Abstract
The traditional approach for measuring myelin-associated water with quantitative magnetic resonance imaging (MRI) uses multi-echo T2 relaxation data to calculate the myelin water fraction (MWF). A fundamentally different approach, abbreviated “mcDESPOT”, uses a more efficient steady-state acquisition to generate an equivalent metric (fM). Although previous studies have demonstrated inherent instability and bias in the complex mcDESPOT analysis procedure, fM has often been used as a surrogate for MWF. We produced and compared multivariate atlases of MWF and fM in healthy human brain and cervical spinal cord (available online) and compared their ability to detect multiple sclerosis pathology. A significant bias was found in all regions (p < 10–5), albeit reversed for spinal cord (fM-MWF = − 3.4%) compared to brain (+ 6.2%). MWF and fM followed an approximately linear relationship for regions with MWF < ~ 10%. For MWF > ~ 10%, the relationship broke down and fM no longer increased in tandem with MWF. For multiple sclerosis patients, MWF and fM Z score maps showed overlapping areas of low Z score and similar trends between patients and brain regions, although those of fM generally had greater spatial extent and magnitude of severity. These results will guide future choice of myelin-sensitive quantitative MRI and improve interpretation of studies using either myelin imaging approach.
Highlights
The traditional approach for measuring myelin-associated water with quantitative magnetic resonance imaging (MRI) uses multi-echo T2 relaxation data to calculate the myelin water fraction (MWF)
Five of the 28 participants had to be excluded from the MWF and fM spinal cord atlases, due to imaging artefacts that rendered their GRAdient-echo and Spin-Echo (GRASE) or mcDESPOT data unusable
Mean MWF and fM region of interest (ROI) values across all healthy control participants differed significantly (p < 10–5) for all ROIs. fM values were higher than MWF in all brain ROIs by a factor of ~ 2, except for the posterior internal capsule where values were more similar (fM = 19.5 ± 1.2%, MWF = 17.6 ± 4.0%) and the caudate where fM was larger by a factor of ~ 3 (fM = 10.0 ± 3.3%, MWF = 3.0 ± 1.8%)
Summary
The traditional approach for measuring myelin-associated water with quantitative magnetic resonance imaging (MRI) uses multi-echo T2 relaxation data to calculate the myelin water fraction (MWF). MWF and fM Z score maps showed overlapping areas of low Z score and similar trends between patients and brain regions, those of fM generally had greater spatial extent and magnitude of severity These results will guide future choice of myelin-sensitive quantitative MRI and improve interpretation of studies using either myelin imaging approach. The myelin water fraction (MWF) metric can be calculated as the signal contribution from T2 relaxation times associated with myelin water divided by the total signal This model neglects the presence of non-aqueous protons and the effects of magnetization exchange between water pools[2,3], the MWF has been shown to correlate well with quantitative histopathologic measures of myelin density[4,5,6]. Compared to myelin imaging with multi-echo T2 relaxation, mcDESPOT is appealing for its intrinsic acquisition e fficiency[10], which can be leveraged to improve coverage, resolution, or acquisition time, and for its additional quantitative metrics, such as T 1 and exchange rate constants, which can provide supplemental information
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