Brain to Cerebrospinal Fluid Molecular Clearance - Novel Imaging Approaches to Study Brain Waste Management

Through the recent discovery of the glymphatic system, we now begin to understand how the cerebrospinal fluid that surrounds the brain helps to clear away waste products from the brain tissue.

This is of central importance because it can help us understand why proteins accumulate in the brain in dementia diseases.

The glymphatic flow is dependent on the blood vessels and uses spaces around the vessel wall to reach all parts of the brain tissue.

Special channels allow fluid to be pumped in and out of the brain tissue, in a mechanism that can be likened to squeezing dirt out of a sponge in a tub.

However, whether residues flow directly out of the skull or re-mix with the cerebrospinal fluid circulation (the water in the tub) has been uncertain, hampering attempts to design imaging methods to measure glymphatic function in humans.Inspired by reports that the blood-brain barrier leaks small amounts of a clinically used contrast agent we recently investigated whether such contrast delivery allow gauging glymphatic clearance.

Using magnetic resonance imaging, we discovered that intravenous injection caused a small enhancement in cerebrospinal fluid around the brain several hours after the injection - evidence that cleared molecules re-mix with the cerebrospinal fluid circulation where it allows easy detection.In this project, we want to further develop this discovery into a mature imaging method and investigate potential disturbances of the glymphatic system in early dementia.