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

纵向和定量 MR 斑块成像用于预测症状性颅内动脉粥样硬化药物治疗的反应

• 批准号: 10366094
• 负责人: Zhaoyang Fan
• 金额: $ 44.63万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10366094
• 关键词: 3-Dimensional; Acceleration; Activities of Daily Living; Acute; Alternative Therapies; Arterial Fatty Streak; Arteries; Atherosclerosis; Blood; Brain; Cerebrospinal Fluid; Clinical; Clinical Research; Clinical Trials; Clinical assessments; Computational algorithm; Consumption; Cross-Sectional Studies; Data Set; Diagnosis; Ensure; Evaluation; Failure; Financial compensation; Fostering; Future; Goals; Human; Image; Imaging Device; Imaging Techniques; Individual; Intracranial Atherosclerotic Disease; Ischemic Stroke; Lesion; Longitudinal Studies; Magnetic Resonance; Medical; Methods; Morphology; Motion; Movement; Patients; Pharmacodynamics; Population; Prediction of Response to Therapy; Recurrence; Reproducibility; Research; Resolution; Risk Factors; Role; Rupture; Scanning; Severities; Signal Transduction; Site; Stenosis; Stroke; Stroke prevention; Techniques; Testing; Three-Dimensional Imaging; Time; Treatment outcome; Validation; Work; base; burden of illness; clinical practice; clinical risk; deep learning; follow-up; high resolution imaging; high risk; imaging approach; imaging modality; improved; morphometry; non-invasive imaging; novel therapeutics; personalized management; predicting response; preservation; prevent; segmentation algorithm; standard of care; tool; validation studies

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.

抽象的 颅内动脉粥样硬化性疾病（ICAD）是全世界缺血性中风的最常见原因之一。 尽管进行了强化医疗管理，但当前中风二级预防的护理标准， 第一年复发性中风的比例为 13%，某些人群在 2 年后高达 35%。目前， 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，并且 某些情况下，管腔狭窄的程度影响影像学。然而，这种策略可能会忽略微妙的 ICAD 病变内的非管腔变化。一种可以直接探测动脉粥样硬化斑块、准确地探测动脉粥样硬化斑块的工具 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，其中 可以开始替代疗法。磁共振 (MR) 血管壁成像 (VWI) 有潜力 发挥这一作用是因为它能够直接可视化血管壁并表征斑块特征。 然而，颅内VWI存在一些技术挑战：体积小、路线曲折、 深度坐位需要高分辨率和 3D 成像方法；多个病变部位需要大 成像视图；来自邻近血液和脑脊液 (CSF) 的信号需要充分 压制；成像时间相对较长，患者运动可能导致图像损坏；和缺乏 特别针对 3D 数据集的专用菌斑分析工具。在本提案中，我们将开发一种可靠的 3D VWI- 基于 MR 斑块成像 (MRPI) 策略，用于预测症状性药物治疗的反应 ICAD。具体来说，我们将首先开发具有颅内血管专用的全脑 3D VWI 序列 运动补偿和运动自适应成像加速（Aim1-Task1）并开发自动化 颅内血管壁 (IVA) 工具集成了 3D 血管壁分割和计算算法 得出定量斑块特征（Aim1-Task2），然后进行验证研究（Aim1-Task3）。经验证的 然后，技术将用于横断面研究，以确定 MRPI 衍生的定量斑块 与急性症状患者梗塞区域内 ICAD 病变相关的特征 ICAD（目标 2）。我们最终将进行纵向研究，以确定纵向和横向的能力 定量 MRPI 预测有症状 ICAD 患者对医疗管理的反应（目标 3）。 该项目的成功完成将验证基于 VWI 的 MRPI 的定量能力 描述 ICAD 的特征并预测有症状的 ICAD 患者对医疗管理的反应。这将打开 未来临床试验的大门，调查 MRPI 在开发个性化管理中的作用 范式和评估新疗法。