Background and Purpose:
Neuropsychiatric systemic lupus erythematosus (NPSLE) refers to central and peripheral nervous system involvement, which may occur secondary to antineuronal antibodies crossing the blood brain barrier that preferentially target cells in the hippocampus leading to abnormal hypermetabolism and atrophy. Thus, we hypothesize that alterations in BBB permeability (BBBP), detected on DCE-MRI, occurs in the hippocampi in SLE patients prior to development of NPSLE.
Materials and Methods:
Six SLE patients without NPSLE and 5 healthy controls underwent DCE-MRI with post-processing into BBBP parameters (Ktrans, VE) and CBF. Standardized methods selected regions-of-interest (ROIs) sampling the abnormal brain regions detected on FDG-PET. The mean and standard deviation of Ktrans, VE and CBF were calculated. Linear regression and non-parametric Spearman’s rank correlation analyses of Ktrans and VE with CBF were performed. DCE curves and the area under the curve (AUC) were generated for each brain region. Student’s t-test comparisons were performed.
Results:
Quantitative data revealed that SLE patients have statistically increased Ktrans (p<0.001) and VE (p<0.001) compared to controls. In SLE patients, statistically significant positive correlations were seen between Ktrans (p<0.001) and VE (p<0.001) with CBF. Furthermore, the mean AUC revealed statistically increased BBBP in the hippocampus (p=0.02) compared to other brain regions in SLE compared to controls.
Conclusion:
These initial findings are proof-of-concept to support the hypothesis that SLE patients have increased BBBP, specifically in the hippocampus, compared to other brain regions. The significance of these findings may advance our understanding of the underlying pathophysiology affecting the brain in autoimmune diseases.
We report a prospective dynamic contrast-enhanced MR imaging analysis of region-specific blood-brain barrier permeability in 5 healthy subjects. By means of standardized postprocessing and ROI sampling methods, the hippocampi revealed significantly elevated area under the dynamic contrast-enhanced curve and significantly increased blood-brain barrier permeability metrics (volume transfer constant and volume in the extravascular extracellular space) from model-based quantitation. These findings suggest unique blood-brain barrier permeability characteristics in the hippocampus, which are concordant with previous animal studies, potentially laying the groundwork for future studies assessing patient populations in which hippocampal pathology plays a role.
ABBREVIATIONS:BBBP ϭ blood-brain barrier permeability; DCE ϭ dynamic contrast-enhanced; K trans ϭ volume transfer constant; SLE ϭ systemic lupus erythematosus; VE ϭ volume in the extravascular extracellular space Indicates open access to non-subscribers at www.ajnr.org http://dx.
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