Descrizione del progetto
Uno strumento non invasivo per monitorare l’efficacia degli antidepressivi
La ketamina è un anestetico approvato che viene utilizzato anche come farmaco contro la depressione resistente ai trattamenti. Sebbene funga da antagonista ai recettori per il glutammato presenti nel cervello, i suoi meccanismi regolatori precisi sono tuttora sconosciuti. Per affrontare tale questione, il progetto GLU-IMAGE, finanziato dall’UE, ha elaborato un metodo di immaginografia per monitorare i cambiamenti di piccola entità nei livelli di glutammato del cervello in un modo non invasivo. La sensibilità di questo metodo ne agevola l’applicazione clinica per stimare le concentrazioni di glutammato in risposta alla somministrazione di ketamina in pazienti affetti da depressione. Inoltre, può essere utilizzato per determinare l’efficacia di altre terapie glutammatergiche.
Obiettivo
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.
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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
1090 Wien
Austria