Modeling glymphatic system and application for aging

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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.