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 ultrashort 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.
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 846793”.
Staff and Collaborators
- Bednařík P, Henry PG, Khowaja A, Rubin N, Kumar A, Deelchand D, Eberly LE, Seaquist E, Öz G, Moheet A. Hippocampal Neurochemical Profile and Glucose Transport Kinetics in Patients With Type 1 Diabetes. J Clin Endocrinol Metab. 2020 Feb 1;105(2). doi: 10.1210/clinem/dgz062.
- Bednarik P, Spurny B, Silberbauer L, Svatkova A, Handschuh P, Reiter B, Konadu M, Stimpfl T, Spies M, Bogner W, Lanzenberger R. Effect of ketamine on human neurochemistry in posterior cingulate cortex: A pilot magnetic resonance spectroscopy study at 3 Tesla. Frontiers in Neuroscience. Section Neuropharmacology.
- Bednarik P, Goranovic D, Svatkova A, Niess F, Hingerl L , Strasser B, Deelchand D, Spurny-Dworak B, Trattnig S, Hangel G, Scherer T, Lanzenberger R, Bogner W. Deuterium labeling enables non-invasive 3D proton MR imaging of glucose and neurotransmitter metabolism in the human brain. Nature Biomed Eng. [under review]
- Horak T, Horakova M, Svatkova A, Kadanka Z Jr., Kudlicka P, Valosek J, Rohan T, Kerkovsky M, Vlckova E, Kadanka Z, Deelchand D, Henry PG, Bednarik J, Bednarik P. In vivo molecular signatures of cervical spinal cord pathology in degenerative compression. Journal of Neurotrauma
- Gröhn H, Gillick BT, Tkáč I, Bednařík P, Mascali D, Deelchand DK, Michaeli S, Meekins GD, Leffler-McCabe MJ, MacKinnon CD, Eberly LE, Mangia S. Influence of Repetitive Transcranial Magnetic Stimulation on Human Neurochemistry and Functional Connectivity: A Pilot MRI/MRS Study at 7 T. Front Neurosci. 2019;13:1260. doi: 10.3389/fnins.2019.01260.
- Silberbauer LR, Spurny B, Handschuh P, Klöbl M, Bednarik P, Reiter B, Ritter V, Trost P, Konadu ME, Windpassinger M, Stimpfl T, Bogner W, Lanzenberger R, Spies M. Effect of Ketamine on Limbic GABA and Glutamate: A Human In Vivo Multivoxel Magnetic Resonance Spectroscopy Study. Front Psychiatry. 2020;11:549903. doi: 10.3389/fpsyt.2020.549903
- Valosek J, Labounek R, Horak T, Horakova M, Bednarik P, Kerkovsky M, Kocica J, Rohan T, Lenglet C, Cohen-Adad J, Hlustik P, Vlckova E, Kadanka Z, Bednarik J, Svatkova A. Diffusion magnetic resonance imaging reveals tract-specific microstructural correlates of electrophysiological impairments in non-myelopathic and myelopathic spinal cord compression. Eur J Neurol. 2021 Nov;28(11):3784-3797. doi: 10.1111/ene.15027. Epub 2021 Aug 4.
- Horáková M, Horák T, Valošek J, Rohan T, Koriťáková E, Dostál M, Kočica J, Skutil T, Keřkovský M, Kadaňka Z Jr., Bednařík P, Svátková A, Hluštík P, Bednařík J. Semi-automated detection of cervical spinal cord compression with the Spinal Cord Toolbox. Quantitative Imaging in Medicine and Surgery. [under review]
- Bednarik P, Goranovic D, Hingerl L, Svatkova A, Niess N, Mlynarik V, Deelchand D, Scherer T, Lanzenberger R, Bogner W .Deuterium labeling enables noninvasive 3D proton MR imaging of glucose metabolism and neurotransmission in humans. Minnesota spectroscopy worshop 2021. Early Career Poster Award.
- Bednarik P., Hingerl L., Goranovic D., Svatkova A., de Lima Cardoso P., Trattnig S., Lanzenberger R., Bogner W. Functional spectroscopic imaging (fMRSI) detects metabolite changes in the activated primary sensorimotor cortex at 7T, ISMRM 2020. ISMRM Merit Award: Summa cum laude.
- Bednarik, P et al. Feasibility of functional spectroscopy on a clinical (3T) scanner, ESMRMB 2019, 36th Annual Scientific Meeting, Rotterdam, NL, October 3–October 5: Abstracts, Friday. Magn. Reson. Mater. Physics, Biol. Med. 32, 107–233 (2019).
- Svatkova, A, Minarikova L, Bednarik, P, Rosenmayr V, Hangel, G, Strasser B, Hingerl, L, Stulnig T, Gruber S. Metabolic and microstructural MPSII brain alteration revealed by multiparametric MR imaging and spectroscopy – a combined 3T and 7T study, in ISMRM, 2020
Awards and Distinctions
- NARSAD Young Investigator Award (grant no. 27238) from the Brain and Behaviour Research Foundation (2018)
- ISMRM Merit Award 2020: Summa cum Laude (awarded peer-reviewed talk)
- Early Career Poster Award: CMRR High-filed workshop 2021 at the University of Minnesota