In vivo histology of the myelin g-ratio with magnetic resonance imaging

Stikov, Nikola; Campbell, Jennifer S. W.; Stroh, Thomas; Lavelée, Mariette; Frey, Stephen; Novek, Jennifer; Nuara, Stephen G.; Ho, Ming-Kai; Bedell, Barry J.; Dougherty, Robert F.; Leppert, Ilana R.; Boudreau, Mathieu; Narayanan, Sridar; Duval, Tanguy; Cohen‐Adad, Julien; Picard, Paul-Alexandre; Gąsecka, Alicja; Côté, Daniel; Pike, G. Bruce

doi:10.1016/j.neuroimage.2015.05.023

Cited by 268 publications

(436 citation statements)

References 56 publications

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“…The axonal volume fraction can now be estimated from neurite orientation dispersion and density imaging and the myelin volume fraction. 32,33 Therefore, the axonal volume fraction will be combined with the myelin partial volume to further clarify the MS disease process in a future study.…”

Section: Discussionmentioning

confidence: 99%

Utility of a Multiparametric Quantitative MRI Model That Assesses Myelin and Edema for Evaluating Plaques, Periplaque White Matter, and Normal-Appearing White Matter in Patients with Multiple Sclerosis: A Feasibility Study

Hagiwara

Hori²,

Yokoyama

et al. 2016

AJNR Am J Neuroradiol

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BACKGROUND AND PURPOSE: T1 and T2 values and proton density can now be quantified on the basis of a single MR acquisition. The myelin and edema in a voxel can also be estimated from these values. The purpose of this study was to evaluate a multiparametric quantitative MR imaging model that assesses myelin and edema for characterizing plaques, periplaque white matter, and normal-appearing white matter in patients with MS.

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Section: Discussionmentioning

confidence: 99%

Utility of a Multiparametric Quantitative MRI Model That Assesses Myelin and Edema for Evaluating Plaques, Periplaque White Matter, and Normal-Appearing White Matter in Patients with Multiple Sclerosis: A Feasibility Study

Hagiwara

Hori²,

Yokoyama

et al. 2016

AJNR Am J Neuroradiol

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“…In vivo mapping of myelin density15 and g‐ratio16; iron deposition17; sodium concentration18; inflammation and axonal injury19 are examples of quantitative MRI techniques being developed to detect early multiple sclerosis pathology. Similar quantitative MRI metrics require extensive validation, in order to confirm their specificity and relevance to clinical outcomes 20, 21, 22…”

Section: Introductionmentioning

confidence: 99%

Neurite dispersion: a new marker of multiple sclerosis spinal cord pathology?

Grussu

Schneider

Tur

et al. 2017

Ann Clin Transl Neurol

259

243

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ObjectiveConventional magnetic resonance imaging (MRI) of the multiple sclerosis spinal cord is limited by low specificity regarding the underlying pathological processes, and new MRI metrics assessing microscopic damage are required. We aim to show for the first time that neurite orientation dispersion (i.e., variability in axon/dendrite orientations) is a new biomarker that uncovers previously undetected layers of complexity of multiple sclerosis spinal cord pathology. Also, we validate against histology a clinically viable MRI technique for dispersion measurement (neurite orientation dispersion and density imaging, NODDI), to demonstrate the strong potential of the new marker.MethodsWe related quantitative metrics from histology and MRI in four post mortem spinal cord specimens (two controls; two progressive multiple sclerosis cases). The samples were scanned at high field, obtaining maps of neurite density and orientation dispersion from NODDI and routine diffusion tensor imaging (DTI) indices. Histological procedures provided markers of astrocyte, microglia, myelin and neurofilament density, as well as neurite dispersion.ResultsWe report from both NODDI and histology a trend toward lower neurite dispersion in demyelinated lesions, indicative of reduced neurite architecture complexity. Also, we provide unequivocal evidence that NODDI‐derived dispersion matches its histological counterpart (P < 0.001), while DTI metrics are less specific and influenced by several biophysical substrates.InterpretationNeurite orientation dispersion detects a previously undescribed and potentially relevant layer of microstructural complexity of multiple sclerosis spinal cord pathology. Clinically feasible techniques such as NODDI may play a key role in clinical trial and practice settings, as they provide histologically meaningful dispersion indices.

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“…As opposed to DTI, which is sensitive to the partial volume averaging of fiber orientations, NODDI incorporates the curving and fanning of fibers into the model and is considered to be more robust for estimating the volume of axons. 12 Even though it was not explicitly designed for handling the crossing of fibers, a preliminary study has also shown the robustness of the NODDI model for crossing fibers.…”

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confidence: 99%