Background

Magnetic resonance imaging (MRI) is applied to monitor multiple sclerosis (MS) evolution and to evaluate disease progression. Unfortunately, conventional MRI is non-specific for myelin. Therefore, the in vivo whole brain myelin imaging technique Multi-Component Driven Equilibrium Single Pulse Observation of T1 and T2 (mcDESPOT) [1], that allows the assessment of relative myelination by measuring the myelin water fraction (MWF) [2], is expected to quantify myelination of the entire brain and thus assesses intra- and interindividual differences.

Objectives

The aim of this study was to explore MWF as a biomarker to analyse myelination differences in relapsing remitting (RRMS) and secondary progressive (SPMS) MS patients. In this study MWF was retrieved in WM of healthy controls (HC), normal appearing WM (NAWM) and T2 lesions (T2L) to parse differences in global and focal myelin loss in RRMS and SPMS.

Methods

A 1.5T MR scanner (Siemens Sonata) and an 8-channel head RF coil was used to derive 3D-fluid attenuated inversion recovery (FLAIR) images of n=112 RRMS (EDSS_mean=2.7±1.2) and n=24 SPMS (EDSS_mean=5.4±1.4) patients. WM, NAWM and T2L were segmented into binary masks. Common data post processing involving brain extraction and co-registration of scans was used (FSL/ANTs)[3,4]. MWF maps were derived using the established mcDESPOT processing method [1]. A matched control group (n=63) was acquired. Differences in MWF of healthy controls, RRMS and SPMS were determined with a wilcoxon rank sum test (p < 0.05).

A 1.5T MR scanner (Siemens Magnetom Sonata equipped with a 8-channel radio-frequency coil was used and sets of 3DFluid-Attenuated Inversion Recovery (FLAIR), Spoiled Gradient Recalled (SPGR) and Balanced Steady- State Free-Precession (bSSFP) images were

obtained. According to the mcDESPOT protocol SPGR and bSSFP scans were acquired over a range of flip angles at constant echo time (TE) and repetition time (TR) using the following specifications: field of view (FOV) = 22 cm, slice thickness = 1.7 mm; SPGR: TE/TR = 2.0/ 5.7 ms, flip angle (α)= [5, 6, 7, 8, 9, 11, 13, 18]°; bSSFP: TE/ TR = 1.71/3.42 ms, α = [9, 14, 19, 24, 28, 34, 41, 51, 60]°; acquisition time ~13min.

Results

The MWF in WM of HC was (MWF_{mean, SD}=0.230 ± 0.007) versus MWF in NAWM of RRMS (MWF_{mean, SD}=0.224 ± 0.01) and SPMS (MWF_{mean, SD}=0.213 ± 0.012) patients. Significant MWF differences (p <0.05) were found for HC vs. MS patients. Mean T2L volume was significantly higher in SPMS patients (T2L volume_RRMS= 4,3ml±6,4ml vs. T2L volume_SPMS= 16.8ml±14.9ml). MWF in T2L of RRMS patients was MWF_{mean, SD} =0.117 ± 0.03 ranging from MWF_min=0.032 to MWF_max = 0.201 and for SPMS patients MWF_{mean, SD} =0.130 ± 0.02 ranging from MWF_min=0.088 to MWX_max = 0.177. Significant MWF differences were found for T2L of the RRMS vs. SPMS group.

Conclusions

Our findings demonstrate varying degrees of myelination within T2L in MS patients, indicating a heterogeneous MWF loss in RRMS and SPMS patients.