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Updated: May 15, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Gray matter SWI-filtered phase and atrophy are linked to disability in MS
Jesper Hagemeier1, Bianca Weinstock-Guttman, Mari Heininen-Brown
1Department of Neurology, School of Medicine and Biomedical Sciences, Buffalo Neuroimaging Analysis Center, 100 High Street, Buffalo, NY 14203, USA.
Abstract:
The association between clinical outcomes and abnormal susceptibility-weighted imaging (SWI)-filtered phase, indicative of increased iron content, as well as atrophy, was investigated in the subcortical deep-gray matter (SDGM) of multiple sclerosis (MS) patients. 149 relapsing-remitting (RR) and 61 secondary-progressive (SP) MS patients underwent SWI on a 3T scanner. Mean phase of the abnormal phase tissue (MP-APT) and normalized volumes were determined for the total and region-specific SDGM structures. In an age- and gender-adjusted regression model, total SDGM volume was the strongest predictor of Expanded Disability Status Scale (EDSS) (beta = -.224, p<.001), followed by total SDGM MP-APT (beta = -.168, p <.019). This model accounted for 30.4% of the variance in EDSS. Only SDGM MP-APT added additional variance in predicting EDSS, compared to conventional MRI metrics. Caudate and red nucleus MP-APT and amygdala volume were associated with EDSS. Our findings suggest that disability in MS patients is associated better with SDGM pathology, as indicated by increased iron content and atrophy, than with lesion burden or white matter and cortical volumes.
Insights
Subcortical deep-gray matter (SDGM) atrophy and iron accumulation, measured by susceptibility-weighted imaging (SWI), are key indicators of disability in multiple sclerosis (MS) patients. These factors better predict disease progression than traditional MRI metrics.
Area of Science:
- Neuroimaging
- Neurology
- Radiology
Background:
- Multiple sclerosis (MS) is a chronic neurological disease characterized by demyelination and neurodegeneration.
- Subcortical deep-gray matter (SDGM) structures are increasingly recognized as critical sites of pathology in MS.
- Susceptibility-weighted imaging (SWI) can detect iron deposition, a marker of neurodegeneration.
Purpose of the Study:
- To investigate the association between SWI-filtered phase abnormalities (indicating iron content) and atrophy in the SDGM with clinical outcomes in MS patients.
- To determine if SDGM pathology predicts disability progression better than conventional MRI metrics.
Main Methods:
- 149 relapsing-remitting (RR) and 61 secondary-progressive (SP) MS patients underwent SWI on a 3T scanner.
- Mean phase of the abnormal phase tissue (MP-APT) and normalized volumes were quantified for SDGM structures.
- Age- and gender-adjusted regression models were used to assess the association with the Expanded Disability Status Scale (EDSS).
Main Results:
- Total SDGM volume was the strongest predictor of EDSS (beta = -.224, p<.001), followed by total SDGM MP-APT (beta = -.168, p <.019).
- SDGM MP-APT added significant variance in predicting EDSS beyond conventional MRI metrics.
- Specific SDGM regions, including the caudate, red nucleus, and amygdala, showed associations between MP-APT/volume and EDSS.
Conclusions:
- SDGM pathology, encompassing both atrophy and increased iron content (detected by SWI), is significantly associated with disability in MS patients.
- These SWI-derived metrics offer a more sensitive measure of MS-related disability than lesion burden or white matter/cortical volumes.
- SDGM iron content and atrophy are crucial imaging biomarkers for assessing clinical outcomes in MS.
