Relationships of brain white matter microstructure with clinical and MR measures in relapsing-remitting multiple sclerosis

Abstract

Purpose: To assess the relationships of microstructural damage in the cerebral white matter (WM), as measured by diffusion tensor imaging (DTI), with clinical parameters and magnetic resonance imaging (MRI) measures of focal tissue damage in patients with multiple sclerosis (MS).

Materials and methods: Forty-five relapsing-remitting (RR) MS patients (12 male, 33 female; median age = 29 years, Expanded Disability Status Scale (EDSS) = 1.5, disease duration = 3 years) were studied. T2-lesion masks were created and voxelwise DTI analyses performed with Tract-Based Spatial Statistics (TBSS).

Results: T2-lesion volume (T2-LV) was significantly (P < 0.05, corrected) correlated with fractional anisotropy (FA) in both lesions and normal-appearing WM (NAWM). Relationships (P = 0.08, corrected) between increasing EDSS score and decreasing FA were found in the splenium of the corpus callosum (sCC) and along the pyramidal tract (PY). All FA associations were driven by changes in the perpendicular (to primary tract direction) diffusivity. No significant global and voxelwise FA changes were found over a 2-year follow-up.

Conclusion: FA changes related to clinical disability in RR-MS patients with minor clinical disability are localized to specific WM tracts such as the sCC and PY and are driven by changes in perpendicular diffusivity both within lesions and NAWM. Longitudinal DTI measurements do not seem able to chart the early disease course in the WM of MS patients.

Figure 1

Clusters in red-yellow indicate those voxels whose FA values have a significant negative correlation (across patients) with total T2-lesion volume (T2-LV) (A), disease duration (B), number of previous relapses (C), and EDSS score (D). The significant regions have been thickened for better visibility. The green overlay shows the group mean lesion mask. The background image is the group mean FA (in MNI152 standard space). Images are shown in radiological convention. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com].

Figure 2

Yellow clusters represent brain areas with a significant inverse correlation between T2-lesion volume (T2-LV) and FA (ie, where higher T2-LV is correlated with a significant decrease in FA). Regions overlapping with the significant inverse correlation between FA and the number of previous relapses are marked in orange. The significant regions have been thickened for better visibility. The background image is the group mean FA. Images are shown in radiological convention. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com].

Figure 3

Results from multiple regression analysis (see Results for details) show voxels (in red-yellow, thickened for better visibility) where an increase in T2-lesion volume (T2-LV) was significantly correlated with an FA decrease. These voxels colocalize with the left superior corona radiata (SCR) (A) and the right body of the corpus callosum (CC) (B). The significant regions have been thickened for better visibility. Green is the WM skeleton, thresholded at FA >0.3. The background image is the group mean FA. Images are shown in radiological convention. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com].