CAPTIVA-MRI

CAPTIVA-MRI

• 批准号: 10578494
• 负责人: Sepideh Amin-Hanjani
• 金额: $ 190.66万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-15 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10578494
• 关键词: Address; Affect; African American population; Age; American; Ancillary Study; Angioplasty; Antibody Therapy; Arterial Fatty Streak; Arteries; Asian population; Aspirin; Biological Markers; Black Populations; Blood Vessels; Blood flow; Brain; Carotid Atherosclerotic Disease; Carotid Stenosis; Cerebrovascular system; Coronary Arteriosclerosis; Data; Data Set; Distal; Ensure; Ethnic Origin; Event; Failure; Future; Hispanic Populations; Image; Impairment; Individual; Infarction; Infrastructure; Intervention; Investments; Ischemic Stroke; Knowledge; Liquid substance; MRI Scans; Magnetic Resonance Imaging; Measurement; Measures; Medical; Methods; Modeling; Monoclonal Antibodies; Operative Surgical Procedures; Outcome; Parents; Participant; Patient Selection; Patients; Phase; Public Health; Qualifying; Race; Randomized; Recurrence; Reporting; Research; Research Personnel; Resistance; Resources; Risk; Risk Factors; Standardization; Stenosis; Stents; Stroke; Stroke prevention; Subgroup; System; Techniques; Time; Visit; Visualization; White Matter Hyperintensity; Work; adjudication; cerebrovascular; clopidogrel; disability; effective therapy; follow-up; hemodynamics; high risk; imaging biomarker; imaging study; improved; indexing; lifestyle intervention; magnetic resonance imaging biomarker; multimodality; next generation; novel; novel therapeutic intervention; precision medicine; prevent; primary outcome; prospective; risk stratification; secondary analysis; secondary outcome; sex; shear stress; standard of care; stroke event; three-arm trial; treatment arm; trial design; vascular risk factor

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.

项目概要/摘要 摘要 颅内动脉粥样硬化性狭窄 (ICAS) 是世界上缺血性中风最常见的原因，并且中风复发率仍然最高（第一年患者的复发率>15%）。相比之下，颈动脉狭窄患者的第一年卒中复发率<5%，但针对颈动脉狭窄的药物和手术治疗对于 ICAS 来说并不那么成功。我们认为，预防 ICAS 卒中复发的失败反映出，单独的狭窄百分比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。通过 MRI，我们发现 ICAS 引起的血流动力学损伤和破坏（通过相衬定量 MRA 和计算流体动态壁剪切应力测量）与中风复发的风险相关。我们还发现血管壁 MRI 上的 ICAS 斑块增强与复发性缺血性中风之间存在关联。为了进一步探索我们对 ICAS 血流动力学和斑块生物标志物的先进 MRI 测量的范式转变方法，我们将对 CAPTIVA 进行辅助成像研究，这是一项 3 臂试验，受试者为有症状的 ICAS 患者，导致 70-99% 狭窄，随机分配至阿司匹林加替格瑞洛、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 生物标志物可以识别未能获得最佳医疗管理的 ICAS 患者，并可以为 ICAS 患者确定精准医学治疗方法。我们将在基线和 1 年随访时对 300 名 CAPTIVA 患者组成的亚组进行多模态 MRI 成像。经过数十年对狭窄的关注，基于对 ICAS 如何导致中风的机制的理解，所提出的方法可能会改变 ICAS 研究。我们组建了一支具备前瞻性多中心 MRI 研究所需专业知识的团队，其中包括 VERiTAS 和 ICAS 的 MyRIAD 前瞻性多中心 MRI 研究的主要研究者。母试验 CAPTIVA 不包括标准化的大脑或血管成像，这提供了一个明显的机会。拟议的研究将为未来的研究提供重要且可操作的数据，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。