Fiber orientation-dependent white matter contrast in gradient echo MRI

Wharton, Samuel; Bowtell, Richard W.

Abstract

Recent studies have shown that there is a direct link between the orientation of the nerve fibers in white matter (WM) and the contrast observed in magnitude and phase images acquired using gradient echo MRI. Understanding the origin of this link is of great interest because it could offer access to a new diagnostic tool for investigating tissue microstructure. Since it has been suggested that myelin is the dominant source of this contrast, creating an accurate model for characterizing the effect of the myelin sheath on the evolution of the NMR signal is an essential step toward fully understanding WM contrast. In this study, we show by comparison of the results of simulations and experiments carried out on human subjects at 7T, that the magnitude and phase of signals acquired from WM in vivo can be accurately characterized by (i) modeling the myelin sheath as a hollow cylinder composed of material having an anisotropic magnetic susceptibility that is described by a tensor with a radially oriented principal axis, and (ii) adopting a two-pool model in which the water in the sheath has a reduced T2 relaxation time and spin density relative to its surroundings, and also undergoes exchange. The accuracy and intrinsic simplicity of the hollow cylinder model provides a versatile framework for future exploitation of the effect of WM microstructure on gradient echo contrast in clinical MRI.

Gradient echo (GE) MRI is widely used in imaging the human brain, because both the phase and magnitude of the complex NMR signal measured with GE sequences can be used to create high-resolution images that show strong contrast between different types of brain tissue (1). Recent studies have shown that there is a direct link between the orientation of the nerve fibers in white matter (WM) with respect to the magnetic field and the contrast observed in magnitude and phase images (2⇓⇓⇓–6). Although the origin of this link is currently not fully understood, orientation-dependent contrast is of great interest because it could offer researchers access to a new diagnostic tool for investigating tissue microstructure using MRI.

It has recently been suggested that the myelin sheaths that surround axons are the dominant source of WM contrast in GE MRI (7, 8). Creating an accurate model for characterizing the effect of the myelin sheath on the evolution of the magnitude and phase of the NMR signal is consequently an essential step toward fully understanding WM contrast and its relationship to fiber orientation. Such a model must incorporate two main features: (i) a representation of the microscopic spatial variation of resonant frequency, due to the myelin compartment—isotropic and anisotropic magnetic susceptibility effects (2, 9, 10) and chemical exchange of protons between water and macromolecules (11, 12), have been proposed as mechanisms through which myelin could perturb the resonant frequency in WM; (ii) a signal-weighting scheme to account for the reduced T2 relaxation time constant of the myelin water relative to that of water found outside the myelin sheath (13⇓–15).

In this study, we show by comparison of the results of simulations and experiments that the fiber orientation dependence of the magnitude and phase of signals acquired from WM in vivo can be accurately characterized by (i) modeling the myelin sheath as a hollow cylinder composed of material having an anisotropic susceptibility that is described by a tensor with a radially oriented principal axis, and (ii) adopting a two-pool model in which the water in the sheath has a reduced T2 relaxation constant and effective spin density relative to its surroundings, and also undergoes exchange.

Citation

Wharton, S., & Bowtell, R. W. (2012). Fiber orientation-dependent white matter contrast in gradient echo MRI. Proceedings of the National Academy of Sciences, 109(45), https://doi.org/10.1073/pnas.1211075109

• Journal Article Type: Article
• Publication Date: Nov 6, 2012
• Deposit Date: Mar 28, 2014
• Publicly Available Date: Mar 28, 2014
• Journal: Proceedings of the National Academy of Sciences
• Print ISSN: 0027-8424
• Electronic ISSN: 1091-6490
• Publisher: National Academy of Sciences
• Peer Reviewed: Peer Reviewed
• Volume: 109
• Issue: 45
• DOI: https://doi.org/10.1073/pnas.1211075109
• Public URL: https://nottingham-repository.worktribe.com/output/712334
• Publisher URL: http://www.pnas.org/content/109/45/18559.full