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Axonal loss in multiple sclerosis lesions: magnetic resonance imaging insights into substrates of disability
J H van Waesberghe1, W Kamphorst, C J De Groot
1MS-MR Centre and Department of Radiology, Academic Hospital Vrije Universiteit, Amsterdam, The Netherlands.
Abstract:
Magnetic resonance imaging (MRI) monitoring of disease progression in multiple sclerosis is limited by the lack of correlation of abnormalities seen on T2-weighted imaging, and disability. We studied the histopathology of multiple sclerosis lesions, as depicted by MRI, in a large postmortem sample, focusing on axonal loss. Tissue samples from 17 patients were selected immediately postmortem for histopathological analysis on the basis of T2-weighted imaging, including normal appearing white matter and T1 hypointense lesions. In each region, we measured magnetization transfer ratios (MTR), T1 contrast ratio, myelin, and axonal density. T2 lesions (109 samples) were heterogeneous with regard to MRI appearance on T1 and MTR, whereas axonal density ranged from 0% (no residual axons) to 100% (normal axonal density). Of 64 T2 lesions, 17 were reactive (mild perivascular inflammation only), 21 active, 15 chronically active, and 11 chronically inactive. MTR and T1 contrast ratio correlated strongly with axonal density. Also in normal appearing white matter (24 samples), MTR correlated with axonal density. In conclusion, postmortem tissue sampling by using MRI revealed a range of pathology, illustrating the high sensitivity and low specificity of T2-weighted imaging. T1 hypointensity and MTR were strongly associated with axonal density, emphasizing their role in monitoring progression in multiple sclerosis.
Insights
Magnetic resonance imaging (MRI) for multiple sclerosis (MS) has limitations. Postmortem analysis shows T1 hypointensity and magnetization transfer ratio (MTR) strongly correlate with axonal density, aiding MS progression monitoring.
Area of Science:
- Neuroimaging
- Neuropathology
- Multiple Sclerosis Research
Background:
- Magnetic resonance imaging (MRI) is crucial for monitoring multiple sclerosis (MS) progression.
- Current T2-weighted imaging lacks direct correlation with patient disability.
- Understanding the histopathology of MS lesions is vital for improving monitoring techniques.
Purpose of the Study:
- To investigate the histopathology of MS lesions using MRI.
- To correlate MRI findings with axonal loss in postmortem tissue samples.
- To evaluate the utility of T1 hypointensity and magnetization transfer ratio (MTR) in assessing MS progression.
Main Methods:
- Postmortem tissue samples from 17 multiple sclerosis patients were analyzed.
- Histopathological analysis included assessment of myelin and axonal density.
- MRI parameters, including T1 contrast ratio and MTR, were measured in different white matter regions.
Main Results:
- T2-weighted lesions exhibited heterogeneity in T1 and MTR characteristics.
- Axonal density varied significantly across lesions, from 0% to 100%.
- Both MTR and T1 contrast ratio showed strong correlations with axonal density, even in normal-appearing white matter.
Conclusions:
- T2-weighted imaging in MS is highly sensitive but lacks specificity.
- T1 hypointensity and MTR are reliable indicators of axonal loss in MS.
- These MRI metrics show promise for monitoring disease progression in multiple sclerosis.