Modeling glymphatic system and application for aging

项目摘要 长期以来，人们一直认为大脑缺乏传统的淋巴系统。然而，最近的研究导致了 负责将间质溶质移入脑脊液(CSF)的系统的概念化， 主要围绕着静脉，被称为臀部系统。这一系统提供了一条高度组织的途径 驱动间质溶质从脑实质清除的对流流体流动。淋巴系统 在神经系统疾病中起着重要作用。磁共振成像(MRI)是一种合适的无创性检查方法 然而，用于研究这一系统的工具，很少有研究试图对流过臀部的流动进行建模 途径，以便从MRI数据中得出定量参数。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地图 和舌管系统。然后，我们将研究老化对血管和淋巴系统的影响 利用优化后的成像技术对间隙进行分析。大脑老化与动脉硬化有关 动脉顺应性降低，可能导致痴呆症和阿尔茨海默病。由此生成的数据 应用将为脑废物清除的外流途径提供新的见解，并提供足够的 对这一系统进行翻译调查的材料。如果项目的目标实现了，意义重大 患者管理的改进将通过量化淋巴系统和外流途径来实现 导致神经退行性疾病和功能缺陷，如脑外伤、多发性硬化症、出血、 和癫痫。

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.