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Objectives This study aims to compare the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index, choroid plexus (CP) volume and perivascular space (PVS) volume across different subtypes of neuropsychiatric systemic lupus erythematosus (NPSLE) in order to gain a deeper understanding of brain–immune interfacing dysfunction and neuroinflammation in these patients.Methods A total of 157 patients with SLE (57 non-NPSLE, 57 inflammatory NPSLE and 43 ischaemic NPSLE) and 60 healthy controls (HCs) were enrolled. CP and PVS morphometry were assessed using T1-weighted and T2-weighted images. The DTI-ALPS index was computed to evaluate diffusivity along the x, y and z axes in the lateral ventricle body. Between-group differences in DTI-ALPS and CP/PVS volumes were analysed using analysis of covariance. Receiver operating characteristic (ROC) curve analysis was conducted to differentiate NPSLE and its inflammatory subtype from non-NPSLE. Correlations between imaging data and clinical variables were also examined.Results The DTI-ALPS index is significantly reduced in NPSLE compared with HCs and patients without NPSLE (L: F=10.924, p<0.001; R: F=5.110, p=0.017), particularly in those with inflammatory subtypes. CP volume is significantly higher in patients with SLE than in HCs (L: F=22.273, p<0.001; R: F=21.176, p<0.001). ROC analysis shows moderate diagnostic accuracy for distinguishing non-NPSLE from NPSLE, as well as non-NPSLE from inflammatory NPSLE, when combining the DTI-ALPS index and CP volume (L: area under the curve (AUC)=0.764; R: AUC=0.728). The DTI-ALPS index negatively correlates with ipsilateral CP volume (L: r=−0.315; p<0.001) and positively with Montreal Cognitive Assessment scores (L: r=0.339; p<0.001).Conclusion In conclusion, the DTI-ALPS index and CP volume demonstrate significant potential as neuroimaging biomarkers for NPSLE. They hold promise for differentiating between NPSLE subtypes and shedding light on the underlying mechanisms of central nervous system damage.