Use of combined conventional and quantitative MRI to quantify pathology related to cognitive impairment in multiple sclerosis

Background: Cognitive impairment is one of the frequent and early findings in multiple sclerosis ( MS). Objective: To determine the relation between cognitive abnormalities and the extent of macroscopic and microscopic tissue damage in the corpus callosum (CC), revealed by conventional magnetic resonance imaging (MRI), magnetisation transfer imaging (MTI) and diffusion tensor imaging (DTI). Methods: Conventional dual-echo, DTI and MTI of the brain were obtained from 36 patients with relapsing remitting (RR) MS, and 13 age and gender matched normal controls. Voxels from CC were identified using a tractography based algorithm. Mean apparent diffusion coefficient (ADCa(fv)) and MT ratio were measured for the CC as defined by tractography. Corpus callosum area (CCA) was measured using edge detection on the midsagittal slice on high resolution MRI images. The Expanded Disability Status Scale (EDSS) and Paced Auditory Serial Addition Test (PASAT) were scored. Results: Nine patients (25%) were found to be cognitively impaired. The CCA was not significantly different in the whole cohort of patients from controls (608.2 (428.6 - 713.0) mm(2) vs 674.2 (585.8 - 754.4) mm2, p = 0.1), but was smaller in cognitively impaired than unimpaired group (417 ( 290 - 634) mm2 vs 652 ( 511 - 718) mm2, p = 0.04). The mean MT ratio of CC in patients was lower than in controls (0.41 (0.39 - 0.042) vs 0.43 (0.42 - 0.43), p, < 0.001). The ADC(av) in the CC in patients was higher than in controls (0.94 (0.89 - 0.99) vs 0.87 (0.85 - 0.89), p, 0.001). PASAT was correlated with mean MT ratio (r = 0.47, p = 0.0046), ADC(av) (r = -0.53, p = 0.0012), CCA (r = 0.42, p = 0.01) and total T-2 lesion load (r = -0.4, p = 0.017), but not with T2 lesion load within the CC ( r= -0.24, p = 0.16), disease duration ( r= 0.2, p= 0.24) or EDSS ( r= -0.27, p= 0.12). Conclusions: ADC(av), MTR and atrophy measures in the CC may offer a sensitive method detecting subtle macroscopic and microscopic changes associated with cognitive impairment in MS.