Synopsis

To track evolution of multiple sclerosis (MS) lesions, 9 patients underwent gradient-echo-T2* and quantitative susceptibility mapping on 7T MR system at baseline and at follow-up period (mean duration=2.4years). Majority of lesions were non-iron laden at baseline and most of them remained unchanged in size, morphology and susceptibility patterns. Some of these lesions accumulated iron deposition on follow-up. A minority of iron-laden lesions underwent redistribution of iron content. Small increase in lesion count was observed at follow-up. Interestingly, majority of these lesions were iron-enriched. This study may provide insights into pathophysiological features of MS lesions during the course of disease evolution.

Purpose: In a previous cross-sectional study,¹ we described four morphologically distinct patterns of multiple sclerosis (MS) lesions using multi-contrast MRI at 7T. Two patterns (A and B) were non-iron laden, and the other two (C and D) were iron-enriched as shown in Figure 1. However, underlying pathophysiology of these lesions is dynamic and it changes over time during the course of disease.^2,3 Moreover, the presence and spatial distribution of iron in MS lesions is also expected to vary as lesions form and evolve. Therefore, in this study, we will provide the longitudinal follow-up data involving patients with MS and the objective of the present study was to track the evolution of MS lesions over time on 7T MRI.

Methods: A cohort of nine patients with definite MS underwent flow compensated and high-resolution (in plane resolution: 210x210μm²) 3D-susceptibility weighted imaging (SWI) and axial 2D-gradient-echo (GRE)-T2*-weighted imaging on 7T MRI at baseline and at follow-up period (mean duration: 2.40 ± 0.57 years, range: 2.01-3.83 years). SWI and the susceptibility mapping algorithm developed by Haacke et al.^4,5 was used to reconstruct quantitative susceptibility mapping (QSM) from 3D-SWI data. All MS lesions were analyzed side by side on axial GRE-T2*, 3D-SWI, and QSM images. The following morphologic imaging characteristics were recorded : 1) location; 2) size; 3) total count; 4) lesion-vessel relationship; 5) differential signal intensity within the lesions; and 6) presence of a peripheral rim. Lesions were classified as "iron-laden" if they demonstrated hypointensity on T2*-weighted images and/or SWI and hyperintensity on QSM. Lesions were considered "non-iron-laden" if they were hyperintense on T2* and isointense or hyperintense on QSM.

Results: We report a comparison of salient features of MS lesions at baseline and at follow-up.

Lesion Characterization at Baseline

Lesion Count: A total of 191 lesions were observed at baseline. Lesion-vessel relationship: Central-vein was identified in 139 (73%) lesions. Percentage of lesions with a venule was similar for the different pattern (70% pattern A and 69% of pattern C). However, percentage of lesions with a venule differed by location: highest in periventricular lesions (85%), followed by subcortical (70%), corpus callosum (67%) and lowest in juxtocortical (46%) lesions. Lesion Pattern: Majority of lesions 157/191 (82%) were non-iron laden.

Lesion Characterization at Follow-up

Lesion Count: A total of 204 lesions were observed at follow-up period, a miniscule (7%) increase of lesion number from baseline. Lesion-vessel relationship: Central venule within a lesion was observed in 129/139 (91%) lesions, which contained a venule at baseline (Fig. 2). Lesion Pattern: Of the 34 lesions that were iron-laden at baseline, all but one remained iron-laden at follow-up (Fig. 3). Pattern switch was observed in only 6 lesions (3%) from 3 patients. Of these 6 lesions, there was an apparent increase in iron content [pattern A (non-iron laden) to pattern C (iron laden)] in 3 lesions (Fig. 4). In one lesion, there was loss of iron content (pattern C to pattern A) and in other 2 lesions, there was redistribution of iron content from nodular to ring-like appearance (pattern C to pattern D). Interestingly, although only 33% of all follow-up lesions were iron-laden, 11/13 (85%) of new lesions, which were not seen at baseline, were of iron-laden (Fig. 5).

Discussion: A vast majority of lesions that were non-iron laden at baseline remained non-iron enriched on a follow-up period of ~2.4 years. Most of these lesions showed no obvious changes in radiological features such as intensity, size, and morphology through the course of the follow-up. We believe that these lesions were in chronic inactive stage of their evolution characterized by varying degrees of demyelination, edema, micronecrosis, and gliosis.⁶ It has been reported that not all MS lesions have iron deposition⁷ and not all macrophages or microglia contain iron,⁸ which indicates that iron deposition may vary among individual lesions based on their age and inflammatory status. Previous correlative MRI and histochemical studies^8,9 have shown that iron deposits were present in a subset of chronic, demyelinating active MS lesions. In consistent with prior reports¹⁰ with shorter follow-up, most of iron leaden lesions at baseline exhibited iron content on follow-up in our study. Interestingly, most of new lesions were iron enriched. Rapid iron accumulation seems to be a hallmark of the MS lesion formation, which is different than the slow change of iron after lesion formation.¹¹ A very recent study¹² also demonstrated that MS lesions with iron rim grow very slowly.

Conclusion: Our longitudinal study provides insights into the morphological and iron related pathophysiological features of MS lesions during the course of disease evolution.

Acknowledgements

References

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