0057
Closer look at Multiple Sclerosis lesions: an initial result of Positive and Negative Magnetic Susceptibility Separation
Jinhee Jang1, Hyeong-geol Shin2, Yoonho Nam1,3, Jingu Lee2, Jongho Lee2, and Woojun Kim4
1Radiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea, 2Department of Electrical and Computer Engineering, Seoul National University, Seoul, Republic of Korea, 3Radiology, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea, 4Neurology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
1Radiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea, 2Department of Electrical and Computer Engineering, Seoul National University, Seoul, Republic of Korea, 3Radiology, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea, 4Neurology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
Synopsis
While susceptibility contrast gives details for MS lesions, two major changes – iron deposition and de-myelination had same contribution on QSM, increasing bulk magnetic susceptibility. In this work, we applied separation of positive and negative sources in clinical MS patients, and had a closer look of in-vivo MS lesions. We demonstrate variable appearances of MS lesions on separation maps as well as conventional imaging and QSM, and complex distribution and dynamic changes of positive (i.e. iron) and negative (i.e. myelin) in MS lesions, in cross-sectional and longitudinal observations.
Background
Multiple sclerosis (MS) is a neuro-inflammatory disease with progressive clinical course. MRI has been a major tool for monitoring disease extent, activity and treatment response. As MRI has excellent sensitivity to MS lesions, MR appearance of MS lesions are variable, resulting in relatively low specificity. It is based on the histopathological variability of MS lesions [1]. Hence, specific MR contrast is needed that reflects the histopathological characteristics of the MR lesions.MR images using susceptibility contrast, including phase images and quantitative susceptibility mapping (QSM), has been one of the new MR techniques to characterize MS lesion [2]. This popularity is related to that iron and myelin, those show dynamic changes in MS lesions, have good magnetic susceptibility contrast (Figure 1A). One caveat is that while the major changes of them, deposition of paramagnetic iron and loss of diamagnetic myelin could occur simultaneously, both of those changes have the same contribution to magnetic susceptibility (Figure 1B). Hence, current MR approach, including QSM cannot differentiate or separate those pathological changes.
Recently, Lee et al [3] proposed a method that enables separation of positive and negative sources in QSM. The magnetic susceptibility source separation can provide surrogates for distribution of iron (i.e., positive susceptibility) and myelin (i.e., negative susceptibility), respectively. This could be a tailored approach to assess details of MS lesions as an in vivo histological analytic tool [4]. In this work, we applied the proposed method in clinical MRI of MS patients, and evaluate findings of separate maps in variable MS lesions.
Methods
From 10 MS patients (all RRMS types) and their 21 MR scans were analyzed in this study. MRI were done as a part of clinical processes, such as diagnostic work-up or follow-up. Diagnosis was done by an experienced neurologist who was specialized to MS.MR parameters
MRI scan was done using clinical 3T MRI and 32 channel coil with following parameters: FOV 216 x 216 x 144 mm3, voxel size 0.5 x 0.5 x 2 mm3, TR 20 ms, TE 5.8 to 36.7 ms with echo spacing of 6.2 ms, flip angle 17°. Parameters of 3D T2-weighted TSE was as follows: FOV 240 X 240 X 175 MM3, voxel size 1 X 1 X 1 mm3 , TR/TE 2500/300 ms, ETL 135.
Magnetic susceptibility source separation and QSM processing
The magnetic susceptibility source separation algorithm divides positive and negative susceptibility source by using magnitude information (R2’) in addition to phase information used in previous QSM processing [3]. To estimate whole brain R2’ (=R2*-R2) map in clinically feasible scan time, T2-weighted images (3D TSE) are transformed into R2 images by using a linear model: R2 = alpha * (log(ITSE/max(ITSE))). The linear coefficient alpha was determined by linear regression between log(ITSE/max(ITSE)) map and conventional R2 map estimated from multi-echo spin echo sequence. R2* maps are acquired by fitting an exponential fit to multi-echo gradient echo signal. Finally, separated mapping of positive and negative sources were obtained and (χpos And χneg maps, respectively). From frequency estimation using iHARPERELLA [5], QSM calculation was done from iLSQR method [6].
Results
From 10 patients (5 male and 5 female, mean age 32.1 ± 8.3 year old), total of 161 lesions were analyzed (16.1 ± 6.7 lesions/patients). Mean disease duration was 55.4 ± 32.4 months.About 3/4 (124/161, 77.0 %) of MS lesions were paramagnetic on QSM. Among them, 110 (88.7%) lesions showed increased positive source on χpos maps, and 122 lesions (98.4%) showed loss of negative source on χneg maps (Figure 2).
Interestingly, details of susceptibility changes differ between QSM and separation maps (Figure 3a). Fourteen paramagnetic lesions showed loss on χneg maps only, suggesting paramagnetic susceptibility is mainly due to demyelination, not the iron deposition (Figure 3b). In 22 lesions without susceptibility changes on QSM, 2 lesions (10.8%) showed increased paramagnetic contribution on χpos, and about half of the lesions (12/22) showed decreased contribution of diamagnetic on χneg.
In total, 27 lesions (16.8%) showed changes during follow-ups. For lesions were newly noted, and 5 lesions showed contrast-enhancement changes. Two lesions showed increased size, while 4 lesions showed decreased size. Interestingly, 11 lesions showed changes on χpos or χneg (Figure 4). Specifically, 8 lesions showed decreased changes on χneg, while 3 lesions showed increased size or degree of defect on χneg.
Discussion
In this work, we explored the clinical value of separated susceptibility mapping in MS lesions characterization and analysis. Proposed methods were clearly demonstrated pathological changes of MS lesions, those were well correlated with variable histopathological changes of MS plaques [1,2]. We found that most MS lesions have increased positive sources and decreased negative sources simultaneously. Each of them was associated with iron deposition and demyelination, respectively. Also, separation maps showed details of longitudinal changes of MS lesions, which cannot be evaluated using conventional methods. This suggested potential of separation maps as an in-vivo tool to observe MR lesions characters and their changes.Acknowledgements
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2017R1D1A1B03033829) and the Catholic Medical Center Research Foundation made in the program year of 2018.References
[1]. Ludwin SK. The pathogenesis of multiple sclerosis: relating human pathology to experimental studies. J Neuropathol Exp Neurol. 2006;65(4):305-18.
[2] Absinta M, Sati P, Gaitan MI, Maggi P, Cortese IC, Filippi M, et al. Seven-tesla phase imaging of acute multiple sclerosis lesions: a new window into the inflammatory process. Annals of neurology. 2013;74(5):669-78.
[3] Lee, J., Nam, YH., Choi, JY., Shin, H., Hwang, T., and Lee, J. (2017), Separating positive and negative susceptibility sources in QSM, Proc. Intl. Soc. Mag. Reson. Med., 25, 0751.
[4] Lee, J., Hwang, T., Nam, Y., Jang, J., Kim, W., Oh, S-H., Fukunaga, M., Lee, J. (2018), Applications of magnetic susceptibility source separation: multiple sclerosis lesions and line of Gennari, Proc. Intl. Soc. Mag. Reson. Med., 26, 2207
[5] Li, W., Avram, A. V., Wu, B., Xiao, X., & Liu, C. (2014). Integrated Laplacian‐based phase unwrapping and background phase removal for quantitative susceptibility mapping. NMR in Biomedicine, 27(2), 219-227.
[6] Li W, Wang N, Yu F, et al. A method for estimating and removing streaking artifacts in quantitative susceptibility mapping. Neuroimage 2015;108:111-122
Figures
QSM demonstrates bulk susceptibilities of certain area or tissue (A), which enables QSM as an in-vivo analysis tool for specific sources with good magnetic susceptibility. While iron and myelin are important susceptibility contrast sources in MS lesions, iron deposition and demyelination occur simultaneously. This limits the value of QSM to observe each change separately (B). Separation of positive and negative sources could be useful for this purpose, which could demonstrate details of MS lesions.
There are multiple typical MS lesions in left parietal white matter. Majority of them are dark signal on T1-weighted images, and dark signal rim on SWI. These lesions were paramagnetic on QSM with strong paramagnetic rims. On separation maps, peripheral positive source deposition and diffuse loss of negative sources. Both are well matched to iron rim and demyelination of MS lesion pathology. Note the central portion of lesions were paramagnetic over the surrounding white matter on magnified QSM (box), which is due to loss of negative sources (box on χneg).
While T2 FLAIR and QSM showed different natures of large periventricular MS lesions (a), this heterogeneity of MS lesions can be characterized better using separated maps. Both blue and yellow arrows were paramagnetic on QSM. However, separated maps showed contribution of both positive and negative source changes in blue arrow portion. χneg map suggested that in yellow arrow portion loss of negative source (demyelination) is responsible for paramagnetic appearance on QSM. Another patient’s subcortical paramagnetic lesion (arrowhead on b) showed similar changes.
A lesion (orange arrow) shows rim enhancement at first, with large defect on χneg , suggesting acute demyelination. This lesion had mild iron deposition on χpos. During follow-up, size on χneg were decreased which suggesting remyelination, while iron deposition was not (on χpos). Another lesion (yellow arrow) with paramagnetic rim showed progression of χneg defect, suggesting ‘chronic active’ nature of this lesion. A new lesion (arrowhead) was seen at third follow-up MR. It shows both iron deposition and demyelination, suggesting relatively new and active disease process.