Brain "clean-up crew" visualized by MRI
All parts of the body generate waste that must be flushed out in order to remove harmful materials, old proteins, and other cellular detritus. Most tissues utilize the lymphatic system to keep clean, but the central nervous system (CNS) does not have lymphatic vasculature and relies instead on a waste clearance pathway known as the glymphatic system. The glymphatic system cleans the cerebrospinal fluid (CSF) that surround the brain and spinal cord and relies on specialized CNS support cells known as glia. Here, Helene Benveniste and colleagues at Stony Brook University used MRI to visualize the glymphatic system in rats that had been given a fluorescent tracer. The whole brain images allowed Benveniste and colleagues to identify two key influx nodes in the brain. Additionally, they could measure the rate at which the fluorescent tracer was removed by the glymphatic system. Currently, amyloid plaques and other molecules that accumulate in diseases such as Alzheimer's and Huntington's disease cannot be visualized in live patients. This new technology could potentially be used to track the development or progression of diseases in which the clearance of specific proteins is impaired.
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Abstract
The glymphatic system is a recently defined brain-wide paravascular pathway for cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange that facilitates efficient clearance of solutes and waste from the brain. CSF enters the brain along para-arterial channels to exchange with ISF, which is in turn cleared from the brain along para-venous pathways. Because soluble amyloid β clearance depends on glymphatic pathway function, we proposed that failure of this clearance system contributes to amyloid plaque deposition and Alzheimer’s disease progression. Here we provide proof of concept that glymphatic pathway function can be measured using a clinically relevant imaging technique. Dynamic contrast-enhanced MRI was used to visualize CSF-ISF exchange across the rat brain following intrathecal paramagnetic contrast agent administration. Key features of glymphatic pathway function were confirmed, including visualization of para-arterial CSF influx and molecular size-dependent CSF-ISF exchange. Whole-brain imaging allowed the identification of two key influx nodes at the pituitary and pineal gland recesses, while dynamic MRI permitted the definition of simple kinetic parameters to characterize glymphatic CSF-ISF exchange and solute clearance from the brain. We propose that this MRI approach may provide the basis for a wholly new strategy to evaluate Alzheimer’s disease susceptibility and progression in the live human brain.
Authors
Jeffrey J. Iliff, Hedok Lee, Mei Yu, Tian Feng, Jean Logan, Maiken Nedergaard, Helene Benveniste
Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)