Modeling glymphatic system of the brain using MRI.

ABSTRACT

The glymphatic system is functional waste clearance path from the brain parenchyma through dynamic exchange of cerebrospinal fluid (CSF) with interstitial fluid (ISF). Impairment of glymphatic waste clearance is involved in the development of neurodegenerative conditions. Despite many recent studies investigating the glymphatic system, few studies have tried to use a mathematical model to describe this system, quantitatively. In this study, we aim to model the glymphatic system from the kinetics of Gd-DTPA tracer measured using MRI in order to 1) map the glymphatic system path, 2) derive kinetic parameters of the glymphatic system, and 3) provide quantitative maps of the structure and function of this system. In the proposed model, the brain is clustered to similar regions with respect to the profile of contrast agent (CA) density measured by MRI. Then, each region is described as a two-compartment kinetic model 'derived from' or 'clears to' its neighbors with local input function. We thus fit our model to the local cerebral regions rather than to the averaged time signal curve (TSC) of the whole brain. The estimated parameters showed distinctive differences between diabetes mellitus (DM) and control rats. The results suggest that in a typical DM brain the CSF bulk speed in the para-vasculature network is low. In addition, the resulting maps indicate that there may be increased binding and decreased absorbing of large molecules in a diabetic compared with a non-diabetic brain. The important contribution of this work was to fit the model to the local regions rather than to the averaged time signal curve (TSC) of the whole brain. This enabled us to derive quantitative maps of the glymphatic system from MRI.