Size-Dependent Transport of Cerebrospinal Fluid Tracers in Mouse Brain Observed by Dynamic Contrast-Enhanced MRI

Recent studies have suggested the glymphatic system as a solute transport pathway and waste removal mechanism in the brain. Imaging intracisternally administered tracers provides the opportunity of assessing various aspects of the glymphatic function in vivo. Dynamic contrast-enhanced MRI allows the evaluation of both the kinetics and spatial distribution of tracer transport throughout the brain. In this study, we investigated the impact of the molecular size of intracisternal tracers on the transport kinetics and distribution in the healthy mouse brain. Three MRI contrast agents with drastically different molecular weights (MWs): 1) Gd-DTPA (MW=661.8 Da), 2) GadoSpin (MW=200 kDa), and 3) oxygen-17 enriched water (H217O, MW=19 Da), were administered via cisterna magna infusion and their transport was dynamically assessed. Our results show that the transport of H217O was significantly faster and more extensive than the two gadolinium-based contrast agents. Time-lagged correlation analysis and clustering analysis comparing the kinetics of Gd-DTPA and H217O transport also showed different cluster patterns and lag time between different regions of the brain. Further, there were also significant differences in the transport kinetics of the three tracers to the lateral ventricles. These observations suggest the size-dependent differences in forces that drive tracer transport in the brain.