IMAGING OF AXONAL DAMAGE IN MULTIPLE-SCLEROSIS - SPATIAL-DISTRIBUTIONOF MAGNETIC-RESONANCE-IMAGING LESIONS

We performed magnetic resonance imaging and magnetic resonance spectro scopic imaging on 28 patients with multiple sclerosis stratified for d isability and clinical course (relapsing with at least partial remissi ons or secondary progressive disease). Lesions were segmented on the c onventional proton density and T2-weighted magnetic resonance images, and lesion distribution images were generated for each patient. The co nventional magnetic resonance and spectroscopic images were transforme d into a standard brain-based stereotaxic coordinate space, allowing c omparison of images from different patients on a voxel-by-voxel basis. The spatial distribution of lesions in the transformed magnetic reson ance images did not differ significantly between the relapsing and the progressive disease groups. We then generated from the individual dat a sets, group lesion probability distribution images for the relapsing and the progressive disease groups. The spatial distribution of metab olites was characterized with respect to lesion distribution using the magnetic resonance spectroscopic images transformed into stereotaxic space and averaged. The neuronal marker N-acetylaspartate was diffusel y lower in the multiple sclerosis patients than in normal control subj ects. Comparison of the averaged metabolite and T2-weighted lesion pro bability images confirmed loss of N-acetylaspartate in regions of both high and low lesion probability. This suggests that diffuse axonal vo lume loss or dysfunction extends beyond the inflammatory lesions of mu ltiple sclerosis, perhaps due to microscopic disease or wallerian dege neration along projection pathways of axons traversing the lesions.