A Quantitative Evaluation of Normal Appearing White Matter in Multiple Sclerosis: ViSTa MWI and SE MWI.
Joon Yul Choi1, In Hye Jeong2, Se-Hong Oh3, Chang-Hyun Oh4,5, Ho Jin Kim2, and Jongho Lee1

1Laboratory for Imaging Science and Technology, Department of Electrical and Computer Engineering, Seoul National University, Seoul, Korea, Republic of, 2Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, Korea, Republic of, 3Imaging Institute, Cleveland Clinic Foundation, Cleveland, OH, United States, 4Department of Electronics and Information Engineering, Korea University, Seoul, Korea, Republic of, 5ICT Convergence Technology Team for Health&Safety, Korea University, Seoul, Korea, Republic of

Synopsis

This study investigated the applicability of ViSTa-MWI for the detection of myelin damage in MS. The results show ViSTa-MWI sensitively detects normal appearing white matter damage with better reliability than SE-MWI. Additionally, ViSTa-MWI can discriminate T1 isointense lesions from T1 hypointense lesions.

Purpose

Multiple sclerosis (MS) is often characterized by focal lesions in white matter, which are visible in T1w and T2w images. However, MRI lesion load has shown a poor to moderate correlation with clinical disability. On the other hand, normal appearing white matter (NAWM) damage has been suggested to have a better correlation with the clinical disability.1 A few studies using myelin water imaging (MWI), which is as a biomarker for myelin, have revealed reduction in MW fraction (MWF) in NAWM in MS patients.2,3 However, conventional spin-echo MWI (SE-MWI) has limited image quality due to an ill-conditioned data fitting process. Recently, we have proposed a new MWI method (ViSTa-MWI) that provides improved image quality and reproducibility compared to SE-MWI. The signal characteristics such as magnitude decay, phase evolution, and MT effects have confirmed the origin of the ViSTa signal as myelin water.4-6 In this study, we investigated the applicability of ViSTa-MWI for the detection of myelin damage in MS. We compared NAWM MWF in MS patients with that in healthy controls (HC) using ViSTa-MWI and SE-MWI. Additionally, we explored the difference in MWF between T1 isointense and hypointense lesions using the two MWIs.

Methods

Twenty seven MS and 18 HC were participated in this study using 3T (IRB-approved). ViSTa-MWI: a 3D segmented EPI based ViSTa sequence was acquired using following parameters: resolution=1.5x1.5x4 mm3, 32 slices, TR/TE=1160/6.6 ms, TI1/TI2/TD=560/220/380 ms, partial k-space=6/8, EPI factor=15, and scan time=6 min 53 sec. This scan was acquired twice to match the scan time with SE-MWI. To quantify MWF, a PDw GRE sequence based on the same EPI as ViSTa was acquired (TR=75 ms, flip angles=5° for lesion and 28° for NAWM, and each scan time=30 sec). The ViSTa-MWF was calculated by dividing the ViSTa data by the GRE data and multiplying a scaling factor. The resulting ViSTa-MWF is referred to as apparent MWF (aMWF) due to the scaling factor and is approximately the half of SE-MWF (Table 1).4 SE-MWI: For 3D SE-MWI, a modified GRASE sequence7 was acquired as follows: resolution=1.5x1.5x4 mm3, 28 slices, TR=1000 ms, TE=10:10:320 ms, EPI factor=3, partial k-space=6/8, and scan time=14 min 5 sec. The data were processed using a stimulated echo corrected regularized NNLS method.7-9 To detect lesions, T1w, T2w, and FLAIR images were acquired. Data processing and analysis: All images were registered to the T2w images.10 Global NAWM masks were generated in the FLAIR images after excluding lesions. For regional NAWM analysis, ROIs were drawn manually avoiding lesions (mean ROI volume=190±107 mm3). Lesions in periventricular white matter (mean ROI volume=43±12 mm3) were categorized as T1 isointense and T1 hypointense lesions. To evaluate a reliability of ViSTa- and SE-MWIs, intra-subject coefficient of variation (COV = [standard deviation of MWF]/[mean MWF]; Fig.1) in each ROI and inter-subject COV (Fig. 2) were calculated in HC. To compare NAWM MWF in MS with that in HC, a statistical analysis was performed in each ROI in both MWIs. Additionally, the sensitivity of the two MWIs to NAWM damage in early MS patients (less than 2 years) was investigated by comparing MWF in the early MS patients with that of HC in the global NAWM. Lastly, MWF of T1 isointense lesion was compared with that of T1 hypointense lesion in both MWIs. Student’s t-test was used for the statistical analysis.

Results

Figures 1 and 2 demonstrate that ViSTa-MWI has smaller intra-subject and inter-subject COVs compared to SE-MWI in HC, confirming that ViSTa-MWI has a higher reliability than SE-MWI. When exploring reduction in NAWM MWF in MS using the two MWIs, the p-values of ViSTa-MWI are smaller than those of SE-MWI (Table 1). For the early MS patients, only ViSTa-MWI successfully discriminated them from HC, demonstrating a higher sensitivity of ViSTa-MWI in the NAWM change (Fig. 3). When investigating MWF in T1 lesions, both SE- and ViSTa-MWIs showed significant difference between T1 isointense and T1 hypointense lesions (Fig. 4).

Discussion and Conclusion

In this study, we demonstrate that ViSTa-MWI can be used to detect myelin damage in NAWM and T1 lesions with better image quality and reliability than SE-MWI. The smaller p-values in ViSTa-MWI than those in SE-MWI (Table 1 and Figs. 3 and 4) also suggest that ViSTa-MWI has a stronger statistical power than SE-MWI.

Acknowledgements

This research was supported by the Brain Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2015M3C7A1031969).

This work was funded by UCB Pharma, Korea.

References

1. Barkhof F, The clinic-radiological paradox in multiple sclerosis revisited. Curr Opin Neurol. 2002;15(3):239-245.

2. Laule C, Vavasour IM, Moore GR, et al. Water content and myelin water fraction in multiple sclerosis. A T2 relaxation study. J Neurol. 2004;251(3):284-293.

3. Kolind S, Matthews L, Johansen-Berg H, et al. Myelin water imaging reflects clinical variability in multiple sclerosis. Neuroimage. 2012;60(1):263-270.

4. Oh SH, Bilello M, Schindler M, et al. Direct visualization of short transverse relaxation time component (ViSTa). Neuroimage. 2013;83:485-492.

5. Kim D, Lee HM, Oh SH, et al. Probing signal phase in direct visualization of short transverse relaxation time component (ViSTa). Magn Reson Med. 2015;74(2):499-505.

6. Lee HM, Kim D, Oh SS, et al. The phase and Magnetization transfer characteristics of a novel myelin water imaging method (ViSTa). ISMRM, 2014, #338.

7. Prasloski T, Rauscher A, MacKay AL, et al. Rapid whole cerebrum myelin water imaging using a 3D GRASE sequence. Neuroimage. 2012;63(1):533-539.

8. MacKay A, Whittall K, Adler J, et al. In vivo visualization of myelin water in brain by magnetic resonance. Magn Reson Med. 1994;31(6):673-677.

9. Prasloski T, Mädler B, Xiang QS, et al. Applications of stimulated echo correction to multicomponent T2 analysis. Magn Reson Med. 2012;67(6):1803-1814.

10. Smith SM, Jenkinson M, Woolrich MW, et al. Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage. 2004;23 Suppl 1:S208-219.

Figures

Figure 1. Intra-subject COV for each ROI in healthy controls. Intra-subject COV was calculated by dividing standard deviation of MWF by mean MWF in each ROI in each subject. Then, the COVs were averaged across the subjects to compare reliability of MWF in SE-MWI and ViSTa-MWI.

Figure 2. Inter-subject COV for each ROI in healthy controls. Inter-subject COV was calculated by estimating standard deviation and mean of MWF across the subjects in each ROI. The results show ViSTa-MWI has smaller COV (i.e. higher reliability) than SE-MWI.

Table 1. Global and regional NAWM MWF for SE-MWI and aMWF for ViSTa-MWI (*p < 0.05).

Figure 3. Global NAWM MWF for SE-MWI and aMWF for ViSTa-MWI in early MS, total MS patients, and healthy controls (*p < 0.05). Only ViSTa-MWI successfully discriminated early MS patients from HC.

Figure 4. Statistical difference between T1 isointense and T1 hypointense lesions for SE-MWI and ViSTa-MWI (*p < 0.05) (A) and T1 isointense and T1 hypointense lesions on FLAIR, T1 weighted image, SE-MWI, and ViSTa-MWI (B).



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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