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

项目总结 阿尔茨海默氏症(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。人们越来越认识到阿尔茨海默病本质上是多因素的； 最常见的混合性痴呆的病理是AD淀粉样蛋白和tau蛋白沉积，并伴有脑血管 疾病。然而，血管疾病在组织病理学和AD发病机制中的确切作用仍然是 不确定。磁共振成像(MRI)经常被用来观察AD患者大脑结构的变化，但 也有能力对脑血管疾病进行功能性评估，包括脑血流、脉动性、 血流灌注，脑白质血管起源的病变。应用4D Flow MRI和伪连续动脉自旋 标记(PCASL)，我们的研究小组已经表明，脑血管血流和血流灌注的变化存在于 广告队列。我们计划利用核磁共振技术得出主动脉脉搏波速度，以进一步扩大我们的血管成像领域。 (PWV)间接评估主动脉僵硬的措施，这是全身心血管疾病的独立预测指标 疾病。然而，这些采集(1)通常需要屏气以减少呼吸运动伪影， 这在一些老龄化或AD患者中可能是不可能的，以及(2)需要高时间分辨率以准确地 解析流量波形。AIM 1旨在通过开发一种新型的加速自由呼吸来解决这一问题 MR方法测量主动脉PWV，提供全球心血管健康的指标。具体来说，我们 将采用径向同步多切片(SMS)相位对比序列和直通平面编码 有约束的重建，大大提高分辨率能力。AIM 2将验证获得的主动脉PWV 测量(来自AIM 1)对照3D打印的体外测试的金标准压力丝测量 在健康志愿者中建立主动脉模型并测试此类测量的可重复性。与其他成员合作 在威斯康星大学，我们的研究小组已经实施了使用位移来探测微血管搏动的方法 对刺激回声(密集)序列进行编码，并使用高密度编码技术测量脑血管PWV。 受约束的四维流重建。目标3寻求将颅脑4D血流、pCASL、致密、结构性脑 成像和来自目标1的方法，以同时评估多尺度血管健康和结构变化 在一组AD确诊的健康的年龄和性别匹配的对照组中。这将是第一个将 这些先进的定量磁共振成像技术结合在一起，为血管疾病提供了新的见解 在患有和不患有AD的人中，以及对血管疾病如何与结构变化相关的知识。 拟议项目和培训计划的完成将扩大申请者的学术范围并促进 他的目标是成为一名独立研究员，专注于翻译成像研究。

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.