Longitudinal and quantitative MR plaque imaging for prediction of response to medical management in symptomatic intracranial atherosclerosis

摘要 颅内动脉粥样硬化性疾病(ICAD)是世界范围内最常见的缺血性卒中病因之一。 尽管进行了密集的医疗管理，但目前中风二级预防的护理标准， 卒中复发率在第一年为13%，在某些人群中到两年时高达35%。目前， 对这些患者的初始和后续评估完全依赖于对临床风险因素的评估，在 在某些情况下，成像上显示管腔狭窄的程度。然而，这种策略可能忽略了微妙之处。 ICAD病变内的非管腔改变。一种可直接探测动脉粥样硬化斑块并能准确检测的工具 量化斑块特征的纵向变化可能有助于早期识别无反应的患者 可以启动替代疗法。磁共振(MR)血管壁成像(VWI)有可能 发挥这一作用，因为它的紧密性，直接可视化血管壁和表征斑块特征。 然而，与颅内VWI相关的几个技术挑战：体积小，过程曲折， 和深坐需要高分辨率和3D成像方法；多个病变部位需要大量的 影像观点；来自邻近血液和脑脊液(CSF)的信号需要充分 抑制；相对较长的成像时间和患者运动可能导致的图像损坏；以及缺乏 专门的斑块分析工具，特别适用于3D数据集。在这项提案中，我们将开发一种可靠的3D VWI- 基于MR斑块成像(MRPI)策略预测症状性患者的药物治疗反应 ICAD。具体地说，我们将首先开发一种全脑3D VWI序列，该序列具有颅内血管专用 运动补偿和运动自适应成像加速(Aim1-Task1)，并开发了一种自动 集成3D血管壁分割和计算算法的颅内血管壁(IVA)工具 得出定量斑块特征(Aim1-Task2)，然后进行验证研究(Aim1-Task3)。经过验证的 然后，将在横断面研究中使用技术来确定MRPI衍生的定量斑块 急性症状性患者与梗死区内ICAD病变相关的特征 ICAD(目标2)。我们最后将进行纵向研究，以确定纵向和纵向的能力 定量MRPI用于预测有症状的ICAD患者对药物治疗的反应(目标3)。 项目的成功完成将验证基于VWI的MRPI与量化的一致性 描述ICAD的特征并预测对有症状的ICAD患者的药物治疗反应。这将会打开 未来临床试验的大门，调查MRPI在发展个性化管理中的作用 范例和评估新疗法。

ABSTRACT Intracranial atherosclerotic disease (ICAD) is one of the most common causes of ischemic stroke worldwide. Despite intensive medical management, the current standard of care for secondary stroke prevention, the rate of recurrent stroke is 13% in the first year and as high as 35% in certain populations by 2 years. Currently, the initial and follow-up evaluations of these patients rely exclusively on assessments of clinical risk factors and, in some circumstances, the degree of luminal stenosis on imaging. However, this strategy may overlook subtle non-luminal changes within ICAD lesions. A tool that can directly probe atherosclerotic plaques and accurately quantify longitudinal changes of plaque features may help early identify non-responsive patients in whom an alternative therapy can be initiated. Magnetic resonance (MR) vessel wall imaging (VWI) has the potential to fulfill this role because of its compacity to directly visualize the vessel wall and characterize plaque features. However, there are several technical challenges associated with intracranial VWI: small size, tortuous course, and deep sitting warrant a high-resolution and 3D imaging approach; multiple lesion sites require a large imaging view; signals arising from neighboring blood and cerebrospinal fluid (CSF) need to be adequately suppressed; relatively long imaging time and potential image corruption by patient motion; and lack of dedicated plaque analysis tools particularly for 3D dataset. In this proposal, we will develop a reliable 3D VWI- based MR plaque imaging (MRPI) strategy for prediction of response to medical management in symptomatic ICAD. Specifically, we will first develop a whole-brain 3D VWI sequence with intracranial vessel-dedicated motion compensation and motion-adaptive imaging acceleration (Aim1-Task1) and develop an automated intracranial vessel wall (IVA) tool integrating 3D vessel wall segmentation and computational algorithms for deriving quantitative plaque features (Aim1-Task2) followed by a validation study (Aim1-Task3). The validated techniques will then be used in a cross-sectional study to determine the MRPI-derived quantitative plaque features that are associated with ICAD lesions within the infarcted territory in patients with acute symptomatic ICAD (Aim 2). We will finally conduct a longitudinal study to determine the capacity of longitudinal and quantitative MRPI to predict response to medical management in symptomatic ICAD patients (Aim 3). Successful completion of the project will validate the compacity of VWI-based MRPI to quantitatively characterize ICAD and predict response to medical management in symptomatic ICAD patients. This will open the door to future clinical trials investigating the role of MRPI in developing personalized management paradigms and assessing new therapies.