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 ( , ). 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. 1. Introduction Multiple sclerosis (MS) is the most common autoimmune disease of the central nervous system (CNS), and it is characterised by inflammation, demyelination and degenerative changes [1]. The identification of surrogate markers reflecting pathophysiological events in the CNS and correlating with clinical outcomes is highly needed for refining diagnostics and developing therapeutic approaches in patients with MS [2, 3]. Magnetic resonance imaging (MRI) is the most valuable paraclinical tool for monitoring the disease process in vivo, but the correlations between clinical and conventional imaging measures detected thus far have been generally suboptimal [4]. This phenomenon is most likely explained by the limitations of expanded disability status scale (EDSS) scoring and the ability of conventional MRI to reflect changes in the CNS consistent with different manifestations of MS [4, 5]. Recent neuropathological studies in MS have shown widespread tissue damage in both normal-appearing white matter (NAWM) and grey matter (NAGM) tissues [6] that are not detected by conventional MRI [7]. Nonconventional MRI approaches such as diffusion tensor imaging (DTI) allow for further examination of brain tissues in vivo. DTI utilises the orientation-dependent diffusion property of water molecules within the CNS and provides unique information on the pathological processes that reflect the microstructural damage in brain [8]. Tissue
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