Quantitative susceptibility mapping versus phase imaging to identify multiple sclerosis iron rim lesions with demyelination

Abstract

Background and purpose: To compare quantitative susceptibility mapping (QSM) and high-pass-filtered (HPF) phase imaging for (1) identifying chronic active rim lesions with more myelin damage and (2) distinguishing patients with increased clinical disability in multiple sclerosis.

Methods: Eighty patients were scanned with QSM for paramagnetic rim detection and Fast Acquisition with Spiral Trajectory and T2prep for myelin water fraction (MWF). Chronic lesions were classified based on the presence/absence of rim on HPF and QSM images. A lesion-level linear mixed-effects model with MWF as the outcome was used to compare myelin damage among the lesion groups. A multiple patient-level linear regression model was fit to establish the association between Expanded Disease Status Scale (EDSS) and the log of the number of rim lesions.

Results: Of 2062 lesions, 188 (9.1%) were HPF rim+/QSM rim+, 203 (9.8%) were HPF rim+/QSM rim-, and the remainder had no rim. In the linear mixed-effects model, HPF rim+/QSM rim+ lesions had significantly lower MWF than both HPF rim+/QSM rim- (p < .001) and HPF rim-/QSM rim- (p < .001) lesions, while the MWF difference between HPF rim+/QSM rim- and HPF rim-/QSM rim- lesions was not statistically significant (p = .130). Holding all other factors constant, the log number of QSM rim+ lesion was associated with EDSS increase (p = .044). The association between the log number of HPF rim+ lesions and EDSS was not statistically significant (p = .206).

Conclusions: QSM identifies paramagnetic rim lesions that on average have more myelin damage and stronger association with clinical disability than those detected by phase imaging.

Keywords: chronic active lesions; high-pass-filtered phase imaging; multiple sclerosis; myelin water fraction (MWF); paramagnetic rim; quantitative susceptibility mapping (QSM).

Figure 1.

Example of phase images obtained by high-pass filtering using a 2D circularly symmetric Hanning kernel size of 32 (A), 64 (B), 96 (C), 128 (D), 160 (E), and 192 (F) pixels. The kernel size of 128 pixels was used in this study, which was deemed to provide the best visual depiction of rim lesions on the phase image (red arrows).

Figure 2.

Example of three chronic fluid attenuated inversion recovery (FLAIR)-hyperintense white matter lesions with and without paramagnetic rim appearance (red arrows) from three relapse-remitting MS patients. Top row: a lesion appears with a dark rim on the HPF phase image and a hyperintense rim on the QSM image, which is consistent with a chronic active lesion with iron-laden microglia and macrophages in the lesion rim. Middle row: a lesion has a rim on the HPF phase image but appears nodular without rim on QSM, which may be due to demyelination in the lesion center. Bottom row: a lesion is not visible and has no rim on both HFP and QSM images, suggesting an old chronic lesion with loss of both myelin and iron. In this study, all lesions with rim on QSM also had rim on HPF, and there were no lesions in the HPF rim−/QSM rim+ category. In this and the subsequent Figures 3 and 4, the QSM and HPF images are shown using a display window of [−125 125] ppb and [−200 200] a.u., respectively.

Figure 3.

Examples of fluid attenuated inversion recovery (FLAIR)-hyperintense and HPF rim+/QSM rim+ lesions with full or partial rim appearance on both HPF and QSM images (red arrows) and their myelin loss as measured by myelin water fraction (MWF). Note the improved lesion conspicuity and reduced noise on the QSM image compared to the HPF phase image. The HPF rim+/QSM rim+ lesions tended to have severe demyelination as demonstrated by the much lower MWF value in the lesion center compared to the surrounding normal appearing white matter. In this and the subsequent Figure 4, the MWF maps are shown using a display window of [0 0.2].

Figure 4.

Examples of fluid attenuated inversion recovery (FLAIR)-hyperintense and HPF rim+/QSM rim− lesions with a dark paramagnetic rim on the HPF phase image but no rim appearance on QSM (red arrows) and their myelin water fraction (MWF) values. These lesions showed myelin loss, but the degree of demyelination tended to be less severe compared to that of HPF rim+/QSM rim+ lesions shown in Fig. 3.

Figure 5.

Box plots showing summary statistics of the mean lesion myelin water fraction (MWF) value, expressed in percent, for the three lesion groups classified based on the paramagnetic rim appearance on both HPF phase and QSM images. Liner mixed-effects model analysis showed that lesions with rim on both HPF and QSM (HPF rim+/QSM rim+) on average had significantly lower MWF compared to the other two groups, holding all other factors constant. Lesions with rim on HPF phase image only (HPF rim+/QSM rim−) tended to have lower MWF compared to those without any rim (HPF rim−/QSM rim−), but the difference did not reach statistical significance. Significance on the plot are from the p-values from the linear mixed effects model: *** < 0.001.

Figure 6.

Box plots comparing log-transformed lesion volume on fluid attenuated inversion recovery image for three lesion groups classified based on rim appearance on both HPF phase and QSM images. Linear mixed-effects model analysis shows that lesions with rim on either HPF or QSM were on average significantly larger than those without rim. Lesions in the HPF rim+/QSM rim+ group were also significantly larger than those in the HPF rim+/QSM rim− group. Significance on the plot are from the p-values from the linear mixed effects model: *** < 0.001.