Contrast-enhanced MRI T1 Mapping for Quantitative Evaluation of Putative Dynamic Glymphatic Activity in the Human Brain in Sleep-Wake States

Background Evaluation of the glymphatic system with intrathecal contrast material injection has limited clinical use. Purpose To investigate the feasibility of using serial intravenous contrast-enhanced T1 mapping in the quantitative evaluation of putative dynamic glymphatic activity in various brain regions and to demonstrate the effect of sleep on glymphatic activity in humans. Materials and Methods In this prospective study from May 2019 to February 2020, 25 healthy participants (mean age, 25 years ± 2 [standard deviation]; 15 men) underwent two cycles of MRI (day and night cycles). For each cycle, T1 maps were acquired at baseline and 0.5, 1, 1.5, 2, and 12 hours after intravenous contrast material injection. For the night cycle, participants had a normal night of sleep between 2 and 12 hours. The time (t_min) to reach the minimum T1 value (T1_min), the absolute difference between baseline T1 and T1_min (peak ΔT1), and the slope between two measurements at 2 and 12 hours (slope_[2h-12h]) were determined from T1 value-time curves in cerebral gray matter (GM), cerebral white matter (WM), cerebellar GM, cerebellar WM, and putamen. Mixed-model analysis of variance (ANOVA), Friedman test, and repeated-measures ANOVA were used to assess the effect of sleep on slope_(2h-12h) and to compare t_min and peak ΔT1 among different regions. Results The slope_(2h-12h) increased from the day to night cycles in cerebral GM, cerebellar GM, and putamen (geometric mean ratio [night/day] = 1.4 [95% CI: 1.2, 1.7], 1.3 [95% CI: 1.1, 1.4], and 2.4 [95% CI: 1.6, 3.6], respectively; P = .001, P < .001, and P < .001, respectively). Median t_min values were 0.5 hour in cerebral and cerebellar GM and putamen for both cycles. Cerebellar GM had the highest mean peak ΔT1, followed by cerebral GM and putamen in both day (159 msec ± 6, 99 msec ± 4, and 62 msec ± 5, respectively) and night (152 msec ± 6, 104 msec ± 6, and 58 msec ± 4, respectively) cycles. Conclusion Clearance of a gadolinium-based contrast agent was greater after sleep compared with daytime wakefulness. These results suggest that sleep was associated with greater glymphatic clearance compared with wakefulness. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Anzai and Minoshima in this issue.