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Abstract #4737

Perivascular cerebrospinal fluid inflow matches interstitial fluid efflux in anesthetized rat brains

Kristian Nygaard Mortensen1, Tuomas Lilius2, Marko Rosenholm3, Björn Sigurðsson3, Douglas Kelley4, and Maiken Nedergaard3
1Danish Research Centre for Magnetic Resonance, Hvidovre Hospital, Hvidovre, Denmark, 2Department of Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland, 3Center for Translational Neuromedicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark, 4Department of Mechanical Engineering, University of Rochester, Rochester, NY, United States

Synopsis

Keywords: Neurofluids, Neurofluids, Extravascular brain clearance

Motivation: No established method exists to quantify cerebrospinal fluid (CSF) inflow to brain tissue, an important driver of brain waste clearance.

Goal(s): We propose a novel method using dynamic contrast-enhanced MRI after tracer infusion in cisterna magna in rats to quantify CSF inflow to a large section of brain tissue.

Approach: CSF perfusion territory, CSF flow velocity and cross-sectional area in the pial perivascular space of the middle cerebral artery are combined to estimate volumetric CSF inflow and compared with interstitial fluid clearance rates.

Results: Both CSF inflow and interstitial fluid clearance are approximately 0.5 µl·g-1·min-1, similar to lymphatic fluid flow in heart tissue.

Impact: Our novel CSF inflow measurement method underscores a probable connection between brain waste clearance and cerebrospinal fluid inflow. It provides a quantitative platform for future biomarkers in both preclinical and clinical investigations of brain waste clearance and CSF circulation.

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