Multimodal MRI reveals glymphatic system activity associated with systemic inflammation and neuropsychiatric symptoms in Crohn's disease.

BACKGROUND: While animal studies suggest that intestinal inflammation can remodel glymphatic function, glymphatic alterations in Crohn's disease (CD) remain poorly understood. This study aims to characterize glymphatic activity in CD patients and explore its associations with systemic inflammation and neuropsychiatric symptoms. METHODS: In this prospective study, we enrolled 89 patients with CD and 48 age- and sex-matched healthy controls (HCs). Glymphatic function was assessed using advanced MRI metrics including free water in white matter (FW-WM), diffusion tensor image analysis along the perivascular space (DTI-ALPS), and global coupling of blood-oxygen-level-dependent with cerebrospinal fluid signals (gBOLD-CSF coupling). General linear models were applied to compare group differences, and partial correlation analyses were conducted to examine the associations of these metrics with inflammatory levels and neuropsychological scores. RESULTS: Compared with HCs, patients with CD showed significantly higher FW-WM, lower DTI-ALPS index, and weaker gBOLD-CSF coupling. Within the CD group, elevated FW-WM was associated with higher CRP levels (r = 0.308, p = 0.021), SAS scores (r = 0.355, p = 0.018), and SDS scores (r = 0.290, p = 0.029), whereas a lower DTI-ALPS index correlated with higher ESR levels (r = - 0.271, p = 0.042) and MFI scores (r = - 0.312, p = 0.021). Furthermore, weaker gBOLD-CSF coupling was significantly associated with higher PSQI scores (r = 0.329, p = 0.021). CONCLUSION: This study provides noninvasive MRI evidence of glymphatic alterations in patients with CD that are associated with systemic inflammation and neuropsychiatric symptoms.