SEP (Sclérose en Plaques)

COORDINATEUR SCIENTIFIQUE: Francois COTTON, PUPH, Chef de Service de Radiologie au HCL, Groupement Hopsitalier Lyon-Sud.

Membres du Projet: Equipe 5:  Dominique Sapey-Marinier. Equipe 2: C. Frindel, D. Rousseau. 

I. Contexte socio-économique:

La sclérose en plaques (SEP) est une maladie chronique , inflammatoire et démyélinisante, touchant à la fois les tissus de la substance blanche (SB) et de la substance grise (SG) cérébrale et médullaire. Bien que les lésions de SB soient facilement visualisées par IRM conventionnelle, la détection d'altérations dans la SB d’apparence normale (SBAN) et dans la SG reste difficile. A cet effet, de nouvelles techniques d’acquisition IRM et de post-traitement sont développés pour mieux caractériser ces mécanismes pathologiques. Les IRM pondérées en T1, T2 et T2 * et FLAIR sont utilisées pour mesurer la charge lésionnelle et l’atrophie cérébrale par segmentation des tissus des lésions, et des compartiments cérébraux (LCS, SG et SB). En outre, des techniques plus avancées telles que l’imagerie spectroscopique (ISRM) et l’IRM de tenseur de diffusion (DTI) permettent de mieux caractériser respectivement les altérations métaboliques diffuses et micro-structurales dans les lésions, les tissus de SBAN et les structures sous-corticales de SG (Thalamus, noyaux caudés).

II. Lien avec les Equipements et Investissements d'avenir: Equipex LILI (plateforme PET-MR plateforme), LabEX Primes.

III. Objectifs du projet:  L'objectif du groupe SEP est de mieux caractériser les modifications engendrées par la SEP dans plusieurs structures (noyaux gris, cervelet , ... ) et différents tissus (SB, SG) chez des patients porteurs de différentes formes cliniques de la maladie telles que la forme rémittente-récurrente (RR ), progressive secondaire (SP) et progressive d’emblée ou primaire (PP). Les corrélations entre ces différents marqueurs (charge lésionnelle, morphométrique, métabolique et diffusivité) sont ensuite analysées entre eux et avec l'état clinique des patients, et de manière longitudinale, afin de mieux comprendre l'évolution de chaque forme clinique.

IV. Les moyens du projets:

Financement obtenus: 

Projets nationaux

  • Partner in transverse program of CREATIS including : ANR National Infrastructure FLI – France Life Imaging (Partner)
  • ANR Equipex LILI– Lyon Integrated Life Imaging (Partner)
  • ANR Labex PRIMES – Physique, Radiobiologie, Imagerie Médicale et Simulation (WP2)
  • ANR-10-COHO-002, Imagerie (S. Hannoun, F. Durand-Dubief, D. Sappey-Marinier, F. Cotton) Programme des Investissements d’Avenir Cohorte nationale OFSEP – 2010_2020, (PI: Christian Confavreux, Sandra Vukusic)

Projets européens

  • FP6/FAST – 2006-2011, 13 partners (10 academic, 3 industrial), PI: Danielle Graveron-Demilly (CREATIS, Lyon)
  • FP7/TRANSACT - 2013-2017, 13 partners (10 academic, 3 industries) PI: Sabine Van Huffel (Leuven), (National PI: Dominique Sappey-Marinier).

Partenaires industriels: Guerbet (Contrast agents evaluation in the brain), SANOFI (New neuroprotective treatment evaluation)

Organisation de conférences et congrès

  • 12ème Congrès du GRAMM (Lyon, 2008) and 13ème Congrès du GRAMM (Rennes, 2011)
  • Workshop of French Imaging Platform FLI (Lyon, 2012), Journée « Etat de l’art en imagerie » JFR-FLI (Lyon , 2013)
  • Journée SFRMBM aux Congrès des Journées de Radiologie Françaises (JFR) (Paris, 2009-2014)
  • Journée SFRMBM au 30ème Congrès de l’ESMRMB (Toulouse, 2013).

Dernier Worshop interne: le ?? . Programme et présentations powerpoints accessibles aux membres actifs du Projet sur l'intranet de CREATIS au lien suivant: En savoir plus...

V. Les Publications 2016 du Projet SEP:

(A REMPLIR et METTRE A JOUR )

1. MR Spectroscopy characterization of Multiple sclerosis patients : M. Bagory, F. Durand-Dubief, D. Ibarrola, J-C. Comte, F. Cotton, C. Confavreux and D. Sappey-Marinier: Implementation of an absolute brain 1H-MRS quantification method to assess different tissue alterations in multiple sclerosis. IEEE Trans Biomed Eng. 2012 Oct;59(10):2687-94.

2. Evaluation of Coils for Imaging Histological Slides: Signal-to-Noise Ratio and Filling Factor Dung Minh Hoang, Evelyn B. Voura, Chao Zhang, Latifa Fakri-Bouchet, and Youssef Zaim Wadghiri, Magn Reson Med. 2013 Jul 15.

VI. les Collaborations

  • Belgium: Sabine Van Huffel, Leuven University, Leuven MR Spectroscopy processing and classification methods
  • Canada: Douglas L. Arnold, Mc Gill University, Montreal, Quebec
  • Danemark: Leif Oestergaard , Aarhus University, Aarhus MRI prediction of stroke outcome Danemark Thomas Vorup-Jensen, Interdisciplinary Nanoscience Center, Aarhus Molecular imaging of neuro-inflammation: molecular targeting Germany Götz Thomalla, UKE, Hamburg MRI prediction of stroke outcome
  • United-States: Charles R.G. Guttmann, Boston MRI characterization in Multiple Sclerosis
  • France: Michel Lagarde, Laboratoire de Recherche en Cardiovasculaire, Métabolisme, Diabétologie et Nutrition (CarMeN, U1060 Inserm), Lyon Novel engineered polyunsaturated acid as a treatment of cerebral ischemia
  • France: Serge Nataf, Centre de Recherche en Neurosciences de Lyon (CRNL, UMR CNRS 5292, UMR_S 1028 Inserm), Lyon Molecular imaging of neuro-inflammation: cell imaging and therapy
  • France: Christiane Charriaut-Marlangue, Physiopathologie, conséquences fonctionnelles et neuroprotection des atteintes au cerveau en développement (U676 Inserm), Paris Post-conditioning as a treatment of cerebral ischemia
  • France: Stéphane Parola, Laboratoire de Chimie de l’ENS Lyon (UMR CNRS 5182), Lyon Molecular imaging of neuro-inflammation: contrast agents
  • France: Emmanuelle Canet-Soulas, Laboratoire de Recherche en Cardiovasculaire, Métabolisme, Diabétologie et Nutrition (CarMeN, U1060 Inserm), Lyon Molecular imaging of neuro-inflammation: non-human primate models
  • France: Patrick Poulichet, Laboratoire ESYCOM, ESIEE Paris Portable NMR system: Modeling, Design and optimization Tunisia Cherif Dridi, Monastir University of sciences NMR microsystems for biomedical applications
  • Vietnam: Pham Huy Hoang and Phan Dinh HUAN, Ho Chi Minh University of Technology Ho Chi Minh Polytechnic Institute Portable NMR system: Modeling, Design and optimization USA Youssef Zaim Wadghiri, NYU School of Medicine Center for Biomedical Imaging Development of Coils and Microcoils: NMR applications on animals models of Alzheimer

VII. Highligts 

Characterization of subcortical gray matter using DTI in MS • S. Hannoun, F. Durand-Dubief, C. Confavreux, D. Ibarrola, N. Streichenberger, F. Cotton, C. Guttmann, D. Sappey-Marinier: DT-MRI Evidence for Extra-Axonal Neuronal Degeneration in Caudate and Thalamic Nuclei of MS Patients. American Journal of Neuro-Radiology 2012 Aug;33(7):1363-8.

First, we have developed of an absolute 1H MR spectroscopy quantification method showing increases of choline, creatine, and myo-inositol concentrations in PP and SP patients compared to controls, whereas the concentration of N-acetyl compounds remained constant. These findings suggest choline concentrations and Cho/tNA ratio as putative markers of progressive onset to monitor neurodegenerative processes (Bagory et al., 2012).

Second, significant correlations were observed between metabolic contents and DTI metrics in WM. A comparison analysis of these methods demonstrated a better sensitivity/specificity of DTI over MRSI (Hannoun et al 2012). Nevertheless, NAA/Cho ratio could better differentiated PP patients from controls. If diffusivity changes related to microstructural alterations were correlated with metabolic changes, DTI provided a better sensitivity to detect early changes, particularly in RR patients, subject to inflammatory processes. In contrast, the better specificity of metabolic ratios to detect axonal damage and demyelination may provide a better index for identification of PP patients.

Third, the DTI analysis of subcortical GM nuclei showed a significant FA increase in the caudate and the thalamus of MS patients. This result was associated with volume decreases of both nuclei, suggesting that FA may constitute a sensitive marker of neurodegenerative processes, such as dendrites loss and/or swelling of neuronal cell bodies in GM. Figure 2: On left, colored FA maps showing increased FA values : 1) in thalamus compared to caudate in Control (A) and 2) in MS patient (B) compared to Control (A). On right, the increased FA is significantly correlated with the atrophy of the caudate nuclei in MS patients but not in Controls.

VIII. Perspectives

Concerning the MS program, these methodological developments, particularly in DTI, will be applied to better characterize the alterations along the WM fibers to better explain the retro/anterograde effects of lesions on different WM or GM tissue (corpus callosum, cerebellum…). For this purpose, DTI at high angular resolution will be developed at 3T. This research will continue in the frame of the national cohort program “OFSEP” (Observatoire National de la Sclérose en Plaques). With the recent (2011) venue of 2 permanent staff member experts in image processing in the team, new image processing approaches will be developed in synchronization with clinical and preclinical studies. This includes new inverse problem approach for the deconvolution problem of MR perfusion imaging, the quantification of nanoparticules in phase contrast X-ray imaging with detection-based phase retrieval in synchrotron imaging to go beyond the sole visualization of inflammatory. Also, as another illustration, we will undertake the quantification of the shape of lesions in stroke and MS and their relation to the evolution of the lesions. New instrumentation methods will be developed in collaboration with team 5 of CREATIS to perform continuous acquisition of cerebral blood flow together with ECG for patients monitoring after stroke.

REUNIONS:

Février 2017: 

CR de la réunion

Physiopathologie de la SEP