Human brain MRI reveals more active glymphatic flow in deeper delta sleep

Abstract

Background and aims: The glymphatic system, consisting of water flow in the perivascular space and fluid exchanges between PVS and interstitial space, functions as a wastes clearance system in the brain1. Glymphatic flow is hypothesized to be more active during delta/slow wave sleep, but imaging of human glymphatic function during sleep has not yet been investigated. Methods: Three participants were scanned in a 3 T MRI scanner during their sleep (details in Fig. 1). A 1-h scan consisted of T1-weighted (T1w) and T2w imaging, 8 diffusion imaging (DTI) and 2 diffusion prepared-arterial spin labeling (DP-ASL) imaging sessions (Fig. 1). During DTI and DP-ASL, we performed synchronized EEG recoding and measured the relative delta power during each DTI/DP-ASL session. We then computed ALPS index (water diffusivity ALong the Perivascular Space) on DTI based on a previous protocol2. We also measured water exchange rates across the blood-brain barrier (BBB-kw) using our previously developed method3. [Formula presented] Results: We observed a strong positive correlation between ALPS index and % delta power (r = 0.89, p < 0.0001, Fig. 2B). This result was similar to the result in sleeping mice (Fig. 2A)4. The BBB-kw measured at repeated DP-ASL scans also showed a trend of increased BBB-kw along with a higher delta/slow power (Fig. 2C). [Formula presented] Conclusions: Our findings demonstrate that glymphatic flows measured using the state-of-the-art MRI strongly increase along with deeper delta/(slow) sleep. ALPS and BBB-kw measured at wake and sleep can be surrogate MRI markers for clearance of amyloid beta and an early stage of Alzheimer's disease. [Formula presented]