Project description DEENESFRITPL A non-invasive tool for monitoring antidepressant efficacy Ketamine is an approved anaesthetic that is also used as medication against treatment-resistant depression. Although it acts as an antagonist to glutamate receptors in the brain, the precise mechanism remains unknown. To address this issue, the EU-funded GLU-IMAGE project has developed an imaging method for monitoring small changes in glutamate levels in the brain in a non-invasive manner. The sensitivity of the method facilitates its clinical application to estimate glutamate concentrations in response to ketamine administration in patients with depression. Moreover, it can be utilised to determine the efficacy of other glutamatergic therapeutics. Show the project objective Hide the project objective Objective While clinical experience confirmed ketamine, a glutamate (Glu) N-methyl-D-aspartate receptor antagonist, as a potent therapy of treatment-resistant major depressive disorder (TRD), the exact mechanism of ketamine’s action in the brain is unclear. Thus, a method to reliably and reproducibly monitor minute changes in Glu metabolism in the human brain is urgently needed to understand ketamine dynamics in vivo. So far, the pioneering work at the Medical University Vienna (MUW) showed ketamine-induced increase of vascular and metabolic responses measured as blood oxygenation level dependent (BOLD) signals in healthy subjects in thalamus, insula and anterior cingulate cortex (ACC), while others observed elevated glucose uptake using positron emission tomography, suggesting higher energetic demands and Glu response after ketamine infusion. Yet, a reliable and non-invasive method for direct monitoring of pharmacologically-induced dynamic Glu changes is still missing. Our group at MUW has recently developed a novel ground-breaking accelerated method for ultra-short echo time MRS imaging (UTE-MRSI) providing optimal Glu measures with critical sensitivity improvements compared to conventional proton single-voxel MRS (SV-MRS) and previously utilized MRSI approaches. Our method allows monitoring of Glu responses selectively in activated voxels and overcomes low spatial resolution, and limited coverage of SV-MRS that is the current gold standard for measurement of Glu concentrations and its dynamic changes in vivo (functional SV-MRS). The further improvement of UTE-MRSI by the implementation of the novel real-time motion correction will boost its applicability in clinical human studies. Thus, our UTE-MRSI will offer image-based multi-slice measurements of baseline Glu concentrations and its responses to ketamine administration with the potential to clarify ketamine’s mechanism of action in patients with TRD, and will allow monitoring of other novel glutamatergic therapies. Fields of science medical and health sciencesbasic medicinepharmacology and pharmacypharmacokineticsengineering and technologymedical engineeringdiagnostic imaging Keywords ultrahigh field neuroimaging magnetic resonance spectroscopic imaging magnetic resonance spectroscopy glutamate functional spectroscopy visual stimulation ketamine depression Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2018 - Individual Fellowships Call for proposal H2020-MSCA-IF-2018 See other projects for this call Funding Scheme MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinator MEDIZINISCHE UNIVERSITAET WIEN Net EU contribution € 186 167,04 Address SPITALGASSE 23 1090 Wien Austria See on map Region Ostösterreich Wien Wien Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 186 167,04
