MRI of the corpus callosum in multiple sclerosis: association with disability

Abstract

Inflammatory demyelination and axon damage in the corpus callosum are prominent features of multiple sclerosis (MS) and may partially account for impaired performance on complex tasks. The objective of this article was to characterize quantitative callosal MRI abnormalities and their association with disability. In 69 participants with MS and 29 healthy volunteers, lesional and extralesional callosal MRI indices were estimated via diffusion tensor tractography. expanded disability status scale (EDSS) and MS functional composite (MSFC) scores were recorded in 53 of the participants with MS. All tested callosal MRI indices were diffusely abnormal in MS. EDSS score was correlated only with age (r = 0.51). Scores on the overall MSFC and its paced serial auditory addition test (PASAT) and 9-hole peg test components were correlated with callosal fractional anisotropy (r = 0.27, 0.35, and 0.31, respectively) and perpendicular diffusivity (r = -0.29, -0.30, and -0.31) but not with overall callosal volume or callosal lesion volume; the PASAT score was more weakly correlated with callosal magnetization-transfer ratio (r = 0.21). Anterior callosal abnormalities were associated with impaired PASAT performance and posterior abnormalities with slow performance on the 9-hole peg test. In conclusion, abnormalities in the corpus callosum can be assessed with quantitative MRI and are associated with cognitive and complex upper-extremity dysfunction in MS.

Figure 1. Tractography of the corpus callosum

Regions of interest used for diffusion-tensor-imaging-based tractography were drawn around the corpus callosum on mid-sagittal reformations of the axially acquired data (A) and at the level of the right (B) and left (C) lateral borders of the lateral ventricles. Only the portions of the fibers that traversed these regions of interest were further analyzed. Three-dimensional views of the reconstructed corpus callosum overlaid on FLAIR images in (D) a 36-year-old woman with primary-progressive MS and marked cognitive dysfunction (PASAT-3 score: 27 out of a possible 60) and (E) a 52-year-old man with secondary-progressive MS and even more severe cognitive dysfunction (PASAT-3 score: 15).

Figure 2. Callosal MRI abnormalities in multiple sclerosis

Average spatially normalized tract profiles of the corpus callosum for the healthy-volunteer (gray) and MS (black) cohorts at baseline. Values are adjusted to the average age in our cohort (41.7 years). The horizontal axis uses normalized distance units and is divided into 6 sections corresponding to the different callosal segments; each segment contains 20 equal subsegments. Error bars denote standard errors of the mean. MD, mean diffusivity; λ_||, parallel diffusivity; λ_⊥, perpendicular diffusivity; FA, fractional anisotropy; MTR, magnetization transfer ratio.

Figure 3. Association between callosal fractional anisotropy (FA) and disability scores at baseline

Disability scores were measured within 30 days of MRI scanning in the MS cohort. (A) Paced auditory serial-addition task, 3-second version (PASAT-3). Each data point represents a single participant, and values are averaged across up to 6 scans per participant. Squares, relapsing-remitting MS; circles, secondary-progressive MS; triangles, primary-progressive MS. (B) Association of PASAT-3 with callosal FA within (solid symbols) and outside (open symbols with center dot) callosal lesions. (C) Callosal disability map. Columns represent the z statistic from regressions of disability scores against FA in the whole corpus callosum and individual callosal segments. Negative z statistics correspond to inverse correlations, and the horizontal lines on the plot delineate p=0.05.