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 T
1w and T
2w
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 T
1 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
mm
3, 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 PD
w
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 sequence
7 was acquired as follows: resolution=1.5x1.5x4
mm
3, 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, T
1w,
T
2w, and FLAIR images were acquired.
Data processing and analysis:
All images were registered to the T
2w 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 mm
3).
Lesions in periventricular white matter (mean ROI volume=43±12 mm
3) were categorized
as T
1 isointense and T
1 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 T
1 isointense lesion
was compared with that of T
1 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 T
1 lesions, both SE- and ViSTa-MWIs showed
significant difference between T
1 isointense and T
1 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 T
1
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.
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