Multi-parametric quantitative MRI of normal appearing white matter in multiple sclerosis, and the effect of disease activity on T2

Abstract

White matter (WM) lesions with a distinct lesion-tissue contrast are the main radiological hallmark of multiple sclerosis (MS) in standard magnetic resonance imaging (MRI). Pathological WM changes beyond lesion development lack suitable contrasts, rendering the investigation of normal appearing WM (NAWM) more challenging. In this study, repeat quantitative MRI (qMRI) was collected in 9 relapsing remitting MS patients with mild disease over nine months. The relaxation times T1 and T2, the proton density (PD), and the magnetization transfer ratio (MTR) were analysed in the NAWM. For each parameter, both the mean value and the standard deviation were determined across large NAWM regions. The resulting 8-dimensional multi-parameter space includes parameter non-uniformities as additional descriptors of NAWM inhomogeneity. The goals of the study were to investigate (1) which of the eight parameters differ significantly between NAWM and normal WM, (2) if parameter time courses differ between patients with and without radiological disease activity, and (3) if a suitable biomarker can be derived from the multi-parameter space, allowing for NAWM characterization and differentiation from controls. On a group level, all parameters investigated except mean T1 values were significantly affected in MS NAWM. Group classification accuracy using a multi-parametric support vector machine approach in NAWM was 66.7 %. In addition, mean T2 values increased significantly with time for patients with radiological disease activity, but not for patients without radiological activity. In conclusion, our data demonstrate the potential of qMRI for investigating MS pathology in NAWM. T2 measurements in NAWM may enable monitoring of disease activity outside of overt lesions.

Longitudinal quantitative MRI assessment of cortical damage in multiple sclerosis: A pilot study

“…These patients were scored on the Expanded Disability Status Scale (EDSS) before the first scan . The patient pool comprised participants who had previously been included in cross‐sectional analyses, and we also used data obtained from a previous study into white matter …”

“…Previous studies have shown the value of qMRI for assessing tissue damage in MS: A study into WM pathology has demonstrated changes in tissue parameters in accordance with inflammatory activity . In the cortex, a region of interest (ROI) analysis showed that cortical T 1 prolongation and PD increase are present in early MS, indicating cortical damage .…”

“…3 Previous studies have shown the value of qMRI for assessing tissue damage in MS: A study into WM pathology has demonstrated changes in tissue parameters in accordance with inflammatory activity. 4 In the cortex, a region of interest (ROI) analysis showed that cortical T 1 prolongation and PD increase are present in early MS, indicating cortical damage. 5 A separate study confirmed a relationship between cortical T 1 and the degree of disability in a relapsingremitting MS (RRMS) patient group, covering a range of disability severity and disease duration.…”

“…14 The patient pool comprised participants who had previously been included in cross-sectional analyses, [5][6][7]15 and we also used data obtained from a previous study into white matter. 4 Written informed consent was given, and this study was approved by the Ethics Committee of the State Medical Association of Rhineland-Palatine. The study has been conducted according to the principles expressed in the Declaration of Helsinki.…”

Metabolomics approaches in experimental allergic encephalomyelitis

“…MR imaging, particularly using multiparametric quantitative techniques (T 1 , T 2 and T 2 * relaxation time measurements, diffusion and magnetization transfer ratio measurements), and MR spectroscopy have been widely used to explain the disease's physiopathology mechanisms including those of observed in the normal appearing white matter (Reitz et al, 2016). In recent years, NMR or mass spectrometry metabolomics, has been used to investigate the metabolite changes in only cerebrospinal fluid which reflects the tissue inflammation associated with EAE (Smolinska et al, 2011;Blanchet et al, 2011;Smolinska et al, 2012;Noga et al, 2012;Lutz et al, 2013;Gebregiworgis et al, 2013;Mangalam et al, 2013;Coulier et al, 2013;Cocco et al, 2015;Dickens et al, 2015;Poisson et al, 2015) or MS (Sinclair et al, 2010;Lutz et al, 2007;Villostada et al, 2017;Bhargava and Calabresi, 2016;Pieragostino et al, 2015;Dickens et al, 2014;Reinke et al, 2014;Vingara et al, 2013;Moussalieh et al, 2014).…”