Assessment of glymphatic dysfunction in ulcerative colitis using DKI-ALPS: An innovative imaging biomarker

Ulcerative colitis (UC) is associated with higher anxiety, depression, and cognitive disorders linked to brain glymphatic dysfunction. In this study, we used along-the-perivascular-space (ALPS) index (based on DTI and DKI) to determine if UC relates to glymphatic dysfunction and explore how microbiota dysbiosis and inflammation affect brain glymphatic function.

In this study, 63 patients with UC and 68 healthy controls underwent 3-Tesla MRI scans to evaluate DTI-ALPS and DKI-ALPS index. The protocol included diffusion-weighted imaging (DWI) and diffusion kurtosis imaging (DKI) sequences to calculate the ALPS index, which quantifies glymphatic system function. All participants completed cognitive (MMSE) and depression (SAS/SDS) assessments (SAS/SDS). Patients with UC also underwent assessment for inflammation and gut microbiota (based on metagenomic analysis). Data analysis was performed using correlation analysis and linear regression.

Patients with UC showed lower DTI-ALPS index (1.25) and DKI-ALPS index (1.40) compared to controls (1.40 vs. 1.69; P < 0.001). In multi-adjusted linear regression models, UC was associated with lower DTI-ALPS index and DKI-ALPS index (β =-0.142 vs.-0.284), with DKI-ALPS showing higher sensitivity. The results remained significant even after stratification by age and sex. The Mayo score correlated negatively with DTI and DKI-ALPS index. The ALPS index correlates with gut microbiota, particularly those involved in butyrate and short-chain fatty acid (SCFA) production. DTI-ALPS index was significantly correlated with ESR (β =-0.003), CRP (β =-0.035), SII (β =-0.062), INFLA (β =-0.010), and SIRI (β =-0.058). We also observed significant correlations between DKI ALPS index and ESR (β =-0.006), CRP (β =-0.051), SII (β =-0.130), INFLA (β =-0.017), SIRI (β =-0.095), IL-6 (β =-0.081) and NLR (β =-0.108).

UC is associated with brain glymphatic dysfunction, correlating with inflammation level. DKI-ALPS serves as a more sensitive method than DTI-ALPS, offering a new approach for managing ulcerative colitis through glymphatic dysfunction.