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Concurrent remyelination and susceptibility increase in new active MS lesions indicate early iron accrual1Radiology, Tongji Hospital, Tongji Medical College, HUST, Wuhan, China, 2Radiology, Weill Cornell Medical College, New York, NY, United States, 3Biomedical Engineering, Cornell University, Ithaca, NY, United States, 4Neurology, Weill Cornell Medical College, New York, NY, United States
Synopsis
We reported initial results of an ongoing longitudinal study of new enhancing lesions using quantitative MRI including QSM, MWF and DTI. MS patients were followed five times during the first three months of lesion formation. We found a subset of lesions in which QSM rises rapidly and simultaneously with MWF and FA measurements, suggesting increasing iron accumulation within this period.
Introduction
Iron plays an important role in the pathogenesis and progression of multiple sclerosis (MS) lesions1, 2. Iron mediated inflammation and its association with myelin repair in chronic lesions with rim appearance on MRI has attracted significant research interest recently3-5. However, there is relatively limited knowledge on the interaction between iron and myelin changes during the first few weeks and months of a new acute lesion following their first appearance on Gadolinium enhancing T1w image. Our objective was to capture longitudinal changes of new enhancing MS lesions on quantitative MRI of myelin and iron, with five scans during the first three months and seven scans within the first year of lesion formation.Methods
Five MS patients were imaged on Siemens 3T scanners as part of an ongoing longitudinal research study. The imaging protocol consisted of conventional T1w (before and after Gadolinium administration), T2w and FLAIR sequences, as well as quantitative MRI including FAST-T2 MWF mapping, quantitative susceptibility mapping (QSM) and diffusion tensor imaging (DTI). Maps of T1 and intra/extracellular water T2 (ieT2, markers of edema) were also obtained from FAST-T2 data. Following the baseline scan defined as the time a new lesion first appeared on the Gadolinium-enhancing image, follow-up MRIs were performed at 2 week (w), 4w, 1.5 month (m), 2m, 3m, 6m and 12 m. Only subjects with serial MRI up to 6 months were included in the data analysis. All images were co-registered to QSM space using FSL package. Lesion masks were traced by a neuroradiologist on the co-registered T2w image and then overlaid on parametric maps including QSM, MWF, T1, ieT2, fractional anisotropy (FA), and mean diffusivity (MD). Contralateral NAWM region of interest of similar size was also obtained for reference.Results
Ten new enhancing MS lesions were included in the analysis. Lesion changes can be broadly divided into two group with markedly different temporal dynamics. In the first group (n=6, Fig.1), a sharp parallel increase in both QSM and myelin markers including MWF and FA was seen within the first 2-3 months. There was a simultaneous resolving of edema indicated by the decrease in lesion T1 and ieT2. After this short period of rapid changes indicating tissue recovery, these parameters tend to reach a plateau characterized by much slower lesion dynamics. It is worth noting that there is still a marked difference between recovered lesion and the contralateral NAWM (Fig.1). Figure 2 shows lesion behavior of the second smaller group (n=4), which shows relatively stable QSM, MWF and DTI parameters over the observed one year period after Gd-enhancement.Discussion
This was the first study to capture longitudinal QSM and MWF changes in new acute Gd-enhancing lesions within the first year of their formation. We found a subset of lesions in which QSM rises rapidly and simultaneously with MWF and FA measurements in the first 2-3 months. The increase of QSM has been reported6, 7, part of which is attributed to the breakdown and removal of myelin debris by macrophages in the first several weeks8. The parallel increase of QSM, MWF, and FA parameters observed in our preliminary results provides strong evidence that the rise in QSM is caused by accumulation of paramagnetic iron and not by demyelination. The association of this iron increase with myelin repair as the lesion ages will help elucidate the role of iron in MS pathology.Acknowledgements
This work was supported in part from R01NS090464, R01NS104283 and RG-1602-07671.References
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