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Updated: Dec 11, 2025
Magnetic Resonance Imaging of Multiple Sclerosis at 7.0 Tesla
Published on: February 19, 2021
Ex vivo MR microscopy of a human brain with multiple sclerosis: Visualizing individual cells in tissue using
Govind Nair1, Stephen Dodd2, Seung-Kwon Ha3
1Quantitative MRI Core Facility, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, 20892, United States.
Purpose:
To perform magnetic resonance microscopy (MRM) on human cortex and a cortical lesion as well as the adjacent normal appearing white matter. To shed light on the origins of MRI contrast by comparison with histochemical and immunostaining.
Methods:
3D MRM at a nominal isotropic resolution of 15 and 18 µm was performed on 2 blocks of tissue from the brain of a 77-year-old man who had MS for 47 years. One block contained normal appearing cortical gray matter (CN block) and adjacent normal appearing white matter (NAWM), and the other also included a cortical lesion (CL block). Postmortem ex-vivo MRI was performed at 11.7T using a custom solenoid coil and T2*-weighted 3D GRE sequence. Histochemical and immunostaining were done after paraffin embedding for iron, myelin, oligodendrocytes, neurons, blood vessels, macrophages and microglia, and astrocytes.
Results:
MRM could identify individual iron-laden oligodendrocytes with high sensitivity (70% decrease in signal compared to surrounding) in CN and CL blocks, as well as some iron-laden activated macrophages and microglia. Iron-deficient oligodendrocytes seemed to cause relative increase in MRI signal within the cortical lesion. High concentration of myelin in the white matter was primarily responsible for its hypointense appearance relative to the cortex, however, signal variations within NAWM could be attributed to changes in density of iron-laden oligodendrocytes.
Conclusion:
Changes in iron accumulation within cells gave rise to imaging contrast seen between cortical lesions and normal cortex, as well as the patchy signal in NAWM. Densely packed myelin and collagen deposition also contributed to MRM signal changes. Even though we studied only one block each from normal appearing and cortical lesions, such studies can help better understand the origins of histopathological and microstructural correlates of MRI signal changes in multiple sclerosis and contextualize the interpretation of lower-resolution in vivo MRI scans.
Insights
Magnetic resonance microscopy revealed that iron accumulation in oligodendrocytes and myelin density significantly influence MRI contrast in the human brain. These findings help explain MRI signal variations in multiple sclerosis (MS).
Area of Science:
- Neuroimaging
- Histopathology
- Biochemistry
Background:
- Multiple sclerosis (MS) is a demyelinating disease affecting the central nervous system.
- Understanding the origins of MRI contrast is crucial for accurate diagnosis and monitoring of MS.
Purpose of the Study:
- To investigate the origins of MRI contrast in human brain tissue, including cortical lesions and normal-appearing white matter.
- To correlate magnetic resonance microscopy (MRM) findings with histochemical and immunostaining results.
Main Methods:
- Postmortem ex-vivo 3D MRM at 11.7T with 15-18 µm isotropic resolution on human brain tissue.
- Histochemical and immunostaining for iron, myelin, oligodendrocytes, neurons, blood vessels, microglia, and astrocytes.
Main Results:
- MRM identified individual iron-laden oligodendrocytes and activated macrophages/microglia.
- Iron-deficient oligodendrocytes correlated with increased MRI signal in cortical lesions.
- Myelin density and iron accumulation in oligodendrocytes were key determinants of MRM signal intensity and contrast.
Conclusions:
- Cellular iron accumulation and myelin density are major contributors to MRI contrast in MS lesions and normal-appearing white matter.
- These findings enhance the understanding of histopathological correlates of MRI signal changes in MS.
- This study provides context for interpreting lower-resolution in vivo MRI scans in MS patients.
