Assessing the differential sensitivities of wave-CAIPI ViSTa myelin water fraction and magnetization transfer saturation for efficiently quantifying tissue damage in MS
Introduction
Reliable, in vivo quantification of myelin in human brain white matter (WM) is vital for the study of demyelinating diseases, human brain development, and healthy aging (Laule and Moore, 2018). In this context, Magnetization Transfer saturation (MTsat) (Mohammadi et al., 2015) is a recognized technique that employs the exchange of semi-solid, macromolecular protons with free water to sensitize the MRI signal to detect myelin. Myelin Water Fraction (MWF) imaging, by comparison, seeks to extract a relative measure of myelin based on the fraction of water molecules localized between the myelin bilayers. This is traditionally carried out using multi-component decay analysis of either the transverse relaxation time (T2) (MacKay et al., 1994) or apparent transverse relaxation time (T2*) spectrum (Hwang et al., 2010). When applied in concert, MTsat and MWF imaging offer important, complementary information about white matter damage due to neuroinflammation, axonal loss and demyelination in MS (Kolind et al., 2008, Laule et al., 2003).
The direct Visualization of Short Transverse relaxation time component (ViSTa) method was recently introduced to selectively image the short T1, myelin water signal component in human brain white matter (Choi et al., 2019; Oh et al., 2013). Compared to other MWF mapping techniques, ViSTa has the advantage of not requiring the fitting of an ill-posed signal model and additionally providing high quality images (Jung et al., 2018; Oh et al., 2013). However, a challenge related to its application is the longer overall MRI acquisition time associated with ViSTa scans, relative to more standard the T2 relaxation based approaches (Labadie et al., 2014; MacKay et al., 1994). In this study, we addressed this challenge using an accelerated wave encoding scheme for human brain myelin water imaging at 3 T. Wave encoding is a recently introduced, data sampling technique that enables imaging at high acceleration factors, while significantly mitigating signal-to-noise ratio penalty (Bilgic et al., 2015; Gagoski et al., 2015; Wu et al., 2018).
Herein, we systematically evaluated the relationship between MWF, quantified using T1-based Wave-CAIPI ViSTa (Wu et al., 2018) and MTsat (Helms et al., 2008) in MS and healthy brain tissue. No previous comparative evaluation exists of the relationship between MTsat and quantitative T1-based myelin water fraction methods. Further, there is very limited precision analysis in the literature regarding the application of ViSTa MWF for monitoring NAWM changes in MS. As an additional feature, we evaluated the relationship between the myelin sensitive MRI parameters and MS clinical measures to probe their potential clinical utility.
Section snippets
Study design
Our MRI study was approved by the local institutional review board of the McGill University Health centre. Thirty-nine participants were recruited for our study. Twenty-nine clinically confirmed MS patients were recruited from the Multiple Sclerosis Clinic of the Montreal Neurological Institute (MNI) and Hospital and underwent MRI scanning. Patients were enrolled in our study if they were greater than 18 years of age and had been diagnosed with MS by a neurologist at the MNI. All subjects in
Results
Fig. 3 presents an example of co-registered ViSTa MWF and MTsat images in the 1 mm3 isotropic MNI space. Automatic tissue classifications of NAWM, high confidence CGM, DGM and MS white matter lesions are overlaid in red for the images in the bottom row. Fig. 4 demonstrates examples of automatically segmented lesions overlaid on ViSTa MWF, MTsat and FLAIR images. Representative, magnified views of white matter lesions, along with the corresponding lesion segmentations derived from the Bayesian
Discussion
Our study documents the combined application of Wave-CAIPI ViSTa MWF and MTsat for robust, efficient quantitative imaging of tissue damage in NAWM, white matter lesions, CGM, and DGM tissue of MS patients. MWF derived from the ViSTa sequence demonstrated higher sensitivity compared to MTsat, for quantifying signals of demyelination in MS normal-appearing white matter. This was true for all the statistical measures we tested, including median, IQR and skewness. Notably however, MTsat proved more
Conclusions
We implemented a fast, practical method to measure MWF in healthy control and MS patient brain by sensitizing the MRI signal to the short T1 relaxation, myelin water component. We also characterized, for the first time, group-level distributions of ViSTa MWF and MTsat in NAWM, CGM, DGM and WM lesions. The distributions were rigorously compared using generalized statistical measures. ViSTa MWF demonstrated higher sensitivity to signals related to demyelination in MS normal-appearing white
CRediT authorship contribution statement
Ahmed M. Elkady: Conceptualization, Methodology, Software, Validation, Formal analysis, Investigation, Writing – original draft, Writing – review & editing. Zhe Wu: Conceptualization, Methodology, Software, Validation, Investigation, Data curation, Writing – review & editing. Ilana R. Leppert: Methodology, Software, Validation, Investigation, Data curation. Douglas L. Arnold: Investigation, Resources, Writing – review & editing, Funding acquisition. Sridar Narayanan: Conceptualization,
Declarations of Competing Interest
None.
Acknowledgments
We are especially grateful to all the participants in our study. The authors also wish to thank Ms. Rozie Arnaoutelis for her invaluable assistance obtaining ethics approvals and consents, as well as scheduling examinations for both patients and controls.
Funding
The authors gratefully acknowledge funding support for this study from the Canadian Institutes of Health Research (grant No. 201610PJT-377721). Ahmed Elkady gratefully acknowledges scholarship support from MITACS Accelerate (award number FR33832).
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