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

<p>Objective: Conventional 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 orienta...

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Huvudupphovsmän: Grussu, F, Schneider, T, Tur, C, Yates, R, Tachrount, M, Ianuş, A, Yiannakas, M, Newcombe, J, Zhang, H, Alexander, D, Deluca, G, Gandini Wheeler-Kingshott, C
Materialtyp: Journal article
Publicerad: Wiley 2017
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author Grussu, F
Schneider, T
Tur, C
Yates, R
Tachrount, M
Ianuş, A
Yiannakas, M
Newcombe, J
Zhang, H
Alexander, D
Deluca, G
Gandini Wheeler-Kingshott, C
author_facet Grussu, F
Schneider, T
Tur, C
Yates, R
Tachrount, M
Ianuş, A
Yiannakas, M
Newcombe, J
Zhang, H
Alexander, D
Deluca, G
Gandini Wheeler-Kingshott, C
author_sort Grussu, F
collection OXFORD
description <p>Objective: Conventional 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.</p><p> Methods: We 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.</p><p> Results: We 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 &lt; 0.001), while DTI metrics are less specific and influenced by several biophysical substrates.</p><p> Interpretation: Neurite 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.</p>
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spelling oxford-uuid:35ae631f-b7a3-4ba3-8da7-b5edfa2bbcc72022-03-26T13:33:24ZNeurite dispersion: A new marker of multiple sclerosis spinal cord pathology?Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:35ae631f-b7a3-4ba3-8da7-b5edfa2bbcc7Symplectic Elements at OxfordWiley2017Grussu, FSchneider, TTur, CYates, RTachrount, MIanuş, AYiannakas, MNewcombe, JZhang, HAlexander, DDeluca, GGandini Wheeler-Kingshott, C<p>Objective: Conventional 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.</p><p> Methods: We 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.</p><p> Results: We 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 &lt; 0.001), while DTI metrics are less specific and influenced by several biophysical substrates.</p><p> Interpretation: Neurite 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.</p>
spellingShingle Grussu, F
Schneider, T
Tur, C
Yates, R
Tachrount, M
Ianuş, A
Yiannakas, M
Newcombe, J
Zhang, H
Alexander, D
Deluca, G
Gandini Wheeler-Kingshott, C
Neurite dispersion: A new marker of multiple sclerosis spinal cord pathology?
title Neurite dispersion: A new marker of multiple sclerosis spinal cord pathology?
title_full Neurite dispersion: A new marker of multiple sclerosis spinal cord pathology?
title_fullStr Neurite dispersion: A new marker of multiple sclerosis spinal cord pathology?
title_full_unstemmed Neurite dispersion: A new marker of multiple sclerosis spinal cord pathology?
title_short Neurite dispersion: A new marker of multiple sclerosis spinal cord pathology?
title_sort neurite dispersion a new marker of multiple sclerosis spinal cord pathology
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