Quantitative multi-echo T2-based cerebrospinal fluid fraction (CSFF) mapping reveals sleep–wake–dependent brain fluid shifts in healthy adults

BACKGROUND AND PURPOSE: Sleep enhances CSF movement along the perivascular spaces, promoting more efficient clearance of waste from the brain. We determined whether quantitative multi-echo T2-derived cerebrospinal fluid fraction (CSFF) mapping detects sleep-wake-dependent changes in brain free-water compartments in healthy adults. MATERIALS AND METHODS: In this prospective within-subject crossover study, sixteen healthy adults (20-30 years) completed two scan cycles (day cycle with wakeful daytime activity and night cycle with natural nocturnal sleep) separated by a 1-week washout. Each cycle included baseline (precontrast [0 h]) and follow-up (12h after intravenous injection of the GBCA) multi-echo T2 imaging. CSFF maps were computed voxel-wise using multiexponential T2 decomposition to quantify the long T2 (CSF-like) component relative to the total water signal. ROI-based analyses and histogram evaluations were performed in the basal ganglia, frontal, parietal, and occipital cortices, insula, and cerebral WM. Paired comparisons of the relative CSFF changes (12 h - 0 h) between the day and night cycles were performed using the Wilcoxon signed-rank test. During daytime wakefulness, CSFF increased across regions, whereas nighttime sleep was associated with reduced CSFF (left putamen: median, 1.12% [IQR: -3.55 to 10.08] (day) vs. median, -3.41% [IQR: -21.45 to 2.81] (night); left parietal cortex: median, 10.58% [IQR: 6.59 to 14.01] (day) vs. median, -5.91% [IQR: -8.55 to -2.35] (night)). Voxel-wise maps and histogram shifts were consistent with these regional effects. CONCLUSIONS: Quantitative multi-echo T2-based CSFF mapping provides noncontrast, whole-brain, voxel-wise assessment of sleep-wake-related brain fluid redistribution and may serve as an MRI biomarker to probe glymphatic function in humans.