In vivo assessment of myelination by phase imaging at high magnetic field

Abstract

The present study evaluated the potential of using the phase of T 2 * weighted MR images to characterize myelination during brain development and pathology in rodents at 9.4 T. Phase contrast correlated with myelin content assessed by histology and suggests that most contrast between white and cortical gray matter is modulated by myelin. Ex vivo experiments showed that gray-white matter phase contrast remains unchanged after iron extraction. In dysmyelinated shiverer mice, phase imaging correlated strongly with myelin staining, showing reduced contrast between white and gray matter when compared to healthy controls. We conclude that highresolution phase images, acquired at high field, allow assessment of myelination and dysmyelination.© 2011 Elsevier Inc. All rights reserved. IntroductionThe assessment of myelination in healthy subjects and following injury in humans and in animal models is one of the ways to determine the degree of cerebral integrity or the degree of injury in case of white matter disease like multiple sclerosis. In newborns, myelination of the posterior limb of the internal capsule, when assessed at term equivalent, has been shown to be a very robust predictor of motor impairment (Cowan and de Vries, 2005). A simple technique that would access the degree of myelination of white matter would be very useful in mature animal models of white matter injury such as multiple sclerosis and in immature animal models of white matter injury such as periventricular leukomalacia as well as in human studies. There are various methods available: one approach consists of quantification of myelin bond and free water fractions by a multiexponential analysis of the T 2 decay (Beaulieu et al., 1998;MacKay et al., 1994;Whittall and MacKay, 1989;Lancaster et al., 2003). This is generally performed using a CarrPurcell-Meiboom-Gill (CPMG) or a Turbo Spin-Echo sequences with multiple echo times (Beaulieu et al., 1998). Due to specific absorption rate (SAR) (especially at high fields) and timing constraints, the T 2 decay curve is often not fully sampled for an accurate quantification. Recently, it has been shown that myelin water fraction can also be measured using a multi-exponential analysis of the T 2 * decay in multislice multiple echo gradient echo sequence (Du et al., 2007;Hwang et al., 2010). The resulting myelin water fractions are highly dependent on the constraints introduced on the multi-exponential fitting procedure (Hwang et al., 2010) and suffer from significant inaccuracies in regions close to air-tissue interfaces. An alternative approach of a multicomponent relaxation analysis using multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) (Deoni et al., 2008) was applied successfully on infants from 3 to 11 months to quantify myelination (Deoni et al., 2011). Magnetization transfer represents an alternative approach to quantify myelin with new approaches refining its modelization by characterizing individually the relaxation and exchange rates of the free water and macromolec...

Studying cyto and myeloarchitecture of the human cortex at ultra-high field with quantitative imaging: R1, R2* and magnetic susceptibility

“…Myelin content does contribute to the gray and white matter contrast in phase imaging (C. Liu et al, 2011;Lodygensky et al, 2012) yet, not only is the myelin susceptibility anisotropic, its contribution to the measured phase images is driven by the microstructural compartmentalization of lipid organization and its orientation in respect to the static magnetic field (He and Yablonskiy, 2009;Luo et al, 2014;Wharton and Bowtell, 2013;Yablonskiy et al, 2012). These mechanisms are not taken into account in the COSMOS formalism, but they should only be dominating factors in regions where tissue is highly anisotropic (unlike grey matter).…”

Effects of white matter microstructure on phase and susceptibility maps

“…Recent studies have suggested that the source of the anisotropic susceptibility of WM is the myelin sheath (19,(30)(31)(32). This is composed of multiple lipid bilayers in which the lipid chains are radially oriented with respect to the approximately cylindrical sheath.…”

A modulated closed form solution for quantitative susceptibility mapping — A thorough evaluation and comparison to iterative methods based on edge prior knowledge

“…The other proposed contributor to the phase contrast, particularly between white and gray matter, is myelin where pathological demyelination has shown a decreased phase contrast between gray and white matter (C. Liu et al, 2011;Lodygensky et al, 2012) and good correlation was found between myelination and phase contrast during development. (Lodygensky et al, 2012).…”

“…Iron contributes to tissue contrast especially in the deep gray matter (globus pallidus, putamen and caudate) which has histologically derived high iron concentration showing good correlation with phase and susceptibility contrast (Bilgic et al, 2012;Schweser et al, 2011;Wharton and Bowtell, 2010). The other proposed contributor to the phase contrast, particularly between white and gray matter, is myelin where pathological demyelination has shown a decreased phase contrast between gray and white matter (C. Liu et al, 2011;Lodygensky et al, 2012) and good correlation was found between myelination and phase contrast during development. (Lodygensky et al, 2012).…”

“…The other proposed contributor to the phase contrast, particularly between white and gray matter, is myelin where pathological demyelination has shown a decreased phase contrast between gray and white matter (C. Liu et al, 2011;Lodygensky et al, 2012) and good correlation was found between myelination and phase contrast during development. (Lodygensky et al, 2012).In addition to the non-local effects associated with magnetic susceptibility, the chemical shift of water affected by macromolecules has been proposed to influence the measured phase (Luo et al, 2010;Shmueli et al, 2011;Zhong et al, 2008). More recently it was proposed (He and Yablonskiy, 2009) and demonstrated (Luo et al, 2013;Wharton and Bowtell, 2013;Yablonskiy et al, 2012) that the microstructural compartmentalization in the organization of lipids on the cellular and subcellular level (e.g.…”