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

      The Journal of clinical investigation

      Alzheimer Disease, cerebrospinal fluid, diagnosis, Animals, Brain, metabolism, Cluster Analysis, Contrast Media, administration & dosage, diagnostic use, pharmacokinetics, Extracellular Fluid, Extravasation of Diagnostic and Therapeutic Materials, Female, Gadolinium DTPA, Humans, Injections, Spinal, Magnetic Resonance Imaging, methods, Neuroimaging, Rats, Rats, Sprague-Dawley, Tissue Distribution

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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.

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          Author and article information

          Journal
          23434588
          10.1172/JCI67677
          3582150

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