title: Study-level wavelet cluster analysis and data-driven signal models in pharmacological MRI.
abstract: In pharmacological MRI (phMRI) studies tracking signal changes following the acute administration of a compound, the spatiotemporal pattern of response is often unknown a priori. Moreover, when analysed within a general linear model (GLM) framework, the experimental paradigm of a single injection point under-informs the construction of an appropriate signal model, and information from pharmacokinetics or ancillary in vivo studies may be unavailable or insufficient to accurately describe the dynamic signal changes observed following injection of the drug. Here, we extend the application of a data-driven clustering algorithm, wavelet cluster analysis (WCA), to phMRI data from one or more groups of subjects in a study. A WCA decomposition of spatially concatenated time series' provides a compact overview of spatiotemporal response patterns across cohorts, highlighting typical temporal signatures, brain regions implicated in the response and inter-subject variability. Further, we demonstrate the use of regressors based on selected temporal components as suitable signal models in GLM-based analyses, resulting in a close fit to dynamic phMRI signal changes. This approach is illustrated with simulated data and two representative in vivo phMRI studies in the rat (nicotine and apomorphine challenges).
authors.affiliation: Department of Neuroimaging, Psychiatry Centre of Excellence in Drug Discovery, GlaxoSmithKline Medicines Research Centre, Via Fleming 4, 37135 Verona, Italy. adam.j.schwarz@gsk.com
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Schwarz
authors.forename: Brandon
authors.initials: B
authors.lastname: Whitcher
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gozzi
authors.forename: Torsten
authors.initials: T
authors.lastname: Reese
authors.forename: Angelo
authors.initials: A
authors.lastname: Bifone
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000493:pharmacokinetics; D016477:Artifacts; D001921:Brain / Q000187:drug effects*; D016000:Cluster Analysis; D003198:Computer Simulation; D018491:Dopamine Agonists / Q000493:pharmacokinetics; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008954:Models, Biological; D009538:Nicotine / Q000493:pharmacokinetics*; D018722:Nicotinic Agonists / Q000493:pharmacokinetics*; D051381:Rats; D012815:Signal Processing, Computer-Assisted
chemical_list: D018491:Dopamine Agonists; D018722:Nicotinic Agonists; D009538:Nicotine; D001058:Apomorphine