Objective To quantitatively evaluate blood–brain barrier (BBB) permeability alterations in primary Sjögren’s syndrome (pSS) using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and their associations with clinical immune-inflammatory indicators. Methods In this retrospective study, 19 pSS patients and 23 controls underwent 3.0 T DCE-MRI. BBB permeability was quantified using voxel-wise Ktrans maps on the Patlak model. Whole-brain voxel-wise t-tests were conducted with age and sex as covariates, followed by threshold-free cluster enhancement (TFCE) (1000 permutations, P_TFCE < 0.05) and exploratory uncorrected analysis (P_uncorr < 0.005, cluster ≥ 50 voxels). Whole-brain and ROI Ktrans values were analyzed by ANCOVA with the same covariates. Correlations between regional Ktrans and clinical markers were evaluated by Pearson/Spearman tests and multivariate regression. Results Voxel-wise analysis using TFCE correction (P_TFCE < 0.05) identified significantly elevated Ktrans values in the right cerebellum, whereas exploratory uncorrected analysis (P_uncorr < 0.005, cluster size ≥ 50 voxels) revealed increases in right cerebellum, right temporal pole of the middle temporal gyrus, and right inferior temporal gyrus. No significant differences were observed in whole-brain mean Ktrans (P > 0.05) or ROI Ktrans (all P_uncorr > 0.05). Uncorrected correlations indicated positive associations between regional mean Ktrans and serum globulin, IgM, ESR, and platelets; only limbic Ktrans remained significantly correlated with globulin after FDR correction. Multivariate regression confirmed globulin and ESR as independent predictors of regional Ktrans elevation. Conclusion This study provides the first in vivo DCE-MRI evidence of focal BBB permeability alterations in pSS, potentially associated with immune activation and systemic inflammation. These preliminary findings suggest that DCE-MRI may enable early detection of subclinical central nervous system involvement in pSS and provide insights into its underlying neuroimmunological mechanisms. <Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec colname="c1" colnum="1" /> <colspec colname="c2" colnum="2" /> <tbody> <row> <entry align="left" nameend="c2" namest="c1"> Key Points • First in vivo DCE-MRI evidence of focal BBB permeability alterations in pSS. • Elevated Ktrans values, especially in the right cerebellum, were correlated with serum globulin and ESR levels, suggesting that BBB alterations may be associated with immune activation and systemic inflammation. • DCE-MRI may serve as a sensitive, noninvasive tool for detecting subclinical CNS involvement in pSS. </entry> </row> </tbody> </tgroup> </Table>

Initial assessment of blood–brain barrier permeability alterations and associated clinical characteristics in patients with primary Sjögren’s syndrome: Insights from DCE-MRI

期刊论文
发表日期：

2025年11月14日

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Zhicheng Liu,
Yifan Yang,
Shuang Liu,
Guofang Zhang,
Ruotong Zhao,
Xinyu Xu,
Ru Bai,
Shu Li,
Yuqi Cheng,
Jian Xu

摘要

Objective

To quantitatively evaluate blood–brain barrier (BBB) permeability alterations in primary Sjögren’s syndrome (pSS) using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and their associations with clinical immune-inflammatory indicators.

Methods

In this retrospective study, 19 pSS patients and 23 controls underwent 3.0 T DCE-MRI. BBB permeability was quantified using voxel-wise K^trans maps on the Patlak model. Whole-brain voxel-wise t-tests were conducted with age and sex as covariates, followed by threshold-free cluster enhancement (TFCE) (1000 permutations, P_TFCE < 0.05) and exploratory uncorrected analysis (P_uncorr < 0.005, cluster ≥ 50 voxels). Whole-brain and ROI K^trans values were analyzed by ANCOVA with the same covariates. Correlations between regional K^trans and clinical markers were evaluated by Pearson/Spearman tests and multivariate regression.

Results

Voxel-wise analysis using TFCE correction (P_TFCE < 0.05) identified significantly elevated K^trans values in the right cerebellum, whereas exploratory uncorrected analysis (P_uncorr < 0.005, cluster size ≥ 50 voxels) revealed increases in right cerebellum, right temporal pole of the middle temporal gyrus, and right inferior temporal gyrus. No significant differences were observed in whole-brain mean K^trans (P > 0.05) or ROI K^trans (all P_uncorr > 0.05). Uncorrected correlations indicated positive associations between regional mean K^trans and serum globulin, IgM, ESR, and platelets; only limbic K^trans remained significantly correlated with globulin after FDR correction. Multivariate regression confirmed globulin and ESR as independent predictors of regional K^trans elevation.

Conclusion

This study provides the first in vivo DCE-MRI evidence of focal BBB permeability alterations in pSS, potentially associated with immune activation and systemic inflammation. These preliminary findings suggest that DCE-MRI may enable early detection of subclinical central nervous system involvement in pSS and provide insights into its underlying neuroimmunological mechanisms.

Key Points

• First in vivo DCE-MRI evidence of focal BBB permeability alterations in pSS.

• Elevated Ktrans values, especially in the right cerebellum, were correlated with serum globulin and ESR levels, suggesting that BBB alterations may be associated with immune activation and systemic inflammation.

• DCE-MRI may serve as a sensitive, noninvasive tool for detecting subclinical CNS involvement in pSS.