"Domain gauges": A reference system for multivariate profiling of brain fMRI activation patterns induced by psychoactive drugs in rats

NeuroImage
Andreas BrunsMarkus von Kienlin

Abstract

Pharmacological magnetic resonance imaging (phMRI) of the brain has become a widely used tool in both preclinical and clinical drug research. One of its challenges is to condense the observed complex drug-induced brain-activation patterns into semantically meaningful metrics that can then serve as a basis for informed decision making. To aid interpretation of spatially distributed activation patterns, we propose here a set of multivariate metrics termed "domain gauges", which have been calibrated based on different classes of marketed or validated reference drugs. Each class represents a particular "domain" of interest, i.e., a specific therapeutic indication or mode of action. The drug class is empirically characterized by the unique activation pattern it evokes in the brain-the "domain profile". A domain gauge provides, for any tested intervention, a "classifier" as a measure of response strength with respect to the domain in question, and a "differentiator" as a measure of deviation from the domain profile, both along with error ranges. Capitalizing on our in-house database with an unprecedented wealth of standardized perfusion-based phMRI data obtained from rats subjected to various validated treatments, we exemplarily focu...Continue Reading

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Citations

Apr 16, 2016·Scientific Reports·Marija M PetrinovicThomas Mueggler
Mar 8, 2018·Scientific Reports·Juergen DukartFabio Sambataro
Jun 10, 2017·Frontiers in Cellular Neuroscience·Allison L McIntoshAndrew Harkin
Apr 7, 2017·Psychopharmacology·Kristoffer SahlholmAileen Schroeter
Nov 6, 2015·Frontiers in Pharmacology·Elisabeth JonckersAnnemie Van der Linden
Jun 1, 2021·Frontiers in Neuroinformatics·Michel DojatEmmanuel L Barbier
May 19, 2021·European Journal of Radiology·Liesbeth RenemanElsmarieke van de Giessen
Jan 18, 2020·Journal of Medicinal Chemistry·Patrick SchniderChristophe Grundschober

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