CEST-based biomarkers to delimit the epileptic zone – CEST-Focus
Epilepsy is a common neurological disease, with 1% incidence and, despite multiple available anti-epileptic molecules, ~30% of the patients are drug-resistant. Brain surgery is an effective therapy for an important number of these patients. Intracerebral Stereo EEG (SEEG) is the method of choice to locate the surgical boundaries, especially in cases of absence of MRI-visible lesion or when noninvasive EEG pattern suggests that several or widespread epileptic networks could be at play. However, SEEG limitations are its invasiveness and limited brain volume sampling. Despite advances in neuroimaging techniques, improving the localization of the epileptic zone (EZ) and mapping of brain functional alterations beyond macroscopic MRI defects is still an unmet need. Because epileptic tissues are characterized by an increased excitatory drive and metabolic defects, techniques allowing a precise assessment of these alterations would deepen our knowledge of the disease.
An alternative MRI approach, based on glutamate quantification with Chemical Exchange Saturation Transfer (CEST) was suggested to help localize the EZ, although the limited availability of ultra-high field MR scanners, the low precision in EZ localization, and the lack of a systematic validation on patients have impeded its clinical use. In this project, we will (WP1) advance the use of CEST MRI to localize the epileptic zone in animal models and (WP2) apply our findings on a cohort of patients candidates for surgery. We will quantify glutamate and glucose concentration with Glu- and GlucoCEST respectively, in two mice models of epilepsy (Temporal Lobe Epilepsy – TLE, and genetic) and TLE patients. Animal models will provide us with the fingerprint of different epileptic phenotypes (e.g., lesional or not) for cellular and molecular features. Data collected in patients, informed by multimodal essays on animal models, will directly integrate into clinical care protocols.
Monsieur Davide BOIDO (Institut des sciences du vivant FRÉDÉRIC-JOLIOT)
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
IGF Institut de Génomique Fonctionnelle
JOLIOT Institut des sciences du vivant FRÉDÉRIC-JOLIOT
IPMC Institut de pharmacologie moléculaire et cellulaire
Rothschild Medical Development
Help of the ANR 552,659 euros
Beginning and duration of the scientific project: December 2022 - 36 Months