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

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.