title: A large-scale multicentre cerebral diffusion tensor imaging study in amyotrophic lateral sclerosis.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Neurology, University of Ulm, Ulm, Germany.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Müller
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Turner
authors.affiliation: Hans-Berger Department of Neurology, Jena University Hospital, Jena, Germany.
authors.forename: Julian
authors.initials: J
authors.lastname: Grosskreutz
authors.affiliation: Human Cognitive Neuroscience, Psychology-PPLS & Euan MacDonald Centre for MND Research & Centre for Cognitive Ageing and Epidemiology, University of Edinburgh, Edinburgh, UK.
authors.forename: Sharon
authors.initials: S
authors.lastname: Abrahams
authors.affiliation: Quantitative Neuroimaging Group, Academic Unit of Neurology, Trinity College Dublin, Dublin, Ireland.
authors.forename: Peter
authors.initials: P
authors.lastname: Bede
authors.affiliation: Department of Radiology, University of Miami School of Medicine, Miami, Florida, USA.
authors.forename: Varan
authors.initials: V
authors.lastname: Govind
authors.affiliation: Department of Neurology, University of Rostock and DZNE, Rostock, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Prudlo
authors.affiliation: Department of Neurology, University of Ulm, Ulm, Germany.
authors.forename: Albert C
authors.initials: AC
authors.lastname: Ludolph
authors.affiliation: Division of Neuroscience, Neuroimaging Research Unit, Institute of Experimental Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
authors.affiliation: Department of Neurology, University of Ulm, Ulm, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Kassubek
mesh_terms: D000465:Algorithms; D000690:Amyotrophic Lateral Sclerosis / Q000000981:diagnostic imaging*; D015415:Biomarkers; D001921:Brain / Q000000981:diagnostic imaging*; D015331:Cohort Studies; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000000981:diagnostic imaging*; D011379:Prognosis; D012189:Retrospective Studies; D066127:White Matter / Q000000981:diagnostic imaging*
chemical_list: D015415:Biomarkers