Clinically feasible functional MRI providing independent assessments of cerebrovascular stiffness and microcirculation in typical aging and Alzheimer's Disease cohorts

项目摘要/摘要 阿尔茨海默病(AD)是全球痴呆症的主要原因，目前影响着5000多万人。 阿尔茨海默氏症的病理生理机制是复杂的和多因素的，然而，在 脑血管功能与疾病进展有关。尽管血管健康在 AD的预后，评估颅内血管完整性的能力是有限的。迫切需要评估 血管特性对微血管功能和动脉僵硬敏感，以了解血管形成的原因和方式 健康是阿尔茨海默病的一个重要风险因素。正确的工具将能够评估多个脑血管 健康指标和监测针对AD痴呆治疗中的血管系统的潜在干预措施。 本研究旨在利用常规静息功能核磁共振(rs-fmri)扫描来评估动脉僵硬。 通过开发和实施专门的图像处理和微血管健康 技巧。这些指标将应用于从Human Connectome Project获得的两个大型数据集 (HCP)-老龄化和印第安纳州阿尔茨海默病研究中心(IADRC)。使用HCP数据集，我们将 评估典型老化样本中的血管变化(目标1和2)。使用IADRC数据集，我们将评估 脑血管健康与认知功能在认知障碍谱(AIM)中的关系 3)。中心假设是对动脉僵硬和微血管功能敏感的指标 来自专门的RS-fMRI图像处理将显著地与典型的老化和 阿尔茨海默病病理谱系中的认知损害。核心假设将通过 以下目标： 目的1：使用rs-fmri衍生的动脉脉搏评估脑动脉硬度与年龄的相关性。 传播映射。 目的2：在hCP老化数据集中评估由rS-fMRI获得的脑通过时间(CTT)。 目的3：确定rS-fMRI获得的动脉僵硬和AD频谱中的CTT是否显著 与认知障碍有关。 动脉僵硬和微血管功能的测量将提供更好的洞察 血管健康对阿尔茨海默病的影响，并可能在未来用于监测干预状态。整个输油管道 随着在这个项目中开发的详细演示代码将被公开分享，以允许其他研究人员提取 这些血管指标来自标准的rs-fmri数据，并研究其他已知脑血管的病理学。 介入，造成很高的临床影响。

PROJECT SUMMARY/ABSTRACT Alzheimer’s disease (AD) is the leading cause of dementia worldwide currently affecting over 50 million people. The pathophysiology of Alzheimer’s dementia is complex and multifactorial, however, decreases in cerebrovascular function have been linked to disease progression. Despite the role vascular health plays in the prognosis of AD, the ability to assess intracranial vascular integrity is limited. There is a critical need to assess vascular properties sensitive to microvascular function and arterial stiffness to understand why and how vascular health is a substantial risk factor for AD dementia. The right tool will be able to assess multiple cerebrovascular health metrics and monitor potential interventions targeting the vascular system in the treatment of AD dementia. This study aims to utilize a conventional resting-state functional MRI (rs-fMRI) scan to assess arterial stiffness and microvascular health through the development and implementation of specialized image processing techniques. These metrics will be applied to two large datasets available from the Human Connectome Project (HCP) – Aging and the Indiana Alzheimer’s Disease Research Center (IADRC). Using the HCP dataset, we will assess vascular changes in a typically aging sample (aims 1 & 2). With the IADRC dataset, we will assess the associations of cerebrovascular health with cognitive function across a spectrum of cognitive impairment (aim 3). The central hypothesis is that measures sensitive to arterial stiffness and microvascular function derived from specialized rs-fMRI image processing will significantly correlate with typical aging and cognitive impairment in the spectrum of AD pathology. The central hypothesis will be tested with the following aims: Aim 1: Assess the correlation of cerebral artery stiffness and age using rs-fMRI-derived arterial pulse propagation mapping. Aim 2: Evaluate rs-fMRI-derived cerebral transit time (CTT) in the HCP-aging dataset. Aim 3: Determine whether rs-fMRI-derived arterial stiffness and CTT in the AD-spectrum are significantly associated with cognitive impairment. The measures of arterial stiffness and microvascular function will provide greater insight into the influence of vascular health on AD dementia and may be used in the future to monitor intervention status. The entire pipeline with detailed demo code developed in this project will be openly shared to allow other researchers to extract these vascular metrics from standard rs-fMRI data and study other pathologies with known cerebrovascular involvement, resulting in a high clinical impact.