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

Research output: Contribution to journalArticle

57 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)570-579
Number of pages10
JournalJournal of Neurology, Neurosurgery and Psychiatry
Volume87
Issue number6
DOIs
Publication statusPublished - Jun 1 2016

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

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Surgery
  • Arts and Humanities (miscellaneous)

Cite this

Müller, H. P., Turner, M. R., Grosskreutz, J., Abrahams, S., Bede, P., Govind, V., ... Kassubek, J. (2016). A large-scale multicentre cerebral diffusion tensor imaging study in amyotrophic lateral sclerosis. Journal of Neurology, Neurosurgery and Psychiatry, 87(6), 570-579. https://doi.org/10.1136/jnnp-2015-312882

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.

In: Journal of Neurology, Neurosurgery and Psychiatry, Vol. 87, No. 6, 01.06.2016, p. 570-579.

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 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. 570-579. https://doi.org/10.1136/jnnp-2015-312882
Müller, Hans Peter ; Turner, Martin R. ; Grosskreutz, Julian ; Abrahams, Sharon ; Bede, Peter ; Govind, Varan ; Prudlo, Johannes ; Ludolph, Albert C. ; Filippi, Massimo ; Kassubek, Jan. / 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. 570-579.
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