Magnetic Resonance Imaging and Modeling of the Glymphatic System

Abstract

The glymphatic system is a newly discovered waste drainage pathway in the brain; it plays an important role in many neurological diseases. Ongoing research utilizing various cerebrospinal fluid tracer infusions, either directly or indirectly into the brain parenchyma, is investigating clearance pathways by using distinct imaging techniques. In the present review, we discuss the role of the glymphatic system in various neurological diseases and efflux pathways of brain waste clearance based on current evidence and controversies. We mainly focus on new magnetic resonance imaging (MRI) modeling techniques, along with traditional computational modeling, for a better understanding of the glymphatic system function. Future sophisticated modeling techniques hold the potential to generate quantitative maps for glymphatic system parameters that could contribute to the diagnosis, monitoring, and prognosis of neurological diseases. The non-invasive nature of MRI may provide a safe and effective way to translate glymphatic system measurements from bench-to-bedside.

Keywords: Keywords: glymphatic system; aquaporin-4; bulk flow; cerebrospinal fluid; computational modeling; contrast-enhanced MRI; diffusion; extracellular space; flow pathways; neurological diseases.

Figure 1

Illustration of fluid and interstitial waste solutes movement in the brain between the parenchyma and perivascular spaces surrounding the penetrating vasculature. The periarterial influx in the figure shows the inward movement of CSF along the periarterial space, which mixes with the ISF and interstitial waste solutes in the parenchyma with the help of AQP-4 and gaps between astrocytic end-feet, and then exit via perivenous efflux pathway (along the perivenous space). White arrows indicate the direction of blood flow in the vasculature. Green arrows show the CSF and CSF-ISF fluid transport (whether by diffusion, bulk flow, or both remains elusive). Purple dots indicate the interstitial waste solutes that exit the parenchyma through gaps between the astrocytic end-feet into the perivenous space, which are then drained to the CSF. Reproduced with permission from [15].