Multi-component Driven Equilibrium Single Pulse Observation of T1 and T2 (mcDESPOT) is a whole-brain magnetic resonance relaxation method that allows the evaluation of white matter (WM) myelination by means of measuring the volume fraction of myelin (VFM)¹. Besides providing the prospect to quantify the hidden demyelinating burden of disease in normal appearing tissue² the mean VFM within lesional WM pathology revealed to be the greatest risk factor for the conversion of CIS to clinical definite MS in recent work3. The aim of this work was to observe lesion myelination within the first year of CIS and early MS.

A 1.5 T MR scanner (Sonata, Siemens Healthcare, Germany) and an 8-channel head RF coil were used to derive multi-component T1 and T2 information from sets of Fast Low Angle SHot (FLASH) and True Fast Imaging with Steady State Precession (TrueFISP) data acquired over a range of flip angles at constant TR1. FOV=22cm, matrix=128^2, 1.7mm^3, acquisition time ~13min; FLASH: TE/TR=2.0/5.7ms, α={5,6,7,8,9,11,13,18}°; FISP: TE/TR=1.71/3.42ms, α={9,14,19,24,28,34,41,51,60}°.

Common data post processing involving brain extraction and co-registration of scans were used (SPM/FSL)². VFM maps were calculated from FLASH and TrueFISP data for each subject and time-point using the mcDESPOT theory and processing method1. A semi-automatic method was used to generate binary masks of MS lesions, focal areas of elevated signal intensity in FLAIR data².

In four steps the new algorithm Automatic Follow-up of Individual Lesion (AFIL) found corresponding lesions in time-series. (1) The function bwlabeln (MATLAB Image Processing Toolbox) found related lesion in the masks and labeled them (Fig.1), (2) determined intersections in space with lesions of prior time points. (3) distinguished new lesions without intersections with a previous time-point. (4) obtained a global label to be observed in a time-series. Lesion volumes and mean VFM were quantified. The threshold of the lesion mean VFM change ≤ ± 0,01 was used to define single lesion categories as [A] dynamic, [B] demyelinating, [C] remyelinating (>+0,01), and, [D] stable. The normal WM mean VFM was obtained from healthy controls.In total n=137 lesions were evaluated longitudinally. A dynamic in decrease and increase in VFM was found in 56% of the lesions. Progressive demyelination was found in 25% and remyelination in 14%. A minor number of lesions (5%) showed stable myelination over all time-points. In contrast to FLAIR, the myelin-sensitive VFM revealed different prospects in lesion development (Fig.2). Demyelinating lesions had 10% median loss, (IQR=13%) and dynamic lesions -4% (IQR=17%) of VFM whereas remyelinating lesion revealed a regain of 27% (IQR=25%) in VFM.Our findings demonstrate an in vivo measurable highly dynamic individual lesion myelination status in CIS and subsequent early MS. The new method facilitates to quantify lesion formation and to observe damage and reparative mechanism distribution in individual patients. This may allow depicting phenotypes of the extent of myelin loss and its dynamic features to select patients for individualized therapeutic approaches and to monitor their treatment response.