EPINOV “Improving EPIlepsy surgery management and progNOsis using Virtual brain technology”

Thousands of patients with Drug Resistant focal Epilepsy (DRE) undergo resective brain surgery with the aim of achieving seizure freedom. Despite technical advances, the success rate of epilepsy surgery in terms of seizure freedom has not greatly improved, remaining at around 50%. Epilepsy surgical failure can be due to the non-resection or insufficient modulation of the important nodes and pathways that characterize the epileptogenic network. For any candidate for epilepsy surgery, the critical factor in deciding upon the treatment strategy is the correct estimation of surgery outcome. No reliable procedure currently exists to combine the various prognostic factors for a given patient. This leads to great uncertainty on an individual scale in predicting the effects of surgery.

The EPINOV project is one of 10 large-scale projects selected in the 3rd wave of the French scientific excellence call entitled « Recherche Hospitalo-Universitaire en santé » (RHU) operated by the National Research Agency (ANR). This work is supported by a public grant from the second “Investissements d’Avenir” program (reference: ANR-17-RHUS-0004). This project relies on an innovative approach with the goal of understanding epileptic networks and the definition of optimal treatment strategies at the individual level, by using large–scale brain modelling.

Project in numbers

• Launching date : January 2018

• Duration : 5 years

• Total ANR contribution : 5,8M€

OBJECTIVES

The main objective of EPINOV project is to improve epilepsy surgical prognosis through clinical, technical and commercial means using Virtual Brain technology. It aims to significantly improve accuracy of SEEG and presurgical interpretation and guide surgical strategies by introducing a scientifically-validated and clinically-tested method for more precise and accurate mapping of epileptic networks in patients with drug resistant epilepsy (DRE).

• Validate the Virtual Brain method in a prospective multi-centric clinical trial in the largest epilepsy reference centers (10 major public hospitals) in France. This will constitute the largest patient cohort (>300 patients) worldwide using this kind of approach.

• Develop a clinically-validated pipeline which will provide clinicians a patient-specific epileptogenicity map of the most epileptogenic brain areas as targets for resective surgery.

• Provide a virtual brain-based simulation software prototype allowing clinicians to improve the identification of the epileptogenic zone and better plan the surgical strategies.

• Reduce comorbidities and improve the quality of life of DRE patients by refining the epilepsy surgery indications, improving the surgical strategies and integrating the individualized brain modeling in the clinical practice.

METHODS

The Virtual Brain is a modeling technology comprising a dynamic network model of the human adult brain. The functions of the brain model are constrained by personalized human anatomical information derived from non-invasive brain imaging. Personalized modeled data generated by TVB will improve accuracy of localisation of the epileptogenic zone, guide optimal surgical strategy and improve surgery outcome. The prospective, randomized trial will include subjects with DRE who undergo presurgical evaluation and surgical decision-making will be taken in multidisciplinary patient management conferences.

In the virtualized group, detailed patient anatomy, structural connectivity and SEEG will serve as input for the virtual patient (VEP). An individualized VEP report indicating the most epileptogenic regions will be provided to each investigator. Surgical decision will be made by multidisciplinary patient management conferences considering the VEP results. We will compare: 1 | surgical outcome at 1 year in terms of seizure frequency, 2 | influence of VEP results on surgical strategies and surgical morbidity.

VEP will also be performed retrospectively in operated patients from the control group and the results of the virtualization will be compared to the actual surgery outcome. We will work towards translating these technologies to the market, which will revolutionize the management of epilepsy surgical candidates and improve prognosis of epilepsy surgery.

PUBLICATIONS

Selected publications

1. Wang HE, et al. (2021) “VEP atlas: An anatomic and functional human brain atlas dedicated to epilepsy patients” (Journal of Neuroscience Methods)

2. Makhalova J, et al. (2022) “Virtual epileptic patient brain modeling: Relationships with seizure onset and surgical outcome“ (Epilepsia)

3. Azilinon M, et al. (2023) “Combining sodium MRI, proton MR spectroscopic imaging, and intracerebral EEG in epilepsy“ (Human Brain Mapping)

4. Coelli S, et al. (2023) “Comparison of beamformer and ICA for dynamic connectivity analysis: A simultaneous MEG-SEEG study“ (NeuroImage)

NEWS

PROJECT PARTNERS

The EPINOV project relies on a public-private partnership coordinated by an academic Institution, Aix-Marseille University (AMU) and composed of a public research institution, the French Institute of Health and Medical Research (NSERM) an industrial partner, Dassault Systèmes (3DS) and two public health establishments, the Assistance-Publique Hôpitaux de Marseille (AP-HM) and the Hospices Civils de Lyon (HCL).

CONTACT INFORMATION

Scientific Coordinator of EPINOV Project : Prof. Fabrice BARTOLOMEI, head of the department of Epileptology and Cerebral Rhythmology, La Timone, AP-HM.