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Updated: Mar 27, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Grey Matter Atrophy in Multiple Sclerosis: Clinical Interpretation Depends on Choice of Analysis Method
Veronica Popescu1, Menno M Schoonheim2, Adriaan Versteeg1
1Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (NCA), VU University Medical Center, Amsterdam, The Netherlands.
Background:
Studies disagree on the location of grey matter (GM) atrophy in the multiple sclerosis (MS) brain.
Aim:
To examine the consistency between FSL, FreeSurfer, SPM for GM atrophy measurement (for volumes, patient/control discrimination, and correlations with cognition).
Materials And Methods:
127 MS patients and 50 controls were included and cortical and deep grey matter (DGM) volumetrics were performed. Consistency of volumes was assessed with Intraclass Correlation Coefficient/ICC. Consistency of patients/controls discrimination was assessed with Cohen's d, t-tests, MANOVA and a penalized double-loop logistic classifier. Consistency of association with cognition was assessed with Pearson correlation coefficient and ANOVA. Voxel-based morphometry (SPM-VBM and FSL-VBM) and vertex-wise FreeSurfer were used for group-level comparisons.
Results:
The highest volumetry ICC were between SPM and FreeSurfer for cortical regions, and the lowest between SPM and FreeSurfer for DGM. The caudate nucleus and temporal lobes had high consistency between all software, while amygdala had lowest volumetric consistency. Consistency of patients/controls discrimination was largest in the DGM for all software, especially for thalamus and pallidum. The penalized double-loop logistic classifier most often selected the thalamus, pallidum and amygdala for all software. FSL yielded the largest number of significant correlations. DGM yielded stronger correlations with cognition than cortical volumes. Bilateral putamen and left insula volumes correlated with cognition using all methods.
Conclusion:
GM volumes from FreeSurfer, FSL and SPM are different, especially for cortical regions. While group-level separation between MS and controls is comparable, correlations between regional GM volumes and clinical/cognitive variables in MS should be cautiously interpreted.
Insights
Grey matter (GM) atrophy measurements in multiple sclerosis (MS) brains vary across software. While software can distinguish MS patients from controls, correlations with cognition require cautious interpretation due to differing results.
Area of Science:
- Neuroimaging
- Neurology
- Medical image analysis
Background:
- Multiple Sclerosis (MS) brain grey matter (GM) atrophy location is inconsistently reported.
- Discrepancies exist in studies examining GM atrophy in MS.
Purpose of the Study:
- To assess the consistency of grey matter (GM) atrophy measurements using FSL, FreeSurfer, and SPM in multiple sclerosis (MS) brains.
- To compare volumetric data, patient/control discrimination, and cognitive correlations across different neuroimaging analysis software.
Main Methods:
- Included 127 MS patients and 50 controls for cortical and deep grey matter (DGM) volumetrics.
- Assessed volume consistency using Intraclass Correlation Coefficient (ICC).
- Evaluated patient/control discrimination and cognitive associations using statistical tests and machine learning classifiers.
Main Results:
- Highest volumetric ICC between SPM and FreeSurfer for cortical regions; lowest for DGM.
- Caudate nucleus and temporal lobes showed high consistency; amygdala showed low consistency.
- Deep grey matter (DGM) demonstrated better patient/control discrimination and stronger cognitive correlations than cortical volumes.
Conclusions:
- Grey matter (GM) volumes derived from FreeSurfer, FSL, and SPM differ, particularly in cortical regions.
- While software can differentiate MS patients from controls, correlations between regional GM volumes and clinical/cognitive variables in MS warrant careful consideration.
