Quantitative magnetic resonance mapping of the myelin bilayer reflects pathology in multiple sclerosis brain tissue

Abstract

Multiple sclerosis (MS) is a neuroinflammatory disease characterized by loss of myelin (demyelination) and, to a certain extent, subsequent myelin repair (remyelination). To better understand the pathomechanisms underlying de- and remyelination and to monitor the efficacy of treatments aimed at regenerating myelin, techniques offering noninvasive visualizations of myelin are warranted. Magnetic resonance (MR) imaging has long been at the forefront of efforts to visualize myelin, but it has only recently become feasible to access the rapidly decaying resonance signals stemming from the myelin lipid-protein bilayer itself. Here, we show that direct MR mapping of the bilayer yields highly specific myelin maps in brain tissue from patients with MS. Furthermore, examination of the bilayer signal behavior is found to reveal pathological alterations in normal-appearing white and gray matter. These results indicate promise for in vivo implementations of the myelin bilayer mapping technique, with prospective applications in basic research, diagnostics, disease monitoring, and drug development.

Myelin bilayer mapping in the human brain in vivo

“…In this exploratory work, an in vivo technique for myelin bilayer mapping in the human head was developed from principles established in ex vivo tissue samples. 6,9,10 Using the proposed technique, quantitative myelin bilayer maps of human brain were obtained in vivo with adequate SNR, resolution, and depiction fidelity.…”

“…High myelin specificity of myelin bilayer maps produced by the three-component fitting procedure was validated by myelin histopathology in ex vivo studies. 9,10 The same methodological principles were implemented for the in vivo technique, and, consequently, the myelin bilayer map presented here is expected to be similarly specific for myelin. This is supported by the equivalence of HYFI and SPI data found in simulations, the overall quality of the fitted maps, and the correspondence between the myelin bilayer map and known myelin distribution of WM and GM structures seen in the anatomical reference image.…”

“…The maps demonstrated sensitivity to myelin pathology and high specificity for myelin. 10 These properties would be valuable to study the live brain, calling for an in vivo technique with the same functionality.…”

3D balanced SSFP UTE MRI for multiple contrasts whole brain imaging

“…Previous UTE studies have measured uT 2 values of 0.4, 40 0.5-0.7, 23,30 and 0.2 ms. 9 The differences could be caused by the limited TE samples, and/or contamination by myelin water, which has T 2 value of around 15 ms. Other studies have used spectroscopy or ZTE and fit super-Lorentzian line-shapes 41 to uT 2 components for myelin lipid bilayer and other non-aqueous protons. These have reported T 2min values of 0.01-0.1 ms in WM tissue samples 20,42,43 and also used these values to fit in vivo relaxometry data. 44 These studies concluded that a component with T 2min of 5.5 𝜇s and chemical shift of 1.1 ppm corresponds to the myelin bilayer, while a component with T 2min of 100 𝜇s and chemical shift of 2.1 ppm corresponds to other non-aqueous protons such as cell membranes and proteins.…”