In vivo GABA increase as a biomarker of the epileptogenic zone: an unbiased metabolomics approach
Florence Fauvelle1,2, Vasile Stupar1,2, Jia Guo3, Wafae Labriji1, Chen Liu3, Alicia Plaindoux1, Emmanuel Luc Barbier1,2, Sophie Hamelin1, and Antoine Depaulis1
1Grenoble Institut Neurosciences, University Grenoble Alpes, La Tronche, France, 2IRMaGE, University Grenoble Alpes, La Tronche, France, 3Departement of Psychiatry, Columbia University, New York, NY, United States
Using ex vivo NMR spectroscopy-based (MRS)
untargeted metabolomics and in vivo
edition-MRS method, we demonstrated that GABA was a robust in vivo biomarker of epileptogenic zone in mesio-temporal lobe
epilepsy.
Figure
3: A/ In vivo GABA edition using MEGA-PRESS pulse sequence. Examples of
GABA and GLX peaks in the subtracted spectrum, fitted using the JET algorithm,
in Sham (top) and KA-MTLE (bottom) mice (regular KA dose). B/ Regression curve
between in vivo GABA+/GLX and ex vivo GABA/GLX
Figure
2: A/ Score plot of the principal
component analysis (PCA) built with HRMAS MRS data of KA-MTLE mice and the 5
brain regions sampled (ipsilateral and contralateral hippocampus (IH and CH), posterior (P) and anterior (A), and adjacent cortex) . B/ Variable importance in the projection (VIP) ranking
metabolites from most discriminative (VIP>1) to less discriminative ones in
KA-MTLE mice C/ Percentage of variation of 8 metabolites (among the 19
metabolites quantified) in the 5 brain regions of KA-MTLE mice vs their sham
homologous.