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Updated: Nov 14, 2025
Magnetic Resonance Imaging of Multiple Sclerosis at 7.0 Tesla
Published on: February 19, 2021
QSM is an imaging biomarker for chronic glial activation in multiple sclerosis lesions
Kelly M Gillen1, Mayyan Mubarak2, Calvin Park2
1Department of Radiology, Weill Cornell Medicine, New York, New York, USA.
Background:
Inflammation in chronic active lesions occurs behind a closed blood-brain barrier and cannot be detected with MRI. Activated microglia are highly enriched for iron and can be visualized with quantitative susceptibility mapping (QSM), an MRI technique used to delineate iron.
Objective:
To characterize the histopathological correlates of different QSM hyperintensity patterns in MS lesions.
Methods:
MS brain slabs were imaged with MRI and QSM, and processed for histology. Immunolabeled cells were quantified in the lesion rim, center, and adjacent normal-appearing white matter (NAWM). Iron+ myeloid cell densities at the rims were correlated with susceptibilities. Human-induced pluripotent stem cell (iPSC)-derived microglia were used to determine the effect of iron on the production of reactive oxygen species (ROS) and pro-inflammatory cytokines.
Results:
QSM hyperintensity at the lesion perimeter correlated with activated iron+ myeloid cells in the rim and NAWM. Lesions with high punctate or homogenous QSM signal contained no or minimally activated iron- myeloid cells. In vitro, iron accumulation was highest in M1-polarized human iPSC-derived microglia, but it did not enhance ROS or cytokine production.
Conclusion:
A high QSM signal outlining the lesion rim but not punctate signal in the center is a biomarker for chronic inflammation in white matter lesions.
Insights
Quantitative susceptibility mapping (QSM) can identify chronic inflammation in multiple sclerosis (MS) lesions. A high QSM signal at the lesion rim indicates active inflammation, unlike punctate signals within the lesion center.
Area of Science:
- Neuroimaging
- Neuroinflammation
- Histopathology
Background:
- Inflammation in chronic active multiple sclerosis (MS) lesions is often undetectable by MRI due to the blood-brain barrier.
- Activated microglia, rich in iron, can be visualized using quantitative susceptibility mapping (QSM), an MRI technique.
Purpose of the Study:
- To correlate different QSM hyperintensity patterns in MS lesions with their underlying histopathology.
- To investigate QSM as a potential biomarker for chronic inflammation in MS.
Main Methods:
- MS brain tissue was analyzed using MRI and QSM, followed by histological processing and cell quantification.
- Correlation of iron-positive myeloid cell densities with QSM susceptibilities in lesion rims and normal-appearing white matter (NAWM).
- In vitro studies using human induced pluripotent stem cell (iPSC)-derived microglia to assess iron's effect on reactive oxygen species (ROS) and cytokine production.
Main Results:
- QSM hyperintensity at the lesion perimeter correlated with activated iron-positive myeloid cells in the rim and NAWM.
- Lesions with punctate or homogenous QSM signals showed minimal or no activated iron-negative myeloid cells.
- In vitro, iron accumulated in M1-polarized microglia but did not increase ROS or cytokine production.
Conclusions:
- A high QSM signal delineating the lesion rim serves as a biomarker for chronic inflammation in MS white matter lesions.
- Punctate QSM signals within the lesion center do not indicate chronic inflammation.
