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

Tobias D Faizy,Jan Sedlacik,Simon Hewera,Jens Fiehler,Christian Thaler,Susanne Gellißen,Ravinder Reddy,Hannes Leischner,Dominik Dotzauer,Gabriel Broocks,Daniel Kutzner,Fabian Flottmann,Dushyant Kumar,Jan-Patrick Stellmann

doi:10.1038/s41598-018-33112-8

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.

Highlights

Myelin is an important marker for healthy brain function and holds a crucial role in the composition of brain’s microstructure[1]
The obtained Myelin water fraction (MWF) values from both hemispheres were comparable and no significant differences of mean MWF measurements were found between the respective Regions of Interest (ROI) in the frontal, parietal and occipital white matter (WM) and CST of both sides (p > 0.05 for all ROIs)
Since no significant differences were detected between the hemispheres, mean MWF values of WM and CST-ROIs of both sides were used for Figs 2 and 3

Summary

Introduction

Myelin is an important marker for healthy brain function and holds a crucial role in the composition of brain’s microstructure[1]. A microstructural damage of myelin integrity is associated with many functional pathological processes and neurodegenerative diseases of the brain[2]. Myelin Water Imaging (MWI) is a powerful quantitative magnetic resonance imaging (MRI) technique for the assessment of the cerebral white matter (WM) microstructure[3]. Studies investigating age-dependent (demyelinating) changes of the MWF in normal aging brains are rare, albeit normal reference values are mandatory for the future application of MWI sequences in clinical settings and comparative patient studies. We sought to generate age-dependent normal values of the MWF in the WM of healthy subjects and investigated changes of the mean MWF related to age. We hypothesized that the MWF measurements obtained from the 3 mm and 5 mm sequences will be highly comparable and that MWF values measured in normal WM are age-dependent

Objectives

Methods

Results

Conclusion