Abstract

To elucidate the mechanism of magnetic resonance (MR) imaging contrast in multiple sclerosis (MS) lesion appearance by using susceptibility-weighted imaging and to assess with histologic correlation the role of iron and myelin in generating this MR imaging contrast. Each patient provided written consent to a human subject protocol approved by an institutional review board. High-spatial-resolution susceptibility-weighted 7.0-T MR images were obtained in 21 patients with MS. Contrast patterns in quantitative phase and R2* images, derived from 7.0-T data, were investigated in 220 areas defined as chronic MS lesions on conventional T2-weighted fluid-attenuated inversion recovery, T2-weighted, and T1-weighted spin-echo images. The presence of positive or negative phase shifts (ie, decreased or increased MR frequency, respectively) was assessed in each lesion. In addition, postmortem MR imaging was performed at 7.0 T and 11.7 T, and its results were correlated with those of immunohistochemical staining specific for myelin, iron, and ferritin. The majority (133 [60.5%] of 220) of the identified lesions had a normal phase and reduced R2*. A substantial fraction of the lesions (84 [38.2%] of 220) had negative phase shift, either uniformly or at their rim, and a variety of appearances on R2* maps. These two lesion contrast patterns were reproduced in the postmortem MR imaging study. Comparison with histologic findings showed that, while R2* reduction corresponded to severe loss of both iron and myelin, negative phase shift corresponded to focal iron deposits with myelin loss. Combined analysis of 7.0-T R2* and phase data may help in characterizing the pathologic features of MS lesions. The observed R2* decreases suggest profound myelin loss, whereas negative phase shifts suggest a focal iron accumulation.

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