunity. The proposed study will provide vital and actionable data for future research and will answer critical questions about ICAS progression and provide valuable MRI data for a wide variety of important analyses in the CAPTIVA trial dataset.