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

项目摘要/摘要 拟议的工作旨在为申请者准备必要的培训，以建立一个独立的 跨学科生物医学成像科学领域的研究人员，特别关注基于磁共振的 神经退行性疾病的评估。培训的中心核心将涉及缩小 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 以加强对MRI新技术的临床意义和生物医学需求的了解 将影像方法学转化为临床应用。阿尔茨海默病的早期诊断 (AD)对于制定预防、减缓甚至阻止进行性疾病的治疗战略至关重要。一个 越来越多的证据表明，脑血管功能障碍可能发生得相对较早， 阿尔茨海默病患者认知功能减退和神经退行性改变的发生。血管顺应性(VC)或动脉 僵硬是血管功能障碍的重要指标。目前，风险投资只能从中央和 外周动脉采用脉搏波速度(PWV)。最近，我们开发了一种非侵入性核磁共振 动态动脉自旋标记(ASL)评估颅内VC的技术。的目标是 本方案的研究内容是进一步发展和优化无创性颅内静脉 技术，并通过与其他已建立的影像标志物的比较，评价颅内VC作为早期影像标志物的价值 生物标志物。我们推测，颅内静脉可以作为脑血管疾病的早期影像标志。 AD的发展。这些假设将有以下三个具体目标：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 一项测量和比较四个年龄相仿组的颅内VC的横断面研究，包括 认知正常(CN)和轻度认知障碍(MCI)，伴和不伴载脂蛋白E4基因。3)我们 颅内VC与已建立的AD生物标志物相关。预期的结果是一种非侵入性的MRI工具 用于评估颅内VC或动脉僵硬，并将其发展为早期影像 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者提供必要的培训，使其专业知识与临床相结合。 翻译研究并发展成为一名独立的调查员。

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.