Abstract: Some patients with systemic lupus erythematosus experience neuropsychiatric symptoms. Although magnetic resonance imaging can detect abnormal signals in the white matter of the brain, conventional methods often struggle to accurately capture microstructural changes. Various diffusion models have been used to study white matter in systemic lupus erythematosus; however, comparative analyses of their sensitivity and specificity for detecting microstructural changes remain insufficient. To address this, our team designed a diagnostic trial that used multimodal diffusion imaging techniques to observe white matter microstructural changes in patients with systemic lupus erythematosus who had neuropsychiatric symptoms, with an aim to identify key diagnostic biomarkers for these patients. Patients with active lupus who received treatment at the Department of Rheumatology and Immunology, The First Affiliated Hospital of China Medical University, from September 2023 to March 2024 were recruited. According to the standards of the American College of Rheumatology, patients with systemic lupus erythematosus who had neuropsychiatric symptoms were assigned to the systemic lupus erythematosus group, whereas those without neuropsychiatric symptoms were assigned to the non-systemic lupus erythematosus group. Additionally, healthy volunteers matched by region, sex, and age were recruited as controls. All three groups underwent the same diffusion magnetic resonance imaging examination protocol to compare differences in diffusion parameters. Advanced diffusion imaging models were able to sensitively detect microstructural changes in the white matter fibers of patients with systemic lupus erythematosus who had neuropsychiatric symptoms, with specific diffusion parameters showing significant abnormalities in key brain regions. In the left superior longitudinal fasciculus subregion and the right thalamic radiations of patients with systemic lupus erythematosus who had neuropsychiatric symptoms, we also identified abnormal diffusion characteristics that were clearly correlated with disease activity, suggesting that microstructural changes in these areas may reflect the dynamic process of neuroinflammatory damage. The present study addresses critical challenges in the diagnosis of systemic lupus erythematosus by identifying specific white matter imaging biomarkers and elucidating the association between microstructural damage and clinical manifestations. The main contributions of our study include: 1) establishing axial regression probability parameters from mean apparent propagator magnetic resonance imaging as sensitive biomarkers for systemic lupus erythematosus, particularly in the third subregion of the left superior longitudinal fasciculus; 2) demonstrating that multimodal diffusion imaging may be superior to conventional diffusion tensor imaging for detecting white matter microstructural abnormalities in patients with systemic lupus erythematosus; and 3) integrating tract-based spatial statistics with clinically relevant analyses to link imaging findings to pathological mechanisms.

Key words: diffusion kurtosis imaging, diffusion tensor imaging, mean apparent propagator, neurite orientation dispersion and density imaging, neuropsychiatric systemic lupus erythematosus, return to axis probability, return to origin probability, superior longitudinal fasciculus-3, superior thalamic radiation, tract-based spatial statistics, white matter microstructure