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Utilizing QSM to assess long-term longitudinal susceptibility changes in enhancing multiple sclerosis lesions1Radiology, Tongji Hospital, Tongji Medical College, HUST, Wuhan, China, 2Radiology, Weill Cornell Medical College, New York, NY, United States, 3Mathematics, College of Sciences and Health Professions, Cleveland State University, Cleveland, OH, United States, 4Biomedical Engineering, Cornell University, Ithaca, NY, United States, 5Neurology, Weill Cornell Medical College, New York, NY, United States
Synopsis
We measured the longitudinal susceptibility change of 32 new Gd-enhancing lesions from 19 multiple sclerosis (MS) patients over six years. Lesion susceptibility increased to peak within 1-2 years and was followed by a steady decline. Lesions with QSM rim had an overall higher susceptibility and demonstrated a decay rate that was significantly slower compared to that of lesions without rim.
Introduction
Enhancing multiple sclerosis (MS) lesions identified on post-Gadolinium (Gd) T1w images are representative of breakdown of the blood brain barrier (BBB) and active disease activity. As the BBB closes, lesions transition to the chronic stage; however, a subset of lesions may retain a rim of iron-enriched inflammatory cells, which has been linked to greater tissue damage (1,2). Quantitative susceptibility mapping (QSM) provides accurate in vivo quantification of susceptibility changes related to iron deposition and the potential to identify lesions harboring iron-laden inflammatory cells (3). Identification of different lesion trajectories, as it relates to iron deposition, from the time of enhancement to the chronic lesion stages, is important for identifying potential therapeutic targets (4). The objective of this study was to utilize QSM to assess the longitudinal evolution of susceptibility changes in Gd-enhancing lesions and to determine if lesion trajectories may differ based upon the development of a hyperintense rim on QSM.Methods
Patients were selected from an on-going prospective MRI/clinical database for which annual QSM was collected over the course of six years. Patients were selected for this study if they met the following criteria: 1) had at least 1 new Gd-enhancing MS lesion, 2) had at least 3 longitudinal QSM scans, and 3) the patient’s last MRI was at least one year after the time of Gd enhancement. Lesion age was calculated as the difference (in years) between each scan and the baseline scan. Lesions were identified on the baseline QSM images and overlaid on all subsequent QSM images to obtain lesion susceptibility at each time point. The susceptibility values were measured by referring to adjacent normal appearing white matter (NAWM). Lesions were grouped as rim+ if a rim appeared on QSM image for at least one time point and rim- otherwise. A multilevel regression model with orthogonal time polynomials was used to compare the longitudinal evolution of susceptibility values between rim+ and rim- lesions.Results
32 new Gd-enhancing lesions from 19 MS patients were included in this study, with an average follow-up time of 3.6 years (range 1.1-6.1 years, median 3.2 years). Sixteen lesions (50%) were identified as rim+, wherein the rim appeared at time of enhancement for 13 (81%). Considering all lesions, susceptibility was slightly increased at time of enhancement, demonstrated an evolution that peaked around 1-2 years and then start to decrease over time (Figs.1-3). After controlling for multiple lesions per patient, baseline EDSS and baseline lesion size, there was a significant difference between the longitudinal evolution of rim+ and rim- lesions (p<0.0001). The average susceptibility peak for rim- lesions is -7.60 ppb lower than that for rim+ lesions (p=0.002) and on average, rim- lesions demonstrated a significantly faster decay rate as compared to rim+ lesions (p =0.035) (Fig.3).Discussion
Our results are consistent with an increase in susceptibility related to demyelination and iron deposition in early stages of MS lesions. Lesions with a hyperintense rim on QSM showed a higher level of susceptibility with a much longer retention of elevated QSM values; both of which are consistent with the presence of chronic inflammation. The majority of rim+ of lesions can be identified at the enhancing stage and as this work is expanded, QSM can be utilized to assess factors that influence the duration of retained inflammation among individual lesions. In conclusion, QSM can be utilized to monitor the presence of dynamic changes in iron and inflammation among early stage and chronic MS lesions.Acknowledgements
This work was supported in part from R01NS090464, R01NS104283 and RG-1602-07671.References
1. Absinta M, Sati P, Schindler M, Leibovitch EC, Ohayon J, Wu T, et al. Persistent 7-tesla phase rim predicts poor outcome in new multiple sclerosis patient lesions. The Journal of clinical investigation 2016; 126(7): 2597-609.
2. Yao Y, Nguyen TD, Pandya S, Zhang Y, Hurtado Rua S, Kovanlikaya I, 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 American journal of neuroradiology 2017.
3. Wang Y, Spincemaille P, Liu Z, et al. Clinical quantitative susceptibility mapping (QSM): Biometal imaging and its emerging roles in patient care. J Magn Reson Imaging 2017;46:951-971
4. Chen W, Gauthier SA, Gupta A, et al. Quantitative susceptibility mapping of multiple sclerosis lesions at various ages. Radiology 2014;271:183-192
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