High-field contrast-enhanced magnetic resonance imaging demonstrates cerebrospinal fluid nasal efflux dynamics in vivo

Motivation: The astroglia-mediated circulation of metabolites and waste between cerebrospinal fluid (CSF) and blood or lymph, recently termed the glymphatic system, is implicated in processes from autoimmunity to neurodegeneration. Goal(s): Many details of CSF dynamics, particularly efflux routes from brain to periphery including nasal pathways as we examine here, remain to be clarified. Approach: Here we investigate CSF efflux in living mice using 9.4-T in vivo dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Results: We show that gadolinium-based contrast agent injected into the cisterna magna (CM) of live mice dose-rate-dependently effluxes into the nasal mucosa in a manner affected by olfactory neuronal integrity. Impact: Controversy surrounds the current model of CSF efflux from brain ventricles to periphery. We show with high-field DCE-MRI in live mice that nasal efflux of CSF from cisterna magna adapts to both a flow rate challenge and olfactory neuronal damage.