title: Determination of drug-induced changes in functional MRI signal using a pharmacokinetic model.
abstract: As the applications of functional magnetic resonance imaging (fMRI) expand, there is a need for the development of new strategies for data extraction and analysis that do not require the presentation of stimuli in a repeated on/off pattern. A description and evaluation of a method and computer algorithm for the detection and analysis of brain activation patterns following acute drug administration using fMRI are presented. A waveform analysis protocol (WAP) input function has been developed that is based upon the single-dose pharmacokinetics of a drug of interest. As a result of this analysis, regional brain activation can be characterized by its localization and intensity of activation, onset of action, time to peak effect, and duration of action. A global statistical test for significant drug effects based upon the probability of a voxel being activated by a saline vehicle injection is applied to grouped data on a voxel by voxel basis. Representative data are presented using nicotine as a prototypical agent. Using this method, statistically significant drug-induced brain activation has been identified in several key cortical and subcortical brain regions.
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226, USA. abloom@mcw.edu
authors.forename: A S
authors.initials: AS
authors.lastname: Bloom
authors.forename: R G
authors.initials: RG
authors.lastname: Hoffmann
authors.forename: S A
authors.initials: SA
authors.lastname: Fuller
authors.forename: J
authors.initials: J
authors.lastname: Pankiewicz
authors.forename: H H
authors.initials: HH
authors.lastname: Harsch
authors.forename: E A
authors.initials: EA
authors.lastname: Stein
mesh_terms: D000328:Adult; D000465:Algorithms; D001921:Brain / Q000187:drug effects* / Q000502:physiology*; D003198:Computer Simulation; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging; D008959:Models, Neurological; D009538:Nicotine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*
chemical_list: D009538:Nicotine