Diffusion Tensor Imaging in NAWM and NADGM in MS and CIS: Association with Candidate Biomarkers in Sera

Abstract

The aim of this study was to evaluate diffusion tensor imaging (DTI) indices in the corpus callosum and pyramidal tract in normal-appearing white matter (NAWM) and the caudate nucleus and thalamus in deep grey matter (NADGM) in all MS subtypes and clinically isolated syndrome (CIS). Furthermore, it was determined whether these metrics are associated with clinical measures and the serum levels of candidate immune biomarkers. Apparent diffusion coefficients (ADC) values were significantly higher than in controls in all six studied NAWM regions in SPMS, 4/6 regions in RRMS and PPMS and 2/6 regions in CIS. In contrast, decreased fractional anisotropy (FA) values in comparison to controls were detected in 2/6 NAWM regions in SPMS and 1/6 in RRMS and PPMS. In RRMS, the level of neurological disability correlated with thalamic FA values (r = 0.479, P = 0.004). In chronic progressive subtypes and CIS, ADC values of NAWM and NADGM were associated with the levels of MIF, sFas, and sTNF- α . Our data indicate that DTI may be useful in detecting pathological changes in NAWM and NADGM in MS patients and that these changes are related to neurological disability.

Figure 1

Region-of-interest (ROI) placement on axial FA colour maps. The posterior limb of the internal capsule (1, 2), the splenium (3), and the genu (4) of the corpus callosum (a); the posterior corona radiata anterior (1, 2) and posterior (3, 4) (b); the centrum semiovale anterior (c); and the caudate nucleus (1, 2) and the thalamus (3, 4) (d). Colours indicate the directions of fibre tracts (red, transverse; blue, craniocaudal; green, anterior-posterior). The circular ROIs were transferred from the corresponding B ₀ image, and their sizes have been adjusted to avoid any visible lesions. The size of the ROIs ranged from 2 to 33 pixels (6–106.5 mm²; pixel size 1.8∗1.8 mm²) depending on the size of the brain structure. This figure is a representative analysis from an SPMS patient.

Figure 2

ADC and FA values in different brain regions of multiple sclerosis (MS) subtypes, clinically isolated syndrome (CIS), and healthy controls (HC). The length of the box represents the interquartile range, which includes the middle 50% of the values. The line through the middle of each box represents the median. The error bars show the minimum and maximum values (range). RRMS, relapsing remitting MS; SPMS, secondary progressive MS; PPMS, primary progressive MS; ADC, apparent diffusion coefficient; FA, fractional anisotropy. Reported P values were calculated using the univariate analysis of variance with age as covariate followed by post hoc multiple pairwise comparisons with Bonferroni correction. **P < 0.0006 (n = 80), *P < 0.005 (n = 10) when compared to HC. ^## P < 0.0006 (n = 80), ^# P < 0.005 (n = 10) when compared to CIS. ^¤ P < 0.005  (n = 80) in comparison to RRMS. ^∅ P < 0.005 (n = 80) in comparison to PPMS.

Figure 3

Correlations between DTI indices and clinical and immunological parameters in MS and CIS. Statistically significant correlations were found between the EDSS score and FA values for the thalamus in RRMS (a), disease duration and ADC values for the caudate nucleus in RRMS (b), the levels of MIF and the ADC values for the corona radiata posterior in SPMS (c), the levels of TNF-α and the ADC values for the thalamus in PPMS (d), and the levels of Fas and the ADC values for the internal capsule in CIS (e).