CAPTIVA-MRI

项目摘要/摘要 摘要颅内动脉粥样硬化性狭窄(ICAS)是世界上最常见的缺血性卒中原因，也是卒中复发率最高的疾病(第一年15%的患者)。相比之下，颈动脉狭窄患者的第一年中风复发率为5%，但对颈动脉狭窄有效的内科和外科治疗并不像ICAS那样成功。我们认为，未能预防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，而关注功能血流和ICAS斑块本身将增加关键信息。通过磁共振成像，我们发现ICAS引起的血流动力学损害和破坏，通过相位对比定量MRA和计算流体动态壁切应力来测量，与再发卒中的风险相关。我们还发现血管壁MRI上ICAS斑块强化与再发缺血性卒中之间存在关联。为了进一步探索我们对ICAS血流动力学和斑块生物标记物进行高级MRI测量的范式转换方法，我们将对Captiva进行辅助成像研究，这是一项针对有症状ICAS患者的三臂试验，导致70%-99%的狭窄，随机分配到阿司匹林加替卡格雷、利伐沙班或氯吡格雷。我们的辅助研究Captiva-MRI将确定是否有MRI生物标记物可以识别未能通过最佳医疗管理的ICAS患者，并可以确定ICAS患者的精确药物治疗方法。我们将在基线和1年的随访中对300名Captiva患者进行多模式MRI成像。经过几十年对狭窄的关注，拟议的方法可能会改变ICAS的研究，基于对ICAS如何导致中风的机械性理解。我们已经组建了一个团队，拥有进行前瞻性多中心MRI研究所需的专业知识，包括VERITAS的主要研究人员和无数ICAS的前瞻性多中心MRI研究。家长试验Captiva不包括标准化的脑部或血管成像，这提供了一个明显的机会。这项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.