Modeling glymphatic system and application for aging

类淋巴系统建模及其衰老应用

• 批准号: 10372563
• 负责人: Edward Davoodi Boyd
• 金额: $ 19万
• 依托单位: HENRY FORD HEALTH SYSTEM
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10372563
• 关键词: Aging; Alzheimer' s Disease; Animals; Blood Vessels; Brain; Cerebrospinal Fluid; Clinic; Computer Simulation; Confocal Microscopy; Convection; Data; Dementia; Detection; Development; Diagnosis; Disease; Epilepsy; Excision; Gadolinium; Hemorrhage; Image; Imaging Techniques; Impairment; Intercellular Fluid; Investigation; Laser Scanning Confocal Microscopy; Laser Scanning Microscopy; Lymphatic System; Magnetic Resonance Imaging; Maps; Measurement; Mediating; Modeling; Multiple Sclerosis; Names; Nerve Degeneration; Nervous System Trauma; Neurodegenerative Disorders; Pathway interactions; Patients; Play; Predisposition; Rattus; Reproducibility; Resolution; Role; Stroke; Structure; System; Traumatic Brain Injury; Vascular System; Veins; age effect; aging brain; arterial stiffness; base; brain parenchyma; brain pathway; brain tissue; detection sensitivity; ferumoxtran; fluid flow; glymphatic clearance; glymphatic dysfunction; glymphatic system; imaging agent; imaging modality; imaging study; improved; insight; interstitial; iron oxide; kinetic model; longitudinal design; models and simulation; nerve injury; nervous system disorder; novel strategies; real-time images; solute; superparamagnetism; tool; two-photon; wasting

Project Summary Brain was long considered to be devoid of a conventional lymphatic system. However, recent studies led to the conceptualization of a system responsible for the removal of interstitial solute into the cerebrospinal fluid (CSF), mostly around the veins, named, the glymphatic system. This system provides a pathway of highly organized convective fluid flow that drives clearance of interstitial solute from the brain parenchyma. The glymphatic system plays an important role in neurological diseases. Magnetic resonance imaging (MRI) is a suitable non-invasive tool for studying this system, however, few studies have attempted to model the flow through the glymphatic pathways in order to derive quantitative parameters from MRI data. In this project, we will develop, optimize and validate new imaging technique using MRI to derive quantitative maps representing the dynamics of the vascular and glymphatic system. Then, we will investigate aging effects on vascular and glymphatic systems for waste clearance using the optimized imaging technique and analysis. Aging in brain is associated with arterial stiffening and arterial compliance reduction that may led to dementia and Alzheimer disease. Data generated from this application will provide new insights into the efflux pathways of brain waste clearance and provide adequate materials pursuing a translational investigation of this system. If the aims of the project are achieved, significant improvement in patient management will be attained by quantifying the glymphatic system and efflux pathways contribution to neurodegenerative diseases and functional deficits such as TBI, multiple sclerosis, hemorrhage, and epilepsy.

项目摘要 长期以来，人们一直认为大脑没有传统的淋巴系统。然而，最近的研究表明， 概念化负责将间质溶质清除到脑脊液（CSF）中的系统， 主要分布在静脉周围，称为胶质淋巴系统。这个系统提供了一个高度组织化的 驱动间质溶质从脑实质中清除的对流流体流动。glymphatic系统 在神经系统疾病中起着重要作用。磁共振成像（MRI）是一种合适的非侵入性 然而，作为研究该系统的工具，很少有研究试图模拟通过胶质淋巴管的流动。 路径，以便从MRI数据导出定量参数。在这个项目中，我们将开发，优化和 使用MRI验证新的成像技术，以获得代表血管动力学的定量图 和glymphatic系统。然后，我们将研究老化对血管和胶质淋巴系统的影响， 使用优化的成像技术和分析清除。大脑老化与动脉硬化有关 以及动脉顺应性降低，这可能导致痴呆和阿尔茨海默病。由此产生的数据 应用将为脑废物清除的外排途径提供新的见解，并提供足够的 对该系统进行转化研究的材料。如果项目的目标实现， 通过量化胶质淋巴系统和外排途径， 导致神经退行性疾病和功能缺陷，如TBI，多发性硬化，出血， 和癫痫。