Developing quantitative biomarkers for monitoring longitudinal changes in brain microvascular health

开发定量生物标志物用于监测大脑微血管健康的纵向变化

• 批准号: 9259432
• 负责人: Alexander Michael Cerjanic
• 金额: $ 4.86万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-16 至 2020-09-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9259432
• 关键词: Age; Aging; Alzheimer' s Disease; Architecture; Biological Markers; Biomedical Computing; Blood; Blood Vessels; Blood Volume; Blood capillaries; Blood flow; Brain; Clinical; Cognition; Cognition Disorders; Cognitive; Computer software; Coupled; Data; Dementia; Detection; Development; Diagnosis; Diffusion; Diffusion Magnetic Resonance Imaging; Disease Progression; Environment; Estimation Techniques; Etiology; Goals; Health; High Performance Computing; Histology; Image; Length; Link; Longitudinal Studies; Magnetic Resonance; Maps; Measurement; Measures; Modeling; Monitor; Motion; Neurodegenerative Disorders; Noise; Output; Patients; Performance; Perfusion; Phase; Physiologic pulse; Pilot Projects; Process; Research Personnel; Sampling; Scheme; Severities; Signal Transduction; Structure; Techniques; Technology; Time; Translating; Validation; Vascular Dementia; Work; aged; base; capillary; cerebral capillary; cerebral microvasculature; clinically relevant; cognitive function; cognitive performance; cohort; density; diffusion weighted; image reconstruction; neuroimaging; novel; open source; population health; research study; software development

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.

项目摘要 在死后研究中观察到大脑微血管随着年龄的变化 使用组织学。这些变化包括长度密度降低、迂曲度增加、血液循环减少、 流动和弦状血管的形成。这些变化的严重性已被观察到， 神经退行性疾病，如阿尔茨海默病。目前，还没有一种既定的方法来衡量 脑中毛细血管和微血管的状态，而不使用侵入性或破坏性组织学。我们 建议使用弥散加权磁共振成像（MRI）来获得定量生物标志物， 测量大脑中微血管的状态。通过创建非侵入性生物标志物来量化 基于逐体素的生物标志物的状态，可以测量随时间的变化。该项目将 开发成像和估计技术来量化这些生物标志物，并进行重要验证 在健康的年轻和老年受试者群体中证明概念验证的步骤。随后 生物标志物将应用于患有阿尔茨海默病的一小群受试者。通过发展小说， 基于神经成像的生物标志物来量化微血管的状态，纵向研究检查 大脑中的微血管变化过程将成为可能。