Abstract
INTRODUCTION: The clearance of brain metabolites increases during sleep, in association with increased spectral power of the three main cerebrospinal fluid (CSF) flow drivers: cardiovascular, respiratory, and vasomotor brain pulsations. However, little is known about how the increased power of these pulsations affects the velocity and direction of fluid flow in the sleeping brain. OBJECTIVES: To address this knowledge gap, we mapped the CSF oscillatory flow velocity in relation to the changing physiological pulsations in the brains of 22 healthy volunteers during sleep and waking. METHODS: We used the ultrafast magnetic resonance imaging sequence known as magnetic resonance encephalography (MREG) for tracing the pulsatile movement of water molecules inside the cranium. First, we conducted a phantom validation study with optical flow analysis to confirm that MREG accurately tracks pulsatile water molecule flow in a porous tissue medium. Next, we obtained MREG recordings for mapping the three physiological pulsations without aliasing in the human brain across the awake and sleep states; we thereby quantified the brain-wide 3D velocity → V vectors (i.e., the velocity v(s) and 3D direction v̂ ) of each pulsation band, using comprehensive dense optical flow analysis during EEG-verified sleep in comparison to the awake state. Finally, we assessed relationships among the spectral power of the physiological pulsations, their 3D velocity → V , and slow-delta EEG power, which is known to depict the increased interstitial volume during sleep. RESULTS: In our phantom study, dense optical flow analysis reliably detected water flow in tissue driven by external pulsations. In healthy volunteers, sleep increased flow velocities ( → V ) of the pulsations by more than 20% in concert with elevations in respiratory pulsations and vasomotor waves, while the velocity of cardiovascular pulsations (v(s)) declined by the same percentage. There was a significant anticorrelation between cardiac mean spectral power and slow delta EEG mean power, and a significant correlation between vasomotor mean spectral power and slow delta EEG mean power over the whole brain. CONCLUSIONS: Phantom studies validated the optic flow analysis of fast MREG recordings. Sleep altered the 3D velocity dynamics of all neurofluidic brain pulsations in a manner consistent with increased interstitial space and greater fluid exchange, thus supporting the glymphatic model wherein physiological pulsations drive bulk flow during sleep.