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Updated: May 15, 2026
Magnetic Resonance Imaging of Multiple Sclerosis at 7.0 Tesla
Published on: February 19, 2021
Multiple sclerosis: validation of MR imaging for quantification and detection of iron
Andrew J Walsh1, R Marc Lebel, Amir Eissa
1Department of Biomedical Engineering, University of Alberta, 1098 RTF, Edmonton, AB, Canada T6G 2V2.
Purpose:
To investigate the relationship between iron staining and magnetic resonance (MR) imaging measurements in postmortem subjects with multiple sclerosis (MS).
Materials And Methods:
Institutional ethical approval was obtained, and informed consent was obtained from the subjects and/or their families. Four MR imaging methods based on transverse relaxation (T2 weighting, R2 mapping, and R2* mapping) and phase imaging were performed by using a 4.7-T system in three in situ postmortem patients with MS less than 28 hours after death and in one in vivo patient 1 year before death. Iron staining with the Perls iron reaction was performed after brain extraction. Region-of-interest measurements from six subcortical gray matter structures were obtained from MR imaging and then correlated with corresponding locations on photographs of iron-stained pathologic slices by using a separate linear least-squares regression in each subject. Iron status of white matter lesions, as determined by staining, was compared with appearance on MR images.
Results:
R2* mapping had the highest intrasubject correlations with iron in subcortical gray matter (R(2) = 0.857, 0.628, and 0.685; all P < .001), while R2 mapping (R(2) = 0.807, 0.615, 0.628, and 0.489; P < .001 and P = .001, .034, and .001, respectively), phase imaging (R(2) = 0.672, 0.441, 0.596, 0.548; all P ≤ .001), and T2-weighted imaging (R(2) = 0.463, 0.582, 0.650, and 0.551; all P < .001) had lower but still strong correlations. Within lesions, hypointense areas on phase images did not always represent iron. A hyperintense rim surrounding lesions on R2* maps was only present with iron staining, yet not all iron-staining lesions had R2* rim hyperintensity.
Conclusion:
All four MR imaging methods had significant linear correlations with iron and could potentially be used to determine iron status of subcortical gray matter structures in MS, with R2* mapping being preferred. A reliable method of determining iron status within MS lesions was not established.
Insights
Magnetic resonance (MR) imaging, particularly R2* mapping, shows strong correlations with iron staining in multiple sclerosis (MS) gray matter. However, reliably determining iron status within MS lesions using MR imaging remains challenging.
Area of Science:
- Neuroimaging
- Neuropathology
- Biomarkers
Background:
- Iron accumulation is implicated in multiple sclerosis (MS) pathogenesis.
- Magnetic resonance (MR) imaging techniques are sensitive to iron content.
- Postmortem studies can provide valuable insights into MS pathology.
Purpose of the Study:
- To investigate the relationship between iron staining and various MR imaging measurements.
- To assess the utility of different MR imaging techniques for quantifying iron in postmortem MS brains.
- To compare MR imaging findings with histopathological iron staining in subcortical gray matter and white matter lesions.
Main Methods:
- Four MR imaging methods (T2 weighting, R2 mapping, R2* mapping, phase imaging) were applied to postmortem MS brains.
- Iron status was assessed using Perls iron staining.
- Region-of-interest measurements from MR images were correlated with iron staining in subcortical gray matter.
- Iron content in white matter lesions was compared between MR imaging and staining.
Main Results:
- R2* mapping demonstrated the highest correlation with iron in subcortical gray matter (R(2) up to 0.857).
- R2 mapping, phase imaging, and T2-weighted imaging also showed significant correlations with iron, though generally lower than R2*.
- Hypointense areas on phase images did not consistently indicate iron within lesions.
- A hyperintense rim on R2* maps correlated with iron staining, but was not universally present in iron-laden lesions.
Conclusions:
- All four MR imaging methods show significant linear correlations with iron in subcortical gray matter of MS brains.
- R2* mapping is the preferred MR imaging technique for assessing iron status in MS subcortical gray matter.
- A reliable MR imaging method for determining iron status specifically within MS white matter lesions has not yet been established.
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