Brain-wide pathway for waste clearance captured by contrast-enhanced MRI

TLDR

The glymphatic system is a brain‑wide paravascular pathway that exchanges cerebrospinal fluid with interstitial fluid, clearing solutes via para‑arterial influx and para‑venous efflux. The authors propose that impaired glymphatic clearance contributes to amyloid‑β deposition in Alzheimer’s disease and that contrast‑enhanced MRI can serve as a new in‑vivo tool to assess this risk. Dynamic contrast‑enhanced MRI following intrathecal paramagnetic injection visualized CSF‑ISF exchange across the rat brain, revealing para‑arterial influx, size‑dependent exchange, and two key influx nodes at the pituitary and pineal recesses, and enabled kinetic parameter estimation. The study confirmed para‑arterial CSF influx, size‑dependent CSF‑ISF exchange, and demonstrated that glymphatic function can be quantified with clinically relevant imaging.

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.