Association of Blood–Brain Barrier Function With Disease Activity and Cognitive Function in Systemic Lupus Erythematosus Patients

ABSTRACT Background Disruption of the blood–brain barrier ( BBB ) is an important mechanism in the pathogenesis of neuropsychiatric systemic lupus erythematosus ( NPSLE ), potentially influencing disease progression and cognitive function. Purpose To investigate voxel‐wise BBB permeability differences among NPSLE , non‐ NPSLE , and healthy controls ( HC ) using dynamic contrast‐enhanced MRI ( DCE ‐ MRI ), and explore associations with disease activity and cognitive function. Study Type Multicenter, cross‐sectional study. Subjects 22 NPSLE patients, 24 non‐NPSLE patients, and 27 age‐ and sex‐matched HC. Field Strength/Sequence 3.0 Tesla, GE: 3D T1‐FSPGR, DCE‐LAVA‐Flex sequences; Philips: 3D T1‐FFE, eTHRIVE sequences. Assessment Post‐processing of DCE‐MRI images was conducted to calculate the volume transfer constant (K trans ) and plasma volume fraction (V p ) maps, which were transformed to Montreal Neurological Institute space. Brain regions were defined using the Anatomical Automatic Labeling (AAL) atlas. Group differences among NPSLE, non‐NPSLE, and HC were assessed. Mean K trans /V p values from suprathreshold clusters were evaluated for associations with the Disease Activity Index (SLEDAI) and Montreal Cognitive Assessment (MoCA) scores. Mean K trans /V p from corresponding AAL regions was extracted for further validation of the observed correlations. Statistical Tests Voxel‐wise ANOVA with Tukey's HSD test; Spearman correlation and linear regression. Threshold: Voxel‐wise p 20; group comparisons p < 0.05. Results A significantly elevated K trans was observed in the right caudate of NPSLE patients compared to non‐ NPSLE patients, and hippocampal K trans was significantly higher in NPSLE than both non‐ NPSLE and HC . Both NPSLE and non‐ NPSLE patients exhibited widespread significant increases in V p compared to HC . In the entire SLE cohort, right caudate K trans was positively associated with SLEDAI ( ρ = 0.43, R 2 = 0.18) and negatively associated with MoCA scores ( ρ = −0.35, R 2 = 0.12) after adjusting for confounding factors. Data Conclusion This study provided voxel‐level evidence linking regional BBB leakage to both disease activity and cognitive impairment in SLE. Evidence Level 2. Technical Efficacy Stage 2.