The Glymphatic System in Humans: Investigations With Magnetic Resonance Imaging

Abstract The concept of the glymphatic system was proposed more than a decade ago as a mechanism for interstitial fluid flow and waste removal in the central nervous system. The function of the glymphatic system has been shown to be particularly activated during sleep. Dysfunction of the glymphatic system has been implicated in several neurodegenerative diseases. Noninvasive in vivo imaging of the glymphatic system is expected to be useful in elucidating the pathophysiology of these diseases. Currently, magnetic resonance imaging is the most commonly used technique to evaluate the glymphatic system in humans, and a large number of studies have been reported. This review provides a comprehensive overview of investigations of the human glymphatic system function using magnetic resonance imaging. The studies can be divided into 3 categories, including imaging without gadolinium-based contrast agents (GBCAs), imaging with intrathecal administration of GBCAs, and imaging with intravenous administration of GBCAs. The purpose of these studies has been to examine not only the interstitial fluid movement in the brain parenchyma, but also the fluid dynamics in the perivascular and subarachnoid spaces, as well as the parasagittal dura and meningeal lymphatics. Recent research has even extended to include the glymphatic system of the eye and the inner ear. This review serves as an important update and a useful guide for future research directions.