Axonal Loss In Multiple Sclerosis Lesions:
MRI Insights Into Substrates Of Disability

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:
1. 17 were reactive
   • Mild PeriVascular inflammation only
2. 21 Active
3. 15 Chronically active
4. 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.