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

Hans Peter Müller, Martin R. Turner, Julian Grosskreutz, Sharon Abrahams, Peter Bede, Varan Govind, Johannes Prudlo, Albert C. Ludolph, Massimo Filippi, Jan Kassubek, Neuroimaging Society in ALS (NiSALS) DTI Study Group, Vincenzo Silani

Research output: Contribution to journalArticle

Abstract

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 ALS-specialist 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 DTI-based metrics as read-out in natural history, prognostic stratification and multisite disease-modifying studies in ALS.

Original languageEnglish
Pages (from-to)570-9
Number of pages10
JournalJournal of Neurology, Neurosurgery and Psychiatry
Volume87
Issue number6
DOIs
Publication statusPublished - Jun 2016

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Diffusion Tensor Imaging
Amyotrophic Lateral Sclerosis
Anisotropy
Efferent Pathways
Pyramidal Tracts
Dermatoglyphics
Frontal Lobe
Natural History
Sample Size
Brain Stem
Multicenter Studies
Retrospective Studies
Biomarkers
Equipment and Supplies

Keywords

  • Journal Article

Cite this

A large-scale multicentre cerebral diffusion tensor imaging study in amyotrophic lateral sclerosis. / Müller, Hans Peter; Turner, Martin R.; Grosskreutz, Julian; Abrahams, Sharon; Bede, Peter; Govind, Varan; Prudlo, Johannes; Ludolph, Albert C.; Filippi, Massimo; Kassubek, Jan; Neuroimaging Society in ALS (NiSALS) DTI Study Group ; Silani, Vincenzo.

In: Journal of Neurology, Neurosurgery and Psychiatry, Vol. 87, No. 6, 06.2016, p. 570-9.

Research output: Contribution to journalArticle

Müller, HP, Turner, MR, Grosskreutz, J, Abrahams, S, Bede, P, Govind, V, Prudlo, J, Ludolph, AC, Filippi, M, Kassubek, J, Neuroimaging Society in ALS (NiSALS) DTI Study Group & Silani, V 2016, 'A large-scale multicentre cerebral diffusion tensor imaging study in amyotrophic lateral sclerosis', Journal of Neurology, Neurosurgery and Psychiatry, vol. 87, no. 6, pp. 570-9. https://doi.org/10.1136/jnnp-2015-311952
Müller, Hans Peter ; Turner, Martin R. ; Grosskreutz, Julian ; Abrahams, Sharon ; Bede, Peter ; Govind, Varan ; Prudlo, Johannes ; Ludolph, Albert C. ; Filippi, Massimo ; Kassubek, Jan ; Neuroimaging Society in ALS (NiSALS) DTI Study Group ; Silani, Vincenzo. / A large-scale multicentre cerebral diffusion tensor imaging study in amyotrophic lateral sclerosis. In: Journal of Neurology, Neurosurgery and Psychiatry. 2016 ; Vol. 87, No. 6. pp. 570-9.
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AU - Müller, Hans Peter

AU - Turner, Martin R.

AU - Grosskreutz, Julian

AU - Abrahams, Sharon

AU - Bede, Peter

AU - Govind, Varan

AU - Prudlo, Johannes

AU - Ludolph, Albert C.

AU - Filippi, Massimo

AU - Kassubek, Jan

AU - Neuroimaging Society in ALS (NiSALS) DTI Study Group

AU - Silani, Vincenzo

N1 - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

PY - 2016/6

Y1 - 2016/6

N2 - 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 ALS-specialist 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 DTI-based metrics as read-out in natural history, prognostic stratification and multisite disease-modifying studies in ALS.

AB - 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 ALS-specialist 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 DTI-based metrics as read-out in natural history, prognostic stratification and multisite disease-modifying studies in ALS.

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