Liu, Z; Pardini, M; Yaldizli, O; Sethi, V; Muhlert, N; Wheeler-Kingshott, CAM; Samson, RS; ... Chard, DT; + view all Liu, Z; Pardini, M; Yaldizli, O; Sethi, V; Muhlert, N; Wheeler-Kingshott, CAM; Samson, RS; Miller, DH; Chard, DT; - view fewer (2015) Magnetisation transfer ratio measures in normal appearing white matter show periventricular gradient abnormalities in multiple sclerosis. Brain , 138 (5) pp. 1239-1246. 10.1093/brain/awv065.

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Abstract

In multiple sclerosis (MS), there is increasing evidence that demyelination, and neuronal damage within and beyond lesions, occurs preferentially in cortical grey matter (GM) next to the outer surface of the brain. It has been suggested that this may be due to the effects of pathology outside the brain parenchyma, in particular meningeal inflammation or through cerebrospinal fluid (CSF) mediated factors. White matter (WM) lesions are often located adjacent to the ventricles of the brain, suggesting the possibility of a similar outside-in pathogenesis, but an investigation of the relationship of periventricular normal-appearing (NA) WM abnormalities with distance from the ventricles has not previously been undertaken. The present study investigates this relationship in vivo using quantitative MR imaging and compares the abnormalities between SPMS and relapsing remitting (RR) MS. Forty-three people with RRMS and 28 with SPMS, and 38 healthy controls, were included in this study. T1-weighted volumetric, magnetisation transfer (MT) and PD/T2-weighted scans were acquired for all subjects. From the MT data, MT ratio (MTR) maps were prepared. WM tissue masks were derived from SPM8 segmentations of the T1-weighted images. NAWM masks were generated by subtracting WM lesions identified on the PD/T2 scan, and a 2 voxel perilesional ring, from the SPM8 derived WM masks. WM was divided in concentric bands, each about 1 mm thick, radiating from the ventricles toward the cortex. The first periventricular band was excluded from analysis to mitigate partial volume effects, and NAWM and lesion MTR values were then computed for the ten bands nearest to the ventricles. Compared with controls, MTR in the NAWM bands was significantly lower in MS. In controls, MTR was highest in the band adjacent to the ventricles and declined with increasing distance from the ventricles. In the MS groups, relative to controls, reductions in MTR were greater in the SPMS compared with RRMS group, and these reductions were greatest next to the ventricles and became smaller with distance from them. WM lesion MTR reductions were also more apparent adjacent to the ventricle and decreased with distance from the ventricles in both the RR and SPMS groups. These findings suggest that in people with MS, and more so in SPMS than RRMS, tissue structural abnormalities in NAWM and WM lesions are greatest near the ventricles. This would be consistent with a CSF or ependymal mediated pathogenesis.

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