Section: Partnerships and Cooperations

National Initiatives

Projet Fondation de France: PERINE: 99k€ (33 k€ for IRM acquisition and 22 k€ for image analysis) for 2011-2021

Participants : Élise Bannier, Isabelle Corouge, Julie Coloigner, Maia Proisy, Jean-Christophe Ferré, Christian Barillot.

The PELAGIE cohort evaluates the effect of prenatal exposure to neurotoxicants on child development. Following previous studies, the PERINE study focuses on the assessment of brain developement at 10-12 years old using MRI ( ASL, Diffusion imaging, Working memory as well as motor inhibition BOLD fMRI together with neuropsychological tests). A total of 101 children were included. A PhD of Anne-Claire Binter was defended in December 2019 linking epidemiology with functional imaging during a GoNoGo task and neuropsychological scores. This work is done in collaboration with Fabienne Pelé and Cécile Chevrier (IRSET).

Fondation de l’Avenir: EPMR-MA

Participants : Pierre-Yves Jonin, Élise Bannier, Christian Barillot, Quentin Duché.

Recognition memory refers to our ability to discriminate between previously experienced vs. unexperienced stimuli. It is impaired very early in the course of Alzheimer’s Disease (AD), both regarding behavioural performance and related brain activity. When the memoranda is associated or with existing knowledge, subsequent memory increases in healthy subjects. Moreover, existing knowledge related to prior exposures may alter the brain network underlying successful memory formation. While much is known regarding the brain substrates of recognition memory in early AD, little is known about the impact of prior exposure. Yet, this factor could both enhance memory formation in patients, and highlight a pattern of memory impairments and related brain activity that might accurately discriminates between early AD, before dementia, and healthy aging. The present task-based fMRI study aims at assessing the influence of prior exposures on recognition memory and its neural underpinnings in patients with Mild Cognitive Impairment due to AD. Inclusions were performed between 2016 and 2017 and data analysis is ongoing.

Projet Fondation de France: Connectivity of the amygdala in depression: (PI: M.-L. Paillère Martinot, Paris Descartes University), €200k for 2018-2021

Participants : Christian Barillot, Olivier Commowick, Emmanuel Caruyer, Julie Coloigner.

The onset of depression in teenagers and young adults increases the risk to develop a drug-resistant depression in the adulthood. This project aims at evaluating the role of early changes in the microstructure and connectivity of the amygdala. Using a cohort of drug-resistant patients (N=30), non drug-resistant patients (N=30) and controls (N=30), the aim is to identify imaging biomarkers of the pathology and to compare these with emotional and cognitive phenotypes in this population, searching for early differences in the development of the amygdala connectivity.

CNRS-Inserm Défi Santé numérique – AAP 2019: Imagerie Multimodale de l’Amygdale limbiquE pour le pronostic de la Dépression (IMpAirED): 19k€ for 2019

Participants : Julie Coloigner, Olivier Commowick, Élise Bannier, Emmanuel Caruyer, Christian Barillot.

This grant is an extension of the Projet Fondation de France: Connectivity of the amygdala in depression.

In order to identify early features of this depression disease, the aim of this project is to develop multimodal modeling of the limb amygdala and its network from MR imaging combining activation and rest functional imaging and MR brain microstructure imaging quantitative (diffusion and relaxometry). The development of this model will allow us to define three imaging biotypes corresponding to depressed adult patients responding to antidepressant treatments, depressed resistant patients and controls. These multimodal imaging biomarkers will be used to stratifie a large longitudinal cohort of young adults into three sub-groupsgroups, in order to retrospectively identify early differences in development trajectories of amygdala.

Inclusions of the patients will begin in early 2020.

ANR "MAIA", generic projects program: €150k for 2016-2019 (PI: F. Rousseau, IMT Atlantique, Brest)

Participants : Maia Proisy, Pierre Maurel, Antoine Legouhy, Olivier Commowick, Isabelle Corouge, Jean-Christophe Ferré, Christian Barillot.

Each year in France, 55 000 children are born prematurely, i.e., before the 37th week of gestation. Long-term studies of the outcome of prematurely born infants have clearly documented that the majority of such infants may have significant motor, cognitive, and behavioral deficits.

However, there is a limited understanding of the nature of the cerebral abnormality underlying these adverse neurologic outcomes. In this context, the emergence of new modalities of 3D functional MRI, e.g., Arterial Spin Labeling (ASL), or optical imaging technologies, e.g., Near InfraRed Spectroscopy (NIRS), brings new perspectives for extracting cognitive information, via metabolic activity measures. Other classical techniques devoted to cerebral signal measurement, such as ElectroEncephaloGraphy (EEG), provide cognitive information at the cortical level. Each of these various non-invasive imaging technologies brings substantial and specific information for the understanding of newborn brain development.

This project is developing innovative approaches for multi-image / multi-signal analysis, in order to improve neurodevelopment understanding methods. From a fundamental point of view, mathematics and computer science have to be considered in association with imaging physics and medicine, to deal with open issues of signal and image analysis from heterogeneous data (image, signal), considered in the multiphysics contexts related to data acquisition (magnetic, optic, electric signals) and biophysics modeling of the newborn brain. A sustained synergy between all these scientific domains is then necessary.

Finally, the sine qua non condition to reach a better understanding of the coupled morphological cognitive development of premature newborns, is the development of effective software tools, and their distribution to the whole medical community. The very target of this project is the design of such software tools for medical image / signal analysis, actually operational in clinical routine, and freely available. Academic researchers and industrial partners are working in close collaboration to reach that ambitious goal.

Fondation pour la recherche médicale (FRM) - Project Hybrid EEG/IRM Neurofeedback for rehabilitation of brain pathologies: 370k€ (2017-2021)

Participants : Élise Bannier, Isabelle Bonan, Isabelle Corouge, Jean-Christophe Ferré, Jean-Yves Gauvrit, Pierre Maurel, Mathis Fleury, Giulia Lioi, Christian Barillot.

The goal of this project is to make full use of neurofeedback (NF) paradigm in the context of brain rehabilitation. The major breakthrough will come from the coupling associating functional and metabolic information from Magnetic Resonance Imaging (fMRI) to Electro-encephalography (EEG) to “optimize” the neurofeedback protocol. We propose to combine advanced instrumental devices (Hybrid EEG and MRI platforms), with new hybrid Brain computer interface (BCI) paradigms and new computational models to provide novel therapeutic and neuro-rehabilitation paradigms in some of the major mental and neurological disorders of the developmental and the aging brain (stroke, language disorders, Mood Depressive Disorder (MDD), …). Though the concept of using neurofeedback paradigms for brain therapy has somehow been experimented recently (mostly through case studies), performing neurofeedback through simultaneous fMRI and EEG has almost never been done before so far (two teams in the world including us within the HEMISFER CominLabs project). This project will be conducted through a very complementary set of competences over the different involved teams: Empenn U1228, HYBRID and PANAMA Teams from Inria/Irisa Rennes and EA 4712 team from University of Rennes I.

PHRC EMISEP: Evaluation of early spinal cord injury and late physical disability in Relapsing Remitting Multiple Sclerosis: €200k for 2016-2019

Participants : Élise Bannier, Christian Barillot, Emmanuel Caruyer, Benoit Combès, Olivier Commowick, Gilles Edan, Jean-Christophe Ferré, Haykel Snoussi.

Multiple Sclerosis (MS) is the most frequent acquired neurological disease affecting young adults (1 over 1000 inhabitants in France) and leading to impairment. Early and well adapted treatment is essential for patients presenting aggressive forms of MS. This PHRC (Programme hospitalier de recherche clinique) project focuses on physical impairment and especially on the ability to walk. Several studies, whether epidemiologic or based on brain MRI, have shown that several factors are likely to announce aggressive development of the disease, such as age, number of focal lesions on baseline MRI, clinical activity. However, these factors only partially explain physical impairment progression, preventing their use at the individual level. Spinal cord is often affected in MS, as demonstrated in postmortem or imaging studies. Yet, early radiological depiction of spinal cord lesions is not always correlated with clinical symptoms. Preliminary data, on reduced number of patients, and only investigating the cervical spinal cord, have shown that diffuse spinal cord injury, observed via diffusion or magnetisation transfer imaging, would be correlated with physical impairment as evaluated by the (EDSS) Expanded Disability Status Scale score. Besides, the role of early spinal cord affection (first two years) in the evolution of physical impairment remains unknown.

In this project, we propose to address these different issues and perform a longitudinal study on Relapsing Remitting Multiple Sclerosis (RRMS) patients, recruited in the first year of the disease. Our goal is to show that diffuse and focal lesions detected spinal cord MRI in the first two years can be used to predict disease evolution and physical impairment at 5 years. Twelve centers are involved in the study to include 80 patients.

To date, all subjects have been included. Haykel Snoussi defended his PhD Thesis on diffusion imaging in the spinal cord starting with distortion correction.

B. Combès started as a post-doc in November 2016 to process the EMISEP imaging data, starting with morphological data processing (registration, segmentation) and magnetization transfer data processing.

MS-TRACTS (ARSEP and COREC funding): Estimating the impact of multiple sclerosis lesions in motor and proprioceptive tracts, from the brain to the thoracic spinal cord, on their functions, assessed from clinical tests and electrophysiological measurements: 45k€ (2019-2021).

Participants : Élise Bannier, Benoit Combès.

Previous studies, whether epidemiologic or based on brain MRI, have shown that several factors were likely to announce aggressive development of the disease, such as age, clinical relapses, number of focal lesions on baseline MRI. However, these factors only partially explain physical disability progression, preventing their use at the individual level. The access to advanced brain and cord MR images, the development of associated processing tools combined. We hypothesize that a fine assessment of damage on specific networks, from the brain to the thoracic cord, offers a relevant biomarker of disability progression in MS. Such damage assessments must take into account both lesion location, assessed on structural brain and cord MR images and lesion severity, assessed using quantitative MR images. We propose to test this hypothesis by combining assessments of lesion location and severity on corticospinal and proprioceptive tracts from the brain to the thoracic cord with clinical and electrophysiological measurements. This study includes two French centers (Rennes, Marseille) and includes a total of 60 patients. The expected outcome is to obtain early biomarkers of physical impairment evolution in RRMS patients, first treated with immunomodulatory treatment. The long-term goal is to provide the clinician with biomarkers able to anticipate therapeutic decisions and support the switch to alternative more aggressive treatment.

PIA projects

The HEMISFER Project: (€400k for 2017-2019)

Participants : Élise Bannier, Isabelle Bonan, Isabelle Corouge, Claire Cury, Jean-Christophe Ferré, Jean-Yves Gauvrit, Pierre Maurel, Christian Barillot.

The HEMISFER project ("Hybrid Eeg-MrI and Simultaneous neuro-FEedback for brain Rehabilitation") is conducted at Inria Rennes with the support of the Labex "CominLabs" (https://iww.inria.fr/cominlabs-newsletter/april-2013-four-projects-selected/#hemisfer). The goal of HEMISFER is to make full use of the neurofeedback paradigm in the context of rehabilitation and psychiatric disorders. The major breakthrough will come from the use of a coupling model associating functional and metabolic information from Magnetic Resonance Imaging (fMRI) to Electro-encephalography (EEG) to "enhance" the neurofeedback protocol. We combine advanced instrumental devices (Hybrid EEG and MRI platforms), with new man-machine interface paradigms (Brain computer interface and serious gaming) and new computational models (source separation, sparse representations and machine learning) to provide novel therapeutic and neuro-rehabilitation paradigms in some of the major neurological and psychiatric disorders of the developmental and the aging brain (stroke, attention-deficit disorder, language disorders, treatment-resistant mood disorders, etc.). This project involves with the HYBRID and PANAMA Teams from Inria Rennes, the EA 4712 team from University of Rennes I and the ATHENA team from Inria Sophia-Antipolis. This work benefits from the research 3T MRI and MRI-compatible EEG systems provided by the NeurInfo in-vivo neuroimaging platform on which these new research protocols aree set up. A budget of 500K€ is provided by CominLabs to support this project (through experimental designs, PhDs, post-docs and expert engineers).

France Life Imaging (FLI): 2012-2023, €2000k (phase 1) + €1200k (phase 2)

Participants : Christian Barillot, Olivier Commowick.

France Life Imaging (FLI) is a large-scale research infrastructure project to establish a coordinated and harmonized network of biomedical imaging in France. This project was selected by the call “Investissements d’Avenir - Infrastructure en Biologie et Santé”. One node of this project is the node Information Analysis and Management (IAM), a transversal node built by a consortium of teams that contribute to the construction of a network for data storage and information processing. Instead of building yet other dedicated facilities, the IAM node use already existing data storage and information processing facilities (LaTIM Brest; CREATIS Lyon; CIC-IT Nancy; Empenn U1228 Inria Rennes; CATI CEA Saclay; ICube Strasbourg) that increase their capacities for the FLI infrastructure. Inter-connections and access to services are achieved through a dedicated software platform that is developed based on the expertise gained through successful existing developments. The IAM node has several goals. It is building a versatile facility for data management that inter-connects the data production sites and data processing for which state-of-the-art solutions, hardware and software, are available to infrastructure users. Modular solutions are preferred to accommodate the large variety of modalities acquisitions, scientific problems, data size, and to be adapted for future challenges. Second, it offers the latest development that are made available to image processing research teams. The team Empenn fulfills multiple roles in this nation-wide project. Christian Barillot is the chair of the node IAM, Olivier Commowick is participating in the working group workflow and image processing and Michael Kain is the technical manager. Apart from the team members, software solutions like MedInria and Shanoir are part of the software platform.

OFSEP: €175k for 2017-2019

Participants : Élise Bannier, Christian Barillot, Olivier Commowick, Gilles Edan, Jean-Christophe Ferré, Francesca Galassi.

The French Observatory of Multiple Sclerosis (OFSEP) is one of ten projects selected in January 2011 in response to the call for proposal in the “Investissements d’Avenir - Cohorts 2010” program launched by the French Government. It allows support from the National Agency for Research (ANR) of approximately 10 million € for 10 years. It is coordinated by the Department of Neurology at the Neurological Hospital Pierre Wertheimer in Lyon (Professor Christian Confavreux), and it is supported by the EDMUS Foundation against multiple sclerosis, the University Claude Bernard Lyon 1 and the Hospices Civils de Lyon. OFSEP is based on a network of neurologists and radiologists distributed throughout the French territory and linked to 61 centers. OFSEP national cohort includes more than 50,000 people with Multiple Sclerosis, approximately half of the patients residing in France. The generalization of longitudinal monitoring and systematic association of clinical data and neuroimaging data is one of the objectives of OFSEP in order to improve the quality, efficiency and safety of care and promote clinical, basic and translational research in MS. For the concern of data management, the Shanoir platform of Inria has been retained to manage the imaging data of the National OFSEP cohort in multiple sclerosis.