Intracranial Vascular Compliance as an Early Imaging Marker of Alzheimer's Disease

项目总结/摘要 拟议的工作旨在为申请人提供必要的培训，以建立一个独立的 跨学科生物医学成像科学领域的研究者，特别关注基于MRI的 神经退行性疾病的评估。培训的核心将包括缩小以下方面的差距： 申请人的生物物理学背景以及她对病理生理学和临床研究的有限接触， 为了加强对新型MRI技术的临床意义和生物医学需求的理解， 将影像学方法转化为临床应用。早期诊断阿耳茨海默病 (AD)对于开发预防、减缓甚至阻止疾病进展的治疗策略至关重要。一 越来越多的证据表明，脑血管功能障碍可能发生相对较早， 认知下降和AD神经退行性变化的发生。血管顺应性（VC）或动脉 硬度是血管功能障碍的重要指标。目前，风险投资只能从中央和 外周动脉使用脉搏波速度（PWV）。最近，我们开发了一种非侵入性的核磁共振成像技术， 使用动态动脉自旋标记（ASL）评估颅内VC技术。的目标 该提案的研究部分是进一步开发和优化非侵入性颅内VC 技术，并评价颅内VC作为早期影像学标记物与其他建立 生物标志物。我们假设颅内VC能够作为早期影像学标记物， AD的发展。这些假设将以以下三个具体目标进行处理：1）我们将进一步 发展和优化颅内VC技术，提高VC测量的可靠性。2)我们设计 一项横断面研究，旨在测量和比较四个年龄相当组的颅内VC，包括 认知正常（CN）和轻度认知障碍（MCI），有和没有APOE β 4基因型。3)我们 将颅内VC与已建立的AD生物标志物相关联。预期的结果是一种非侵入性的MRI工具 用于评估颅内VC或动脉硬度，并将颅内VC作为早期成像 AD的标志物，这可能加深我们对脑血管在AD发病机制中的作用的理解。这 职业发展奖将为申请人提供必要的培训，将其专业知识与临床 翻译研究，并发展成为一个独立的调查员。

PROJECT SUMMARY/ABSTRACT The proposed work is designed to prepare the applicant with training necessary to establish an independent investigator in the field of interdisciplinary biomedical imaging science, with particular focus on MRI-based assessment of neurodegenerative disease. The central core of the training will involve closing the gap between the applicant's biophysics background and her limited exposure to pathophysiology and clinical research in order to enhance understanding of the clinical implications and biomedical needs of novel MRI techniques toward translating imaging methodology to the clinical applications. Early diagnosis of Alzheimer's disease (AD) is critical for developing therapeutic strategies to prevent, slow or even halt progressive disease. A growing body of evidence suggests cerebrovascular dysfunction may occur relatively early and proceeds the cognitive decline and onset of neurodegenerative changes in AD. Vascular compliance (VC) or arterial stiffness is an important indicator of vascular dysfunction. Currently, VC can be only assessed from central and peripheral arteries using pulse wave velocity (PWV). Recently, we have developed a non-invasive MRI technique for assessment of intracranial VC using dynamic arterial spin labeling (ASL). The goal of the research component of this proposal is to further develop and optimize the noninvasive intracranial VC techniques, and to evaluate intracranial VC as an early imaging marker by comparison with other established biomarkers. We hypothesize that intracranial VC is able to serve as an early imaging marker in the development of AD. The hypotheses will be addressed with the following three specific aims: 1) We will further develop and optimize the intracranial VC technique to improve the reliability of VC measurement. 2) We design a cross-sectional study to measure and compare intracranial VC in four age-equivalent groups including cognitively normal (CN) and mild cognitive impairment (MCI), with and without APOE 4 genotype. 3) We correlate intracranial VC with the established AD biomarkers. The expected outcome is a noninvasive MRI tool for assessment of intracranial VC or arterial stiffness, and developing intracranial VC as an early imaging marker of AD, which may deepen our understanding of cerebrovascular contributions to AD pathogenesis. This career development award will provide the applicant necessary training to integrate her expertise with clinical translational studies and develop into an independent investigator.