A large-scale multicentre cerebral diffusion tensor imaging study in amyotrophic lateral sclerosis

Objective Damage to the cerebral tissue structural connectivity associated with amyotrophic lateral sclerosis (ALS), which extends beyond the motor pathways, can be visualised by diffusion tensor imaging (DTI). The effective translation of DTI metrics as biomarker requires its application across mul...

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Main Authors: Müller, H, Turner, M, Grosskreutz, J, Abrahams, S, Bede, P, Govind, V, Prudlo, J, Ludolph, A, Filippi, M, Kassubek, J
Format: Journal article
Published: BMJ Publishing Group 2016
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author Müller, H
Turner, M
Grosskreutz, J
Abrahams, S
Bede, P
Govind, V
Prudlo, J
Ludolph, A
Filippi, M
Kassubek, J
author_facet Müller, H
Turner, M
Grosskreutz, J
Abrahams, S
Bede, P
Govind, V
Prudlo, J
Ludolph, A
Filippi, M
Kassubek, J
author_sort Müller, H
collection OXFORD
description Objective Damage to the cerebral tissue structural connectivity associated with amyotrophic lateral sclerosis (ALS), which extends beyond the motor pathways, can be visualised by diffusion tensor imaging (DTI). The effective translation of DTI metrics as biomarker requires its application across multiple MRI scanners and patient cohorts. A multicentre study was undertaken to assess structural connectivity in ALS within a large sample size. Methods 442 DTI data sets from patients with ALS (N=253) and controls (N=189) were collected for this retrospective study, from eight international ALSspecialist clinic sites. Equipment and DTI protocols varied across the centres. Fractional anisotropy (FA) maps of the control participants were used to establish correction matrices to pool data, and correction algorithms were applied to the FA maps of the control and ALS patient groups. Results Analysis of data pooled from all centres, using whole-brain-based statistical analysis of FA maps, confirmed the most significant alterations in the corticospinal tracts, and captured additional significant white matter tract changes in the frontal lobe, brainstem and hippocampal regions of the ALS group that coincided with postmortem neuropathological stages. Stratification of the ALS group for disease severity (ALS functional rating scale) confirmed these findings. Interpretation This large-scale study overcomes the challenges associated with processing and analysis of multiplatform, multicentre DTI data, and effectively demonstrates the anatomical fingerprint patterns of changes in a DTI metric that reflect distinct ALS disease stages. This success paves the way for the use of DTIbased metrics as read-out in natural history, prognostic stratification and multisite disease-modifying studies in ALS.
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spelling oxford-uuid:7a7d4a8d-3588-464c-b672-c34498ab17a32022-03-26T20:44:26ZA large-scale multicentre cerebral diffusion tensor imaging study in amyotrophic lateral sclerosisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7a7d4a8d-3588-464c-b672-c34498ab17a3Symplectic Elements at OxfordBMJ Publishing Group2016Müller, HTurner, MGrosskreutz, JAbrahams, SBede, PGovind, VPrudlo, JLudolph, AFilippi, MKassubek, JObjective Damage to the cerebral tissue structural connectivity associated with amyotrophic lateral sclerosis (ALS), which extends beyond the motor pathways, can be visualised by diffusion tensor imaging (DTI). The effective translation of DTI metrics as biomarker requires its application across multiple MRI scanners and patient cohorts. A multicentre study was undertaken to assess structural connectivity in ALS within a large sample size. Methods 442 DTI data sets from patients with ALS (N=253) and controls (N=189) were collected for this retrospective study, from eight international ALSspecialist clinic sites. Equipment and DTI protocols varied across the centres. Fractional anisotropy (FA) maps of the control participants were used to establish correction matrices to pool data, and correction algorithms were applied to the FA maps of the control and ALS patient groups. Results Analysis of data pooled from all centres, using whole-brain-based statistical analysis of FA maps, confirmed the most significant alterations in the corticospinal tracts, and captured additional significant white matter tract changes in the frontal lobe, brainstem and hippocampal regions of the ALS group that coincided with postmortem neuropathological stages. Stratification of the ALS group for disease severity (ALS functional rating scale) confirmed these findings. Interpretation This large-scale study overcomes the challenges associated with processing and analysis of multiplatform, multicentre DTI data, and effectively demonstrates the anatomical fingerprint patterns of changes in a DTI metric that reflect distinct ALS disease stages. This success paves the way for the use of DTIbased metrics as read-out in natural history, prognostic stratification and multisite disease-modifying studies in ALS.
spellingShingle Müller, H
Turner, M
Grosskreutz, J
Abrahams, S
Bede, P
Govind, V
Prudlo, J
Ludolph, A
Filippi, M
Kassubek, J
A large-scale multicentre cerebral diffusion tensor imaging study in amyotrophic lateral sclerosis
title A large-scale multicentre cerebral diffusion tensor imaging study in amyotrophic lateral sclerosis
title_full A large-scale multicentre cerebral diffusion tensor imaging study in amyotrophic lateral sclerosis
title_fullStr A large-scale multicentre cerebral diffusion tensor imaging study in amyotrophic lateral sclerosis
title_full_unstemmed A large-scale multicentre cerebral diffusion tensor imaging study in amyotrophic lateral sclerosis
title_short A large-scale multicentre cerebral diffusion tensor imaging study in amyotrophic lateral sclerosis
title_sort large scale multicentre cerebral diffusion tensor imaging study in amyotrophic lateral sclerosis
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