Untersuchung glutamaterger Störungen bei depressiven Patienten anhand STEAM MRS im Hochmagnetfeld

Advances in Magnetic Resonance (MR) neuroimaging tools have greatly contributed to recent developments in the understanding of biological processes in psychiatric diseases such as Major Depressive Disorder. Using functional MRI (fMRI), a subset of specific brain regions that experience characteristic alterations of brain responses during well-delineated psychological conditions have been identified. While some consistencies were found with structural MR assessments and postmortem studies, the molecular basis of these alterations is largely unknown. This is due, primarily, to the inherent technical difficulties encountered in the leading non-invasive imaging technique available: Magnetic Resonance Spectroscopy (MRS). In animal models, and postmortem studies in humans, deficiencies in specific cellular targets within the glutamatergic system, e.g. the glial glutamate re-uptake from the synaptic cleft and its subsequent conversion to glutamine, have been reported. Such glutamatergic origins of dysfunction are further supported by pharmacological evidence of the beneficial effects of glutamate-modulating agents in depression, suggesting treatment-related changes of metabolite levels in a subset of regions. Further systematic investigations in psychiatric neuroimaging studies are primarily hindered by technical limitations resulting in an inability to discern glutamate and glutamine in MR-spectra at field strengths of up to 3 Tesla. Recent single-voxel solutions to circumvent the lack of sufficient line separation resulted in relatively large voxels that had to be measured for up to 20 minutes to obtain reliable metabolite separation. Studies to date were thus unable to systematically investigate brain regions with adequate resolution given the functional heterogeneity of key brain regions known from functional imaging studies. The long acquisition duration for each location further prevented investigations of regional specificity via assessments of a greater numbers of regions. Our project thus aims to develop an optimized MRS method to accomplish these goals using a STEAM-based sequence at ultra high field strength of 7 Tesla.