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Updated: Mar 24, 2026
Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
The substrate of increased cortical FA in MS: A 7T post-mortem MRI and histopathology study
Laura E Jonkman1, Roel Klaver2, Lazar Fleysher3
1Department of Anatomy & Neurosciences, VU University Medical Center, Amsterdam, The Netherlands le.jonkman@vumc.nl.
Background:
Using diffusion tensor imaging (DTI), it was previously found that demyelinated gray matter (GM) lesions have increased fractional anisotropy (FA) when compared to normal-appearing gray matter (NAGM) in multiple sclerosis (MS). The biological substrate underlying this FA change is so far unclear; both neurodegenerative changes and microglial activation have been proposed as causal contributors.
Objective:
To test the proposed hypothesis that microglia activation is responsible for increased FA in cortical GM lesions.
Methods:
We investigated post-mortem cortical DTI changes in hemispheric, coronally cut sections and investigated the underlying histopathology using immunohistochemistry.
Results:
Overall, there were few activated microglia/macrophages, and no difference between GM lesions and NAGM was observed. However, cell density was increased in GM lesions compared to NAGM (309.67 ± standard deviation (SD) 124.44 vs 249.95 ± SD 56.75, p = 0.002).
Conclusion:
FA increase was not due to lesional and non-lesional differences in microglia activation and/or proliferation. We found an increase in general cellular density without a notable difference in cellular size, that is, tissue compaction, as a possible alternative explanation.
Insights
Microglia activation does not explain increased fractional anisotropy (FA) in multiple sclerosis (MS) gray matter lesions. Instead, increased cell density, or tissue compaction, may account for the observed FA changes in MS.
Area of Science:
- Neuroimaging
- Neuropathology
- Multiple Sclerosis Research
Background:
- Diffusion Tensor Imaging (DTI) studies in multiple sclerosis (MS) show increased fractional anisotropy (FA) in demyelinated gray matter (GM) lesions compared to normal-appearing gray matter (NAGM).
- The underlying biological cause for this FA increase in MS lesions remains unclear, with neurodegeneration and microglial activation being proposed factors.
Purpose of the Study:
- To investigate the hypothesis that microglial activation is the cause of increased FA in cortical GM lesions in MS.
- To explore alternative explanations for FA changes in MS.
Main Methods:
- Post-mortem analysis of cortical DTI changes in human brain sections.
- Immunohistochemistry was used to investigate the underlying histopathology of MS lesions.
- Comparison of cellular density and activation markers between GM lesions and NAGM.
Main Results:
- No significant difference in activated microglia/macrophages was observed between GM lesions and NAGM.
- A significant increase in overall cell density was found in GM lesions compared to NAGM (p=0.002).
- No notable difference in cellular size was detected, suggesting tissue compaction rather than cellular hypertrophy.
Conclusions:
- The increased FA in MS GM lesions is not attributable to microglial activation.
- Increased cellular density, leading to tissue compaction, is a potential explanation for the observed FA increase in MS.
- Further research is needed to fully elucidate the mechanisms behind FA changes in MS gray matter.
