title: The Neuro/PsyGRID calibration experiment: identifying sources of variance and bias in multicenter MRI studies.
abstract: Calibration experiments precede multicenter trials to identify potential sources of variance and bias. In support of future imaging studies of mental health disorders and their treatment, the Neuro/PsyGRID consortium commissioned a calibration experiment to acquire functional and structural MRI from twelve healthy volunteers attending five centers on two occasions. Measures were derived of task activation from a working memory paradigm, fractal scaling (Hurst exponent) from resting fMRI, and grey matter distributions from T(1) -weighted sequences. At each intracerebral voxel a fixed-effects analysis of variance estimated components of variance corresponding to factors of center, subject, occasion, and within-occasion order, and interactions of center-by-occasion, subject-by-occasion, and center-by-subject, the latter (since there is no intervention) a surrogate of the expected variance of the treatment effect standard error across centers. A rank order test of between-center differences was indicative of crossover or noncrossover subject-by-center interactions. In general, factors of center, subject and error variance constituted >90% of the total variance, whereas occasion, order, and all interactions were generally <5%. Subject was the primary source of variance (70%-80%) for grey-matter, with error variance the dominant component for fMRI-derived measures. Spatially, variance was broadly homogenous with the exception of fractal scaling measures which delineated white matter, related to the flip angle of the EPI sequence. Maps of P values for the associated F-tests were also derived. Rank tests were highly significant indicating the order of measures across centers was preserved. In summary, center effects should be modeled at the voxel-level using existing and long-standing statistical recommendations.
authors.affiliation: Department of Psychiatry & Behavioural and Clinical Neurosciences Institute, Brain Mapping Unit, University of Cambridge, Cambridge, UK. js369@cam.ac.uk
authors.forename: John
authors.initials: J
authors.lastname: Suckling
authors.forename: Anna
authors.initials: A
authors.lastname: Barnes
authors.forename: Dominic
authors.initials: D
authors.lastname: Job
authors.forename: David
authors.initials: D
authors.lastname: Brennan
authors.forename: Katherine
authors.initials: K
authors.lastname: Lymer
authors.forename: Paola
authors.initials: P
authors.lastname: Dazzan
authors.forename: Tiago Reis
authors.initials: TR
authors.lastname: Marques
authors.forename: Clare
authors.initials: C
authors.lastname: MacKay
authors.forename: Shane
authors.initials: S
authors.lastname: McKie
authors.forename: Steve R
authors.initials: SR
authors.lastname: Williams
authors.forename: Steven C R
authors.initials: SC
authors.lastname: Williams
authors.forename: Bill
authors.initials: B
authors.lastname: Deakin
authors.forename: Stephen
authors.initials: S
authors.lastname: Lawrie
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D015982:Bias; D001931:Brain Mapping; D002138:Calibration; D006801:Humans; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D015337:Multicenter Studies as Topic