Human brain solute transport quantified by glymphatic MRI-informed biophysics during sleep and sleep deprivation

Abstract

ABSTRACTWhether you are reading, running or sleeping, your brain and its fluid environment continuously interacts to distribute nutrients and clear metabolic waste. Yet, the precise mechanisms for solute transport within the human brain have remained hard to quantify using imaging techniques alone. From multi-modal human brain MRI data sets in sleeping and sleep-deprived subjects, we identify and quantify CSF tracer transport parameters using forward and inverse subject-specific computational modelling. Our findings support the notion that extracellular diffusion alone is not sufficient as a brain-wide tracer transport mechanism. Instead, we show that human MRI observations align well with transport by either substantially enhanced (3.5×) extracellular diffusion in combination with local clearance rates corresponding to a tracer half-life of up to 5 hours, or by extracellular diffusion augmented by advection with brain-wide average flow speeds on the order of 1–9µm/min. Reduced advection fully explains reduced tracer clearance after sleep-deprivation, supporting the role of sleep and sleep deprivation on human brain clearance.