Multi-Parametric Imaging of Systemic Cardiovascular and Cerebrovascular Health in Alzheimer's Disease

阿尔茨海默病全身心脑血管健康的多参数成像

基本信息

  • 批准号:
    10370527
  • 负责人:
  • 金额:
    $ 3.57万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-05-01 至 2023-04-30
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Alzheimer’s disease (AD) affects 6 million Americans and is projected to increase to 14 million by the year 2050, with no effective treatment strategies. It is becoming increasingly recognized that AD is multifactorial in nature; the most common mixed dementia pathology is AD amyloid and tau depositions in concert with cerebrovascular disease. However, the exact role of vascular disease in relation to tissue pathology and AD pathogenesis is still uncertain. Magnetic resonance imaging (MRI) is frequently used to observe structural brain changes in AD, but also has the capacity to functionally assess cerebrovascular disease, including cerebral blood flow, pulsatility, perfusion, and white matter lesions of vascular origin. Using 4D flow MRI and pseudo-continuous arterial spin labeling (pCASL), our research group has shown that alterations in cerebrovascular flow and perfusion exist in AD cohorts. We plan to further our vascular imaging territory by utilizing MRI to derive aortic pulse wave velocity (PWV) measures to indirectly asses aortic stiffness, an independent predictor for systemic cardiovascular disease. However, these acquisitions (1) typically require breath-holds to reduce respiratory motion artifacts, which may not be possible in some aging or AD individuals and (2) require high temporal resolution to accurately resolve flow waveforms. Aim 1 is designed to address this by developing a novel, accelerated, free-breathing MR methodology to measure aortic PWV, providing a metric for global cardiovascular health. Specifically, we will employ a radial simultaneous multi-slice (SMS) phase contrast sequence with through-plane encoding and constrained reconstruction to greatly improve resolution capabilities. Aim 2 will validate obtained aortic PWV measurements (from Aim 1) against gold-standard pressure wire measurements with in-vitro testing in 3D printed aortic models and test repeatability of such measures in healthy volunteers. In collaboration with other members at the UW, our research group has implemented methods to probe microvascular pulsatility using displacement encoding stimulated echo (DENSE) sequences as well as measure cerebrovascular PWV using highly- constrained 4D flow reconstructions. Aim 3 seeks to combine cranial 4D flow, pCASL, DENSE, structural brain imaging, and methods from Aim 1, to simultaneously assess multiscale vascular health and structural changes in a group of AD-confirmed and healthy age- and sex-matched controls. This would be the first study to bring together these advanced quantitative MR imaging techniques, providing new insights into vascular disease amongst those with and without AD as well as knowledge of how vascular disease relates to structural changes. Completion of the proposed project and training plan will expand the academic scope of the applicant and foster his goals of becoming an independent investigator focused on translational imaging research.
项目概要 阿尔茨海默病 (AD) 影响着 600 万美国人,预计到 2050 年将增加到 1400 万, 没有有效的治疗策略。人们越来越认识到 AD 本质上是多因素的; 最常见的混合性痴呆病理是 AD 淀粉样蛋白和 tau 蛋白沉积,并伴有脑血管病 疾病。然而,血管疾病与组织病理学和 AD 发病机制相关的确切作用仍不清楚。 不确定。磁共振成像 (MRI) 经常用于观察 AD 患者的大脑结构变化,但是 还具有功能评估脑血管疾病的能力,包括脑血流量、搏动、 灌注和血管起源的白质病变。使用 4D 流 MRI 和伪连续动脉旋转 标记(pCASL),我们的研究小组表明,脑血管血流和灌注的改变存在于 AD 队列。我们计划利用 MRI 推导主动脉脉搏波速度来进一步拓展我们的血管成像领域 (PWV) 间接评估主动脉僵硬度的措施,是全身心血管疾病的独立预测因子 疾病。然而,这些采集 (1) 通常需要屏住呼吸以减少呼吸运动伪影, 这对于某些老年人或 AD 个体来说可能是不可能的,并且 (2) 需要高时间分辨率才能准确地 解析流量波形。目标 1 旨在通过开发一种新颖的、加速的、自由呼吸的方法来解决这个问题 用于测量主动脉 PWV 的 MR 方法,为全球心血管健康提供指标。具体来说,我们 将采用径向同步多切片 (SMS) 相衬序列和平面编码 约束重建大大提高了分辨能力。目标 2 将验证获得的主动脉 PWV 测量(来自目标 1)与 3D 打印体外测试的黄金标准压力线测量 主动脉模型并在健康志愿者中测试此类措施的可重复性。与其他成员合作 在华盛顿大学,我们的研究小组实施了利用位移探测微血管搏动的方法 编码刺激回波(DENSE)序列以及使用高度测量脑血管PWV 约束 4D 流重建。目标 3 寻求将颅脑 4D 流、pCASL、DENSE、结构脑结合起来 成像和目标 1 的方法,同时评估多尺度血管健康和结构变化 在一组经 AD 确诊且年龄和性别匹配的健康对照中。这将是第一项研究 将这些先进的定量 MR 成像技术结合在一起,为血管疾病提供新的见解 患有和没有 AD 的人之间的关系,以及血管疾病如何与结构变化相关的知识。 完成拟议的项目和培训计划将扩大申请人的学术范围并培养 他的目标是成为一名专注于转化成像研究的独立研究者。

项目成果

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Grant S. Roberts其他文献

Vascular contributions to Alzheimer's disease
血管对阿尔茨海默病的贡献
  • DOI:
    10.1016/j.trsl.2022.12.003
  • 发表时间:
    2023-04-01
  • 期刊:
  • 影响因子:
    5.900
  • 作者:
    Laura B. Eisenmenger;Anthony Peret;Bolanle M. Famakin;Alma Spahic;Grant S. Roberts;Jeremy H. Bockholt;Kevin M. Johnson;Jane S. Paulsen
  • 通讯作者:
    Jane S. Paulsen

Grant S. Roberts的其他文献

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