Mapping GABA+/Glx in experimental temporal lobe epilepsy using edited-MRSI at 9.4T.

Area of Science:

• Neuroscience
• Medical Imaging
• Epilepsy Research

Background:

• Mesial temporal lobe epilepsy (MTLE) is a common drug-resistant form of epilepsy.
• Accurate spatial localization of the epileptogenic zone (EZ) is crucial for successful epilepsy surgery, but remains challenging.
• Previous research identified increased gamma-aminobutyric acid (GABA) and decreased Glx (Glutamate + glutamine) in the EZ, proposing the GABA/Glx ratio as a biomarker.

Purpose of the Study:

• To develop and validate a non-invasive Magnetic Resonance Spectroscopy (MRS) method for improved spatial localization of the EZ in MTLE.
• To introduce and assess an original GABA-edited Magnetic Resonance Spectroscopic Imaging (MRSI) method, MEGA-LASER CSI, for mapping GABA and Glx.

Main Methods:

• Development and validation of the MEGA-LASER CSI sequence using multi-compartment phantoms with varying GABA concentrations.
• Application of the MRSI method in pre-clinical settings to map GABA and Glx in vivo.
• Correlation of in vivo findings with ex vivo data and preliminary immunohistochemistry.

Main Results:

• The MEGA-LASER CSI sequence demonstrated high accuracy in spatially discriminating GABA concentrations in phantoms.
• In vivo experiments revealed a significantly increased GABA+/Glx ratio in the EZ of epileptic animals compared to controls.
• Preliminary immunohistochemistry suggested astrocytic localization of GAD65 in the EZ, indicating a potential shift in GABA synthesis.

Conclusions:

• The developed MEGA-LASER CSI method and processing pipeline enable accurate non-invasive mapping of GABA and Glx.
• The increased GABA+/Glx ratio in the EZ is confirmed in vivo, supporting its role as a potential biomarker.
• This workflow is suitable for neuroscience and pre-clinical applications, potentially aiding in the localization of the EZ for epilepsy surgery.