Quantitative evaluation of dynamic glymphatic activity in insomnia: A contrast-enhanced synthetic MRI study

Background: Sleep is associated with glymphatic circulation activity; however, there is no direct imaging modality to validate glymphatic circulation disorders in patients with insomnia. Therefore, this study aimed to explore the relationship between insomnia disorder (ID) and the glymphatic system. Dynamic synthetic magnetic resonance imaging (syMRI) was performed. Methods: Thirty-two patients with insomnia and ten healthy volunteers were prospectively recruited from the Second Affiliated Medical Hospital of Nanchang University, China. All subjects underwent syMRI at baseline (0 h), 0.5 h, 1 h, 1.5 h, 12 h, and 3 d after enhancement. The MAGiC post-processing workstation was used to measure T1 signal changes in different brain regions, peak Delta T1, and slopes at different time periods. All patients with insomnia underwent polysomnography (PSG) and were evaluated using the Pittsburgh Sleep Quality Index (PSQI). Repeated measures analysis of variance, Bonferroni multiple comparison, Shapiro-Wilk test, t-test, and Pearson or Spearman correlation analysis were used. Results: The main effect of T1 values for the cerebral white matter, cerebral gray matter, putamen, thalamus, and cerebellar white matter at different measurement times were significant in all subjects (all p < 0.05). The T1 values of the insula gray matter at 0.5 h were statistically different between the insomnia group and the control group (1231.76 f 9.42 vs. 1272.95 f 16.86 ms; p = 0.005), and the T1 values of the hippocampal gray matter at 3 d were different between the two groups (1198.24 f 9.01 vs. 1234.55 f 16.12 ms; p = 0.025). The timevarying curves of the T1 values in the cerebral gray matter and putamen were statistically different between the two groups (p = 0.009, 0.026). The cerebellar gray matter slope (1-1.5 h) and thalamic slope (1-1.5 h) were statistically different between the two groups [-113 (-188.5, -28) vs. 4.739 (-2.07, 7.98); 52 (-10, 119.75) vs. -19.25 (-120, 31.50]; p = 0.048, 0.017). Conclusion: Reduced clearance of the gadolinium-based contrast agent by the gray matter and deep nuclei indicates the presence of glymphatic system impairment in insomnia.