Objectives: To quantify, using diffusion tensor imaging (DTI), the tissue damage in lesions and normal-appearing white matter (NAWM) from a large cohort of patients with MS and to investigate the magnitude of the correlation between DTI-derived metrics and clinical disability. Methods: Dual-echo and DTI scans were obtained from 78 patients with relapsing-remitting, secondary progressive, or primary progressive MS and from 20 normal control participants. Post-contrast T1-weighted images were also obtained from the patients. After creating mean diffusivity (D̄) and fractional anisotropy (FA) images and image coregistration, D̄ and FA values were measured for 4846 lesions (3207 nonenhancing T1-isointense, 1511 nonenhancing T1-hypointense, and 128 enhancing), 497 NAWM areas from patients, and 160 white matter areas from the controls. Results: The average lesion D̄ was higher and the average lesion FA was lower than the corresponding quantities of the NAWM (p < 0.001). The D̄ values of enhancing and nonenhancing lesions were not different, whereas enhancing lesions had lower FA (p < 0.001). T1-hypointense lesions had higher D̄ and lower FA than T1-isointense lesions (p < 0.001). NAWM of patients had higher D̄ and lower FA than white matter of controls (p = 0.01). Significant correlations were found between T1 and T2 lesion volume and D̄ and FA of lesions and NAWM. In the overall patient sample, a moderate correlation was also found between lesion D̄ and the Expanded Disability Status Scale score (r = 0.28, p = 0.01). However, the r value of this correlation was 0.48 in patients with secondary progressive MS, whose disability was also correlated with average lesion FA (r = -0.50). Conclusions: The results of this study show that DTI is able to identify MS lesions with severe tissue damage and to detect changes in the NAWM. They also indicate that DTI-derived measures are correlated with clinical disability, especially in patients with secondary progressive MS, thus suggesting a role for DTI in monitoring advanced phases of the disease.
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