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Chronic MS lesions with hyperintense appearance on QSM demonstrate more myelin damage and are long-lasting
Shun Zhang1,2, Thanh D. Nguyen2, Yi Wang2,3, and Susan A. Gauthier4

1Radiology, 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 assessed longitudinal QSM and MWF changes in 307 chronic MS lesions from 41 patients over four years. Lesions were stratified into three groups: hyperintense rim on QSM (rim+), no rim (rim-) and isointense on QSM (QSM-). Rim+ lesions were found to have the lowest MWF. QSM lesions showed a decreasing trend while MWF remains relatively stable over the same period.

Introduction

Studies have demonstrated that chronic active multiple sclerosis (MS) lesions often have a rim of iron-containing activated microglia and macrophages1. Quantitative susceptibility mapping (QSM) can be used to identify a subset of lesions more likely to have retained iron at the rim2. In a recent longitudinal QSM study, rim lesions have been associated with greater myelin damage as measured by myelin water fraction (MWF)2. However, longitudinal MWF measurements were not available. In this study, we quantified and compared the differences in longitudinal changes of both QSM and MWF over a 4-year period among lesions with QSM hyperintense rim and other chronic lesions.

Methods

Forty-one MS patients were selected from an on-going prospective MRI/clinical database for which annual QSM and MWF (using FAST-T23) was collected over the course of 4 years. 307 chronic lesions were identified and lesion area with its contralateral normal appearing white matter (NAWM) were manually segmented. MS lesions were classified as 3 groups according to its appearance at baseline: QSM hyperintense with rim appearance (rim+, n=59, 19%), QSM hyperintense without rim appearance (rim-, n=128, 42%), and QSM isointense lesions (QSM-, n=120, 39%). Lesion susceptibility was referenced to contralateral NAWM.

Results

At baseline, QSM rim+ positive lesions had higher susceptibility (23.62 ± 18.45 ppb) compared to both rim- (11.33 ± 12.73 ppb) and QSM- lesions (-0.41 ± 9.73 ppb). Rim+ lesions had the lowest MWF (6.76 ± 2.57%), while the highest MWF was found in QSM- lesions (9.70 ± 1.87%), p<0.001. All three lesion groups had significantly lower MWF than NAWM (11.92 ± 1.73%) (all p values<0.001). There was a trend of decreasing susceptibility in rim+ (-6.27 ± 9.77 ppb, p<0.001) and rim- lesions (-7.23 ± 10.48 ppb, p<0.001) while QSM- lesions remained stable (-0.80 ± 10.86 ppb, p=0.42) (Figs. 1&3). MWF remained stable (within the range of reproducibility3, 4) for all three lesion groups (Figs. 2&3). ANOVA analysis for comparing QSM and MWF among the three groups revealed significant differences at each of the 4 time points (all p values<0.005).

Discussion

QSM rim+ lesions have more myelin damage consistent with chronic active lesions having more tissue damage. As this work is expanded, our goal is to improve the resolution of MWF to explore ongoing myelin damage at the edge of QSM rim+ lesions. In conclusion, QSM and MWF are useful to identify lesions with more tissue damage and QSM can be utilized to monitor pathologic iron deposition.

Acknowledgements

This work was supported in part from R01NS090464, R01NS104283 and RG-1602-07671.

References

1. Absinta M, Sati P, Schindler M, et al. Persistent 7-tesla phase rim predicts poor outcome in new multiple sclerosis patient lesions. J Clin Invest 2016;126:2597-2609

2. Yao Y, Nguyen TD, Pandya S, et al. Combining Quantitative Susceptibility Mapping with Automatic Zero Reference (QSM0) and Myelin Water Fraction Imaging to Quantify Iron-Related Myelin Damage in Chronic Active MS Lesions. AJNR Am J Neuroradiol 2018;39:303-310

3. Nguyen TD, Deh K, Monohan E, et al. Feasibility and reproducibility of whole brain myelin water mapping in 4 minutes using fast acquisition with spiral trajectory and adiabatic T2prep (FAST-T2) at 3T. Magn Reson Med 2016;76:456-465

4. Vargas WS, Monohan E, Pandya S, et al. Measuring longitudinal myelin water fraction in new multiple sclerosis lesions. Neuroimage Clin 2015;9:369-375

Figures

Figure 1. An example of a 47-year-old year male with relapsing-remitting MS with serial QSM and MWF mapping at years 1, 2, and 4. Three chronic MS lesions demonstrated a hyperintensity on QSM at baseline, which gradually disappeared over time. On MWF images, the lesions showed low but relatively stable MWF values.

Figure 2. Three representive MS lesions for QSM rim+, QSM rim- and QSM- group. Rim+ lesion had the lowest MWF indicating greater tissue damage.

Figure 3. Temporal evolution of QSM and MWF in chronic MS lesions among QSM rim+, QSM rim-, and QSM- groups. The susceptibility of rim+ and rim- lesions showed a decreasing trend with time, while QSM- lesions remained stable. Rim+ lesions had lower MWF than rim- and QSM- lesions, and all three lesion groups had lower MWF compared to contralateral NAWM.

Proc. Intl. Soc. Mag. Reson. Med. 27 (2019)
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