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Updated: Aug 18, 2025
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Postmortem quantitative MRI disentangles histological lesion types in multiple sclerosis
Riccardo Galbusera1,2, Erik Bahn3, Matthias Weigel1,2,4
1Translational Imaging in Neurology (ThINk) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel and University of Basel, Basel, Switzerland.
Abstract:
Quantitative MRI (qMRI) probes the microstructural properties of the central nervous system (CNS) by providing biophysical measures of tissue characteristics. In this work, we aimed to (i) identify qMRI measures that distinguish histological lesion types in postmortem multiple sclerosis (MS) brains, especially the remyelinated ones; and to (ii) investigate the relationship between those measures and quantitative histological markers of myelin, axons, and astrocytes in the same experimental setting. Three fixed MS whole brains were imaged with qMRI at 3T to obtain magnetization transfer ratio (MTR), myelin water fraction (MWF), quantitative T1 (qT1), quantitative susceptibility mapping (QSM), fractional anisotropy (FA) and radial diffusivity (RD) maps. The identification of lesion types (active, inactive, chronic active, or remyelinated) and quantification of tissue components were performed using histological staining methods as well as immunohistochemistry and immunofluorescence. Pairwise logistic and LASSO regression models were used to identify the best qMRI discriminators of lesion types. The association between qMRI and quantitative histological measures was performed using Spearman's correlations and linear mixed-effect models. We identified a total of 65 lesions. MTR and MWF best predicted the chance of a lesion to be remyelinated, whereas RD and QSM were useful in the discrimination of active lesions. The measurement of microstructural properties through qMRI did not show any difference between chronic active and inactive lesions. MWF and RD were associated with myelin content in both lesions and normal-appearing white matter (NAWM), FA was the measure most associated with axon content in both locations, while MWF was associated with astrocyte immunoreactivity only in lesions. Moreover, we provided evidence of extensive astrogliosis in remyelinated lesions. Our study provides new information on the discriminative power of qMRI in differentiating MS lesions -especially remyelinated ones- as well as on the relative association between multiple qMRI measures and myelin, axon and astrocytes.
Insights
Quantitative MRI measures can differentiate multiple sclerosis (MS) lesion types, particularly remyelinated ones. This study links these MRI measures to myelin, axon, and astrocyte content in MS brain tissue.
Area of Science:
- Neuroimaging
- Neuropathology
- Biophysics
Background:
- Quantitative MRI (qMRI) offers biophysical insights into central nervous system (CNS) microstructural properties.
- Multiple sclerosis (MS) involves complex lesion pathology, including remyelination, which is challenging to characterize non-invasively.
- Understanding the relationship between qMRI metrics and histological tissue components is crucial for accurate MS assessment.
Purpose of the Study:
- To identify qMRI measures capable of distinguishing histological lesion types in postmortem MS brains, with a focus on remyelinated lesions.
- To investigate the correlation between qMRI measures and quantitative histological markers of myelin, axons, and astrocytes within MS lesions and normal-appearing white matter (NAWM).
Main Methods:
- Three fixed MS whole brains were analyzed using 3T qMRI, acquiring Magnetization Transfer Ratio (MTR), Myelin Water Fraction (MWF), quantitative T1 (qT1), Quantitative Susceptibility Mapping (QSM), Fractional Anisotropy (FA), and Radial Diffusivity (RD) maps.
- Lesion types (active, inactive, chronic active, remyelinated) were identified histologically.
- Statistical analyses included logistic regression for lesion discrimination and Spearman correlations/linear mixed-effect models for qMRI-histology associations.
Main Results:
- MTR and MWF were the most effective qMRI measures for predicting remyelinated lesions.
- RD and QSM distinguished active lesions, while no significant qMRI differences were found between chronic active and inactive lesions.
- MWF and RD correlated with myelin content; FA correlated with axon content in both lesions and NAWM; MWF showed association with astrocyte immunoreactivity in lesions, alongside evidence of astrogliosis in remyelinated lesions.
Conclusions:
- qMRI measures, particularly MTR and MWF, demonstrate significant potential in differentiating MS lesion types, especially remyelinated lesions.
- Specific qMRI metrics correlate with myelin, axon, and astrocyte content, offering insights into the microstructural underpinnings of MS pathology.
- The study highlights the utility of qMRI in characterizing MS lesions and provides a foundation for further in vivo investigations.
