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Abstract #4387

Qualification of in vivo 1H MRS as a Quantitative Preclinical Tool for Evaluating Drug Efficacy in Pharma Research

Conny F. Waschkies1, 2, Stephanie Schppenthau2, Andreas Bruns2, Thomas Bielser2, Markus von Kienlin2, Markus Rudin1, Basil Knnecke2

1Institute for Biomedical Engineering, ETH and University Zurich, Zurich, Switzerland; 2Magnetic Resonance Imaging & Spectroscopy, F. Hoffmann-La Roche, Basel, Switzerland

We have qualified preclinical 1H MRS as sensitive readout of changes in major neurotransmitters for its use in pharma discovery in psychiatric disorders. (i) Generic sensitivity of 1H MRS was assessed under our conditions in routine operation by way of a prospective power analysis in order to estimate the smallest changes reliably detectable. (ii) Pharmacological relevance was demonstrated by establishing dose-response relationships upon various pharmacological interventions and by corroborative evidence obtained with standard ex vivo biochemistry methods. (ii) Biological significance was demonstrated by unveiling region-specific differences in basal neurotransmitter levels and function-specific regional responses to pharmacological modulations.