Altered Blood-Brain Barrier Water Exchange in Remission-Phase Neuromyelitis Optica Spectrum Disorder: A WEPCAST MRI Study.

OBJECTIVE: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease leading to astrocytic and neurovascular unit injury. Although BBB structural disruption during acute attacks is well established, BBB water exchange during clinical remission remains unclear. This study aimed to quantify BBB water exchange in remission phase NMOSD using water-extraction-with-phase-contrast arterial spin labeling (WEPCAST) MRI and compare these findings with those in relapsing remitting multiple sclerosis (RRMS) and healthy controls (HCs). METHODS: Twenty-seven patients with NMOSD (42.5 ± 11.2 years, 27 females), 18 patients with RRMS (36.9 ± 11.9 years, 16 females), and 22 age- and sex-matched HCs (43.1 ± 9.5 years, 22 females) were prospectively enrolled. Remission was defined as no clinical relapse or new MRI lesion within 3 months before imaging. Brain MRI included FLAIR, phase contrast, T1 weighted, and WEPCAST sequences. BBB water exchange was quantified using the WEPCAST derived permeability-surface area product (PS), and quantitative white matter hyperintensity (WMH) volume was assessed on FLAIR images. Pairwise linear regression analyses were used for group comparison with covariate adjustment. RESULTS: NMOSD patients in remission demonstrated significantly higher PS values (141.5 ± 33.7 ml/100 g/min) than RRMS patients (117.8 ± 20.8 mL/100 g/min; p < 0.05) and HCs (120.3 ± 16.8 mL/100 g/min; p < 0.05), whereas RRMS did not differ from HCs. In pairwise regression analyses, PS remained significantly higher in NMOSD than in RRMS and HCs after covariate adjustment and after additional adjustment for WMH volume. CONCLUSION: WEPCAST derived PS is higher in remission phase NMOSD than in RRMS and HCs, suggesting altered BBB water exchange during clinical remission. These exploratory group level findings warrant validation in larger longitudinal cohorts.