Abstract
Multiple sclerosis (MS) damages central white matter pathways which has considerable impact on disease-related disability. To identify disease-related alterations in anatomical connectivity, 34 patients (19 with relapsing remitting MS (RR-MS), 15 with secondary progressive MS (SP-MS) and 20 healthy subjects underwent diffusion magnetic resonance imaging (dMRI) of the brain. Based on the dMRI, anatomical connectivity mapping (ACM) yielded a voxel-based metric reflecting the connectivity shared between each individual voxel and all other brain voxels. To avoid biases caused by inter-individual brain-shape differences, they were estimated in a spatially normalized space. Voxel-based statistical analyses using ACM were compared with analyses based on the localized microstructural indices of fractional anisotropy (FA). In both RR-MS and SP-MS patients, considerable portions of the motor-related white matter revealed decreases in ACM and FA when compared with healthy subjects. Patients with SP-MS exhibited reduced ACM values relative to RR-MS in the motor-related tracts, whereas there were no consistent decreases in FA between SP-MS and RR-MS patients. Regional ACM statistics exhibited moderate correlation with clinical disability as reflected by the expanded disability status scale (EDSS). The correlation between these statistics and EDSS was either similar to or stronger than the correlation between FA statistics and the EDSS. Together, the results reveal an improved relationship between ACM, the clinical phenotype, and impairment. This highlights the potential of the ACM connectivity indices to be used as a marker which can identify disease related-alterations due to MS which may not be seen using localized microstructural indices.
Highlights
Multiple sclerosis (MS) is a disease with an inflammatory, demyelinating and neurodegenerative disease course
McDonald criteria [17] participated in this study (Table 1) of whom 19 patients had been diagnosed with the relapsing remitting (RR)-MS disease course, while 15 patients had been diagnosed with the secondary progressive MS (SP-MS) disease course
Using the voxel-based general linear model (GLM) it was found that patients with RRMS and SP-MS had widespread anatomical connectivity mapping (ACM) reductions in all motorrelated white matter (WM) compared to healthy subjects as shown in Figure 1(a) and 1(c)
Summary
Multiple sclerosis (MS) is a disease with an inflammatory, demyelinating and neurodegenerative disease course It diffusely affects the structural and functional integrity of white matter (WM) tracts, contributing to disease-related disability. The poor relation between clinical disability and lesion loads as revealed by T2-weighted MRI has motivated the search for other MRI markers which may reflect more closely the disease-related structural changes leading to disability. The indices have been successfully applied to study microstructural abnormalities in patients with MS, showing reduced FA (increased MD) in MS lesions and normal appearing white matter (NAWM) [6,7,8], presumably reflecting axonal damage [9]. Changes in the DTI indices have been linked to disease-related disability [10] and to specific clinical phenotypes [11]
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