Age-Related Measurements of the Myelin Water Fraction derived from 3D multi-echo GRASE reflect Myelin Content of the Cerebral White Matter

Abstract

Myelin Water Fraction (MWF) measurements derived from quantitative Myelin Water Imaging (MWI) may detect demyelinating changes of the cerebral white matter (WM) microstructure. Here, we investigated age-related alterations of the MWF in normal aging brains of healthy volunteers utilizing two fast and clinically feasible 3D gradient and spin echo (GRASE) MWI sequences with 3 mm and 5 mm isotropic voxel size. In 45 healthy subjects (age range: 18–79 years), distinct regions of interest (ROI) were defined in the cerebral WM including corticospinal tracts. For the 3 mm sequence, significant correlations of the mean MWF with age were found for most ROIs (r < −0.8 for WM ROIs; r = −0.55 for splenium of corpus callosum; r = −0.75 for genu of corpus callosum; p < 0.001 for all ROIs). Similar correlations with age were found for the ROIs of the 5 mm sequence. No significant correlations were found for the corticospinal tract and the occipital WM (p > 0.05). Mean MWF values obtained from the 3 mm and 5 mm sequences were strongly comparable. The applied 3D GRASE MWI sequences were found to be sensitive for age-dependent myelin changes of the cerebral WM microstructure. The reported MWF values might be of substantial use as reference for further investigations in patient studies.

Myelin Water Atlas: A Template for Myelin Distribution in the Brain

“…We observed similar patterns of MWF variability across different ROIs in almost all participants (Fig ). The highly significant paired t ‐tests (Table ) and the consistent patterns of myelin variation between structures (Fig ) illustrate that MWF can assess subtle differences of myelin microstructure at an individual level, expanding upon previous work that reported group averages from smaller cohorts . Although other quantitative metrics (ie, MT ratio derived from MT experiments and fractional anisotropy by diffusion techniques) also detect differences within different WM ROIs, those observed differences may be influenced by nonmyelin‐related factors, such as extracellular water, fiber orientation, and axonal diameter.…”

“…Development of a normative myelin imaging atlas, to which individual patients can be compared, can address these challenges. Atlas‐based approaches for magnetic resonance (MR) methods influenced by myelin have been implemented for a number of different quantitative imaging techniques, including diffusion, T 1 , T 2 , MT, and mcDESPOT‐derived myelin water assessment …”

The Myelin Water Fraction Serves as a Marker for Age-Related Myelin Alterations in the Cerebral White Matter – A Multiparametric MRI Aging Study

“…Accordingly, biomarkers sensitive for these specific developmental patterns of age-related myelin changes are of great interest for researchers studying aging. While many related imaging studies predominantly reported of linear declines of diffusion-based metrics (Bennett et al, 2010;Lebel et al, 2012;Billiet et al, 2015;Rathee et al, 2016), only very few studies found a correlation of MWF estimates with age (Billiet et al, 2015;Arshad et al, 2016;Faizy et al, 2018;Bouhrara et al, 2019). Histopathologically, normal brain-aging is marked by WM degeneration, including myelin pallor (Kemper, 1994), loss of myelinated nerve fibers (Bartzokis, 2004;Bartzokis et al, 2004) and malformation of myelin sheaths (Peters, 2002;Gunning-Dixon et al, 2009).…”

Multi‐spin echo T2 relaxation imaging with compressed sensing (METRICS) for rapid myelin water imaging

“…[9][10][11][12][13] Increasingly, MWF has also been applied in more fundamental fields such as neurobiology and genetics. [14][15][16] In addition to the MWF, the geometric mean T 2 of the IEW peak (IET2) can be reported; both measures have shown clinical relevance. 17 Reproducibility of MWF values has been demonstrated in multi-site and multi-vendor studies, 18,19 but widespread clinical application of MWI has been slowed by long acquisition times.…”