Associations between Paramagnetic Rim Lesions and Gadolinium Contrast Permeability of Perivascular Spaces in Patients...

Paramagnetic rim lesions (PRLs) are established biomarkers of chronic active inflammation in patients with multiple sclerosis (MS). Gadolinium enhancement in basal ganglia perivascular spaces (BGPVS), reflecting blood-brain barrier (BBB) permeability, represents an emerging but underexplored marker of neurovascular dysfunction. This study primarily investigated whether PRL burden is independently associated with BGPVS gadolinium enhancement. Secondarily, choroid plexus (CP) volume and the DTI-based Analysis along the Perivascular Space (ALPS) index were compared between patients with MS and healthy controls as exploratory glymphatic markers.

This retrospective study (Nov 2023-Aug 2024) included patients with MS and age- and sex-matched controls who underwent 3T MRI with pre- and post-contrast T1 mapping and quantitative susceptibility mapping (QSM). PRLs were counted on QSM. Post-gadolinium BGPVS T1 enhancement, white matter hyperintensity (WMH) volume, CP volume fraction, and the ALPS index were quantified. Correlation, partial correlation adjusted for age and sex, and multivariable Poisson regression analyses with Benjamini-Hochberg false discovery rate correction identified predictors of PRL burden.

A total of 144 patients with MS (mean age, 44 years ± 13 years; 105 females) and 34 controls (mean age, 49.9 years ± 16.6 years; 18 females) were evaluated. Compared with the controls, patients with MS had a lower ALPS index (1.44 ± 0.20 vs 1.56 ± 0.17; P=0.01), higher CP volume fraction (0.21% ± 0.05% vs 0.19% ± 0.04%; P=0.04), and greater BGPVS enhancement (absolute ΔT1, 92.8 ms ± 22.9 ms vs 80.7 ms ± 16.8 ms; P=0.02). The PRL count was negatively correlated with age (r=-0.378, P<0.001) and positively correlated with WMH volume (r=0.437, P<0.001) and BGPVS enhancement (r=0.219, P=0.02). After adjusting for age and sex, partial correlations confirmed significant associations between PRL count and WMH volume (r=0.477, q<0.001), CP volume fraction (r=0.297, q<0.001), and BGPVS enhancement (r=0.346, q<0.001). Multivariable Poisson regression confirmed younger age (IRR=0.91, P<0.001), higher WMH volume (IRR=1.87, P<0.001), CP volume fraction (IRR=1.46, P<0.001), and BGPVS enhancement (IRR=1.47, P<0.001) as independent predictors of PRL count.

PRL burden is independently associated with increased gadolinium permeability of BGPVS, linking focal chronic active inflammation to broader blood-brain-barrier dysfunction in patients with MS.