Inflammatory CNS Demyelination: Histopathologic Correlation with In Vivo Quantitative Proton MR Spectroscopy

The mechanisms behind the demyelination that is characteristic of multiple sclerosis (MS) are still poorly understood. The purpose of this study was to compare immunopathologic findings in demyelinating lesions of three patients with in vivo assessments obtained by quantitative proton MR spectroscopy (MRS). Between four and seven stereotactic needle brain biopsies were performed in three young adults with diagnostically equivocal findings for MS. Axonal density, gliosis, blood brain-barrier breakdown, and demyelinating activity of lesions were determined. Combined MR/MRS studies were performed (T1-weighted fast low-angle shot and single-voxel stimulated-echo acquisition mode), and absolute metabolite levels were obtained with a user-independent fitting routine. Metabolite control values were obtained from a group of age-matched healthy volunteers (n = 40, age range, 20-25 years old). Alterations of metabolite levels of control subjects were considered significant when exceeding two standard deviations. There were parallel decreases of N-acetylaspartate (21%-82%) and reductions of axonal density (44%-74%) in demyelinating plaques. Concomitant increases of choline (75%-152%) and myo-inositol (84%-160%) corresponded to glial proliferation. Elevated lactate was associated with inflammation. The present data suggest that in vivo MRS indicates key pathologic features of demyelinating lesions.