Developing quantitative biomarkers for monitoring longitudinal changes in brain microvascular health

项目摘要 在尸检研究中观察到脑微血管随着年龄的变化。 利用组织学。这些变化包括长度密度的减少，弯曲度的增加，血液的减少 流动，并形成管弦管。据观察，这些变化的严重性随着 神经退行性疾病，如阿尔茨海默病。目前，还没有既定的方法来衡量 不使用侵入性或破坏性组织学的大脑中的毛细血管和微血管的状态。我们 建议使用扩散加权磁共振成像(MRI)来提取定量生物标记物 测量大脑中微血管的状态。通过创建非侵入性生物标记物来量化 生物标志物的状态在逐个体素的基础上，可以测量随时间的变化。这个项目将 开发成像和评估技术以量化这些生物标志物，并执行重要的验证 对健康的青年和老年受试者群体进行概念验证的步骤。随后， 生物标记物将应用于一小部分阿尔茨海默病患者。通过开发小说， 基于神经成像的生物标志物用于量化微血管系统的状态，纵向研究检查 脑部微血管变化的过程将成为可能。

Project Summary Changes in the microvasculature of the brain with age have been observed in post-mortem studies using histology. These changes include decreases in length density, increased tortuosity, reductions in blood flow, and formation of string vessels. The severity of these changes has been observed to be greater with neurodegenerative disorders such as Alzheimer's disease. Currently, there is no established way to measure the state of the capillaries and microvessels in the brain without using invasive or destructive histology. We propose to use diffusion weighted Magnetic Resonance Imaging (MRI) to derive quantitative biomarkers to measure the state of the microvasculature in the brain. By creating noninvasive biomarkers to quantify the state of the biomarkers on a voxel-by-voxel basis, changes over time can be measured. This project will develop the imaging and estimation technology to quantify these biomarkers, and perform important validation steps to demonstrate proof of concept on a population of health young and aged subjects. Subsequently, the biomarkers will be applied to a small cohort of subjects with Alzheimer's disease. By developing novel, neuroimaging based biomarkers to quantify the state of the microvasculature, longitudinal studies examining the process of microvascular changes in the brain will be made possible.