Myelin volume fraction imaging with MRI

Abstract

MRI is a valuable tool to assess myelin during development and demyelinating disease processes. While multiexponential T2 and quantitative magnetization transfer measures correlate with myelin content, neither provides the total myelin volume fraction. In many cases correlative measures are adequate; but to assess microstructure of myelin, (e.g. calculate the g-ratio using MRI), an accurate measure of myelin volume fraction is imperative. Using a volumetric model of white matter, we relate MRI measures of myelin to absolute measures of myelin volume fraction and compare them to quantitative histology. We assess our approach in control mice along with two models of hypomyelination and one model of hypermyelination and find strong agreement between MRI and histology amongst models. This work investigates the sensitivities of MRI myelin measures to changes in axon geometry and displays promise for estimating g-ratio from MRI.

Analysis of White Matter Damage in Patients with Multiple Sclerosis via a Novel In Vivo MR Method for Measuring Myelin, Axons, and G-Ratio

“…Magnetization transfer imaging is one of these, and quantitative magnetization transfer imaging has shown a strong correlation with quantitative histology. 34 MR studies evaluating g-ratio have mostly been based on magnetization transfer imaging. 12,15,18 However, quantitative magnetization transfer imaging requires approximately 30 minutes for acquisition, and it is still unrealistic for routine use in a clinical setting.…”

Three‐Dimensional Lesion Phenotyping and Physiologic Characterization Inform Remyelination Ability in Multiple Sclerosis

“…Larger chronic lesions with smoother textures are characterized by a paucity of repair‐related metabolic activity and would be expected to remain static over time. Although our results suggest that studying lesion metabolism along with their 3D shape and texture informs the capacity for remyelination, validating this capacity with longitudinal study and myelin imaging techniques to specifically assess myelin integrity in larger groups will be required . Furthermore, validating the metrics used to assess lesion phenotypes with histopathological data would be essential to define a threshold for 3D texture and shape data to be applied in clinical practice.…”

Formalin tissue fixation biases myelin‐sensitive MRI

“…Several different methods for regularization of multi‐exponential relaxation analysis have been reported in the literature and are available in the MERA software package: minimum‐curvature and minimum‐energy constraints, which impose no assumptions on number of signal pools; and a multiple‐Gaussian constraint, which does impose such an assumption. We applied 2 of these methods, minimum‐curvature and multiple (2)‐Gaussian, to our data.…”

“…MWI data were acquired using a custom 3D multi‐echo spin echo sequence (remmiRARE, Vanderbilt University Institute of Imaging Science, Nashville, TN) (Figure B) with the following parameters: TR = 520 ms, 32 echoes, echo spacing = 5 ms, nonselective RF excitation and refocusing pulses, excitation/refocusing pulse duration = 200/125 µs, pulse bandwidths = 6.4 kHz, constant amplitude crusher gradients, 4 signal averages, FOV = 20 × 20 × 40 mm 3 , resolution = 250 × 250 × 500 μm 3 , and scan time = 7 h 23 min.…”

“…To produce T 2 spectra, echo‐train signals were fitted voxel‐wise by nonnegative least squares to an array of 100 extended phase graph‐defined exponentials under both minimum‐curvature (regularization weight = 0.002) and 2‐Gaussian‐pool (width = 5) constraints using the MERA (Multi‐Exponential Relaxation Analysis) toolbox . Additional fitting settings and parameters were time constants spaced logarithmically from 2.5 to 500 ms, and B 1 fitting for nonideal refocusing pulses in the range of 150° to 210° …”