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.