Abstract

PurposeTo assess neuroprotection and remyelination in Multiple Sclerosis (MS), we applied a more robust myelin water imaging (MWI) processing technique, including spatial priors into image reconstruction, which allows for lower SNR, less averages and shorter acquisition times. We sought to evaluate this technique in MS-patients and healthy controls (HC).Materials and MethodsSeventeen MS-patients and 14 age-matched HCs received a 3T Magnetic Resonance Imaging (MRI) examination including MWI (8 slices, 12 minutes acquisition time), T2w and T1mprage pre and post gadolinium (GD) administration. Black holes (BH), contrast enhancing lesions (CEL) and T2 lesions were marked and registered to MWI. Additionally, regions of interest (ROI) were defined in the frontal, parietal and occipital normal appearing white matter (NAWM)/white matter (WM), the corticospinal tract (CST), the splenium (SCC) and genu (GCC) of the corpus callosum in patients and HCs. Mean values of myelin water fraction (MWF) were determined for each ROI.ResultsSignificant differences (p≤0.05) of the MWF were found in all three different MS-lesion types (BH, CEL, T2 lesions), compared to the WM of HCs. The mean MWF values among the different lesion types were significantly differing from each other. Comparing MS-patients vs. HCs, we found a significant (p≤0.05) difference of the MWF in all measured ROIs except of GCC and SCC. The mean reduction of MWF in the NAWM of MS-patients compared to HCs was 37%. No age, sex, disability score and disease duration dependency was found for the NAWM MWF.ConclusionMWF measures were in line with previous studies and lesions were clearly visible in MWI. MWI allows for quantitative assessment of NAWM and lesions in MS, which could be used as an additional sensitive imaging endpoint for larger MS studies. Measurements of the MWF also differ between patients and healthy controls.

Highlights

  • Multiple sclerosis (MS) is the most common chronic central nervous system (CNS) disorder of young adults, leading to demyelination and axonal damage [1,2]

  • Significant differences (p0.05) of the myelin water fraction (MWF) were found in all three different MS-lesion types (BH, contrast enhancing lesions (CEL), T2 lesions), compared to the white matter (WM) of healthy controls (HC)

  • The mean reduction of MWF in the normal appearing white matter (NAWM) of MS-patients compared to HCs was 37%

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Summary

Introduction

Multiple sclerosis (MS) is the most common chronic central nervous system (CNS) disorder of young adults, leading to demyelination and axonal damage [1,2]. Specific imaging biomarkers are urgently required for early detection of neuroprotective therapy effects and remyelination processes in MS [3]. Imaging markers such as discrete inflammatory lesions in T2-weighted magnetic resonance imaging (MRI) and contrast enhancing lesions in T1-weighted MRI have become biomarkers for the measurement of treatment effects targeted at multifocal inflammatory demyelination [4,5]. Myelin water imaging (MWI) is an imaging technique primarily based on multi echo spin echo (MESE) T2 relaxometry, which may be less sensitive to concomitant pathological processes such as inflammation [10]. The term myelin water fraction (MWF) has been established to be a potential marker for myelin integrity [11]

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