Quantitative MRI Demonstrates Abnormality of the Fornix and Cingulum in Multiple Sclerosis

Objective. To characterize MR signal changes associated with tissue damage in the fornix and cingulum in multiple sclerosis (MS) using quantitative MRI measures and to determine associations with cognitive dysfunction. Background. The fornix and cingulum are white-matter bundles that carry information related to cognition. While cognitive dysfunction is reported in 40–60% of MS patients, the neuroanatomical correlates of cognitive impairment remain incompletely understood. Methods. The cingulum, pillars of the fornix, and corticospinal tract were segmented by fiber tracking via diffusion tensor imaging. Average tract-specific fractional anisotropy (FA), mean diffusivity (MD), and magnetization transfer ratio (MTR) were compared in MS cases and healthy volunteers. Associations with clinical measures and neuropsychological tests were derived by multivariate linear regression. Results. Fornix FA (P = 0.004) and MTR (P = 0.005) were decreased, and fornix MD (P < 0.001) and cingulum MD (P < 0.001) increased, in MS cases (n = 101) relative to healthy volunteers (n = 16) after adjustment for age and sex. Lower fornix FA and MTR, and higher fornix MD and λ (||), were correlated with lower PASAT-3 scores, but not with slower 25FTW times. Lower PASAT-3 scores were associated with lower cingulum FA and higher MD and λ (⊥). Conclusions. Cognitive dysfunction in MS may involve damage to a widespread network of brain structures, including white-matter pathways within the limbic system.