HISTOPATHOLOGIC CORRELATE OF HYPOINTENSE LESIONS ON T1-WEIGHTED SPIN-ECHO MRI IN MULTIPLE-SCLEROSIS

Postmortem unfixed whole brains from five multiple sclerosis (RIS) pat ients were examined by MRI using a T2- and T1-weighted spin-echo (SE) sequence and histology to investigate the histopathologic characterist ics of hypointense lesions on T1-weighted SE MR images. The degree of hypointensity was scored semiquantitatively by two blinded observers i n reference to normal-appearing white matter. Signal intensities of th e lesions and the normal-appearing white matter were measured to obtai n contrast ratios. Hematoxylin-eosin stain was used to assess degree o f matrix destruction (decrease of density of the neuropil) and cellula rity of a lesion, Kluver-Barrera stain for degree of demyelination, Bo dian stain for axonal density, and immunostaining of glial fibrillary acid protein for reactive astrocytes and fibrillary gliosis. Nineteen lesions were selected for analysis. Nearly all lesions were compatible with the chronic MS plaque: hypocellularity, absence of myelinated ax ons, in the presence of reactive astrocytes. Contrast ratios of the le sions were highly correlated (R = -0.90; p < 0.01), with degree of hyp ointensity scored semiquantitatively. Degree of hypointensity on T1-we ighted SE images did not correlate with degree of demyelination or num ber of reactive astrocytes, but was associated with axonal density (R = -0.71; p = 0.001). A trend was found with degree of matrix destructi on (R = 0.45; p = 0.052). We conclude that, in our limited sample, hyp ointense lesions seen on T1-weighted SE MR images are associated histo pathologically with severe tissue destruction, including axonal loss. Our results need to be substantiated in a larger study on more varied patient material to evaluate the use of hypointense lesions as a surro gate marker of persistent deficit in MS patients.