Is the Relationship between Cortical and White Matter Pathologic Changes in Multiple Sclerosis Spatially Specific? A Multimodal 7-T and 3-T MR Imaging Study with Surface and Tract-based Analysis

Abstract

Purpose:To investigate in vivo the spatial specificity of the interdependence between intracortical and white matter (WM) pathologic changes as function of cortical depth and distance from the cortex in multiple sclerosis (MS), and their independent contribution to physical and cognitive disability. Materials and Methods:This study was institutional review board-approved and participants gave written informed consent. In 34 MS patients and 17 age-matched control participants, 7-T quantitative T2* maps, 3-T T1-weighted anatomic images for cortical surface reconstruction, and 3-T diffusion tensor images (DTI) were obtained. Cortical quantitative T2* maps were sampled at 25%, 50%, 75% depth from pial surface. Tracts of interest were reconstructed by using probabilistic tractography. The relationship between DTI metrics voxelwise of the tracts and cortical integrity in the projection cortex was tested by using multilinear regression models. Results:In MS, DTI abnormal findings along tracts correlated with quantitative T2* changes (suggestive of iron and myelin loss) at each depth of the cortical projection area (P , .01, corrected). This association, however, was not spatially specific because abnormal findings in WM tracts also related to cortical pathologic changes outside of the projection cortex of the tract (P , .001). Expanded Disability Status Scale pyramidal score was predicted by axial diffusivity along the corticospinal tract (b = 4.6 3 10 3 ; P , .001), Symbol Digit Modalities Test score by radial diffusivity along the cingulum (b = 24.3 3 10 4 ; P , .01), and T2* in the cingulum cortical projection at 25% depth (b = 21.7; P , .05). Conclusion:Intracortical and WM injury are concomitant pathologic processes in MS, which are not uniquely distributed according to a tract-cortex-specific pattern; their association may reflect a common stage-dependent mechanism.q RSNA, 2015

The association between intra- and juxta-cortical pathology and cognitive impairment in multiple sclerosis by quantitative T 2 * mapping at 7 T MRI

“…Thirty-one patients (21 females; mean age = 42.4 ± 8.7 SD years) were prospectively recruited in the study from May 2010 to May 2013. This cohort is partly overlapping (31 out of 41 patients) with a cohort from a previously published study in which we found cortical areas characterized by longer q-T 2 * relative to a healthy matched population (Louapre et al, 2016, Louapre et al, 2015, Mainero et al, 2015). The remaining 10 MS subjects were not included due to the lack of NP evaluation at the time of the scanning procedure.…”

Urgent challenges in quantification and interpretation of brain grey matter atrophy in individual MS patients using MRI

“…Furthermore, there are similarities between the average anatomical distribution of GM atrophy and the distributions of both existing WM lesions ( Bodini et al, 2009 ; Muhlau et al, 2013 ; Riccitelli et al, 2012 ) and new WM lesions ( Battaglini et al, 2009 ; Bendfeldt et al, 2010 ). The relation of local GM atrophy to lesional and non-lesional damage in connected WM tracts has only been partially explored ( Bergsland et al, 2015 ; Louapre et al, 2016 ; Steenwijk et al, 2015 ) and further studies are needed to clarify this.…”

Diffusion tensor imaging tractography reveals altered fornix in all diagnostic subtypes of multiple sclerosis

“…Tracts of the limbic system, like the fornix, play crucial roles in aspects of cognition, memory, behavior, and reasoning (Catani & de Schotten, 2012), and they have been implicated in the above whole-brain analyses of MS. Given this relevance, limbic system tracts have been the focus in MS diffusion MRI studies assessed with either region of interest/atlas (Dineen, Bradshaw, Constantinescu, & Auer, 2012;Koenig et al, 2013;Mesaros et al, 2012;Van Geest et al, 2018) or tractography (Fink et al, 2010;Kern et al, 2015;Keser et al, 2017;Louapre et al, 2016;Syc et al, 2013), both targeted analyses that can have distinct advantages over whole-brain voxel-based methods (e.g., far fewer multiple comparisons and do not need intersubject registration for native space tractography). The majority of these DTI studies have been in patients with RRMS, but FA abnormalities in the limbic WM tracts, including the fornix, have also been demonstrated in primary progressive (PPMS; Bodini et al, 2009) and secondary progressive MS (SPMS) (Meijer et al, 2016).…”