ANR

ANR "TRANSLATE-MS-REPAIR", RPIB 2012 program

Participants : Laurence Catanese, Olivier Commowick, Isabelle Corouge, Jean-Christophe Ferré, Elise Bannier, Gilles Edan, Christian Barillot.

It is now commonly admitted that MS is not only an inflammatory disease but a neurodegenerative disease as well. This project is devoted to show that the olesoxime molecule is not only neuroprotective, but it has the ability to promote the maturation of oligodendrocyte progenitor cells (OPCs) into myelinating oligodendrocytes. However, before considering a large-scale clinical trial to assess efficacy. An important aspect is that to date, no treatment for neuroprotection / remyelination has reached the stage of clinical proof of concept that aims Trophos company who is leading this project. It appears that the best criteria for assessing neuroprotective/remyelinating effect of the drug candidate, are MRI criteria. However, these imaging criteria have not yet been validated for use in multicentre trials - so we will also check the feasibility of such measures under this condition. In addition to Trophos company, the partners of this project are AP-HM/CNRSCEMEREM-CRMBM, CHU Rennes, CHU Reims, and Inria-VISAGES.

ANR "MAIA", 2015 generic projects program

Participants : Maia Proisy, Pierre Maurel, Olivier Commowick, 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 technics 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 aims at 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 will be the design of such software tools for medical image / signal analysis, actually operational in clinical routine, and freely available. Academic researchers and industrial partners will work in close collaboration to reach that ambitious goal.

Competitivity Clusters

The HEMISFER Project

Participants : Elise Bannier, Isabelle Bonan, Isabelle Corouge, Jean-Christophe Ferré, Jean-Yves Gauvrit, Pierre Maurel, Lorraine Perronnet, Christian Barillot.

France Life Imaging (FLI)

Participants : Christian Barillot, Olivier Commowick, Florent Leray, Michael Kain, Yao Yao.

France Life Imaging (FLI) is a proposed large-scale research infrastructure project aimed at establishing a coordinated and harmonized network of biomedical imaging in France. This project was recently 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 build by a consortium of teams that will contribute to the construction of a network for data storage and information processing. Instead of building yet other dedicated facilities, the IAM node will use already existing data storage and information processing facilities (LaTIM Brest; CREATIS Lyon; CIC-IT Nancy; Visages U746 Inria Rennes; CATI CEA Saclay; LSIIT/ICube Strasbourg) that will increase their capacities for the FLI infrastructure. Inter-connections and access to services will be achieved through a dedicated software platform that will be developed based on the expertise gained through successful existing developments. The IAM node has several goals. It aims first at building a versatile facility for data management that will inter-connect the data production sites and data processing for which state-of-the-art solutions, hardware and software, will be available to infrastructure users. Modular solutions are preferred to accommodate the large variety of modalities acquisitions, scientific problems, data size, and adapted for future challenges. Second, it aims at offering the latest development that will be made available to image processing research teams. The team VISAGES 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 the technical manager. Apart from the team members, software solutions like medInria and Shanoir will be part of the final software platform.

OFSEP

Participants : Justine Guillaumont, Elise Bannier, Christian Barillot, Olivier Commowick, Gilles Edan, Isabelle Corouge, Jean-Christophe Ferré, Michael Kain, Inès Fakhfakh.

The French Observatory of Multiple Sclerosis (OFSEP) is one of 10 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.

Collaboration with the CEA (Commissariat à l'Energie Atomique): Standardization of Arterial Spin Labeling acquisitions and imaging data quality assessment in the context of dementia related studies

Participants : Elise Bannier, Christian Barillot, Isabelle Corouge, Jean-Christophe Ferré, Cédric Meurée.

duration: from August 2014 to December 2015

Around 900,000 people are affected by various forms of dementia in France. As an early and reliable diagnosis remains difficult to provide, neuroimaging is crucial as a diagnosis assistance by analyzing structural and functional brain abnormalities related to these diseases. The CATI (Centre pour l'Acquisition et le Traitement des Images) is a multicenter neuroimaging network dedicated to the management of dementia related imaging protocols. As VisAGeS and the Neurinfo platform are recognized for their expertise in Arterial Spin Labeling (ASL) acquisition and post-processing, a collaboration contract was signed between Inria and CEA, the coordinator of the CATI initiative, in order to host an engineer in the VisAGeS team for one year. The collaboration resulted in the standardization of the ASL acquisition parameters of the CATI protocols, the setup of these parameters on the scanneres participating in the CATI studies, as well as the development and the integration of post-processing and quality assessment tools into qualiCATI, the quality control software of the CATI.

PEPS JCJC CNRS INS2I: FastMicroDiff: Fast acquisition for microstructure-enabled diffusion MRI

Participants : Elise Bannier, Emmanuel Caruyer.

duration: from January 2015 to December 2015 Diffusion MRI is a unique tool for the observation of brain white matter structure in vivo. Several studies have shown that it is possible to estimate intrinsic tissue parameters from diffusion, such as axonal diameter, axonal density, orientation dispersion, compartment-specific diffusion coefficients, etc. However, the reconstruction of these parameters requires specific acquisition protocols, which are to date very long and therefore poorly compatible with in vivo applications. Besides, recent development have shown that a higher sensitivity to some microstructural paramters could be obtained using non-conventional diffusion gradient sequences, such as oscillating gradient waveforms. This project aims at developping faster acquisition methods, using sparse representation for microstructure-enabled diffusion signal and time-varying diffusion sensitizing gradients.

In cooperation with the Neurinfo imaging platform and Siemens, a modification of the protocol to enable the use of non-rectangular gradient pulses has been developped and is being tested on phantom. A group of 6 healthy subjects will be scanned using this novel protocol, and acquisition will be repeated 3 times for each subject so that we can evaluate the reproducibility of the technique.

PHRC EMISEP: Evaluation of early spinal cord injury and late physical disability in Relapsing Remitting Multiple Sclerosis

Participants : Elise Bannier, Christian Barillot, Emmanuel Caruyer, Olivier Commowick, Gilles Edan, Jean-Christophe Ferré, Anne Kerbrat.

duration: from January 2014 to December 2017 Multiple Sclerosis (MS) is the most frequent acquired neurological disease affecting young adults (1/1000 inhabitants in France) and leading to impairment. Early and well adapted treatment is essential in patients presenting aggressive forms of MS. This PHRC project focuses on physical impairment and especially on the ability to walk. Several studies, whether epidemiolgic or based on brain MRI, have shown that several factors were likely to announce aggressive development of the disease, such as age, number of focal lesions on baseline MRI, clinical activity. However, this 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 a 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 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 to perfom 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 on the spinal cord MRI in the first 2 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, 40 of the 80 subjects have been included. A PhD student started in November 2015 to work on diffusion imaging in the spinal cord.