Exploring the relationship between white matter and gray matter damage in early primary progressive multiple sclerosis: An in vivo study with TBSS and VBM

Abstract

We investigated the relationship between the damage occurring in the brain normal-appearing white matter (NAWM) and in the gray matter (GM) in patients with early Primary Progressive multiple sclerosis (PPMS), using Tract-Based Spatial Statistics (TBSS) and an optimized voxel-based morphometry (VBM) approach. Thirty-five patients with early PPMS underwent diffusion tensor and conventional imaging and were clinically assessed. TBSS and VBM were employed to localize regions of lower fractional anisotropy (FA) and lower GM volume in patients compared with controls. Areas of anatomical and quantitative correlation between NAWM and GM damage were detected. Multiple regression analyses were performed to investigate whether NAWM FA or GM volume of regions correlated with clinical scores independently from the other and from age and gender. In patients, we found 11 brain regions that showed an anatomical correspondence between reduced NAWM FA and GM atrophy; of these, four showed a quantitative correlation (i.e., the right sensory motor region with the adjacent corticospinal tract, the left and right thalamus with the corresponding thalamic radiations and the left insula with the adjacent WM). Either the NAWM FA or the GM volume in each of these regions correlated with disability. These results demonstrate a link between the pathological processes occurring in the NAWM and in the GM in PPMS in specific, clinically relevant brain areas. Longitudinal studies will determine whether the GM atrophy precedes or follows the NAWM damage. The methodology that we described may be useful to investigate other neurological disorders affecting both the WM and the GM.

Thalamic Damage Predicts the Evolution of Primary-Progressive Multiple Sclerosis at 5 Years

“…The role of NAWM and GM involvement in determining overall clinical disability and impairment of selected clinical domains in patients with PPMS is in agreement with the results of recent investigations performed by using different methods of analysis. 34,35 Remarkably, our results are also in line with a postmortem study 36 showing that diffuse NAWM injury and GM demyelination are characteristic hallmarks of PPMS.…”

Combined analysis of grey matter voxel-based morphometry and white matter tract-based spatial statistics in late-life bipolar disorder

“…We therefore conclude that the TBSS analysis of fractional anisotropy was more sensitive than the VBM analysis of grey matter in patients with bipolar disorder. This observation is consistent with the few available combined VBM and TBSS studies of multiple sclerosis 64 and ataxia. 65,66 However, in the absence of a gold standard reference for the morphometric differences between patients with bipolar disorder and healthy controls, we cannot determine which method is more valid in this clinical context.…”

Magnetic resonance imaging correlates of first-episode psychosis in young adult male patients: combined analysis of grey and white matter

“…This observation is consistent with several combined VBM and TBSS studies. 36,37 Correlation between clinical or cognitive measures and grey or white matter data…”