Présentation Denis Le Bihan/Prix Louis D
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Le Cerveau de Cristal Denis Le Bihan NeuroSpin, CEA-Saclay, France IMAGERIE PAR RESONANCE MAGNETIQUE L’eau: une source de signal pour de multiples contrastesWATER: 90% of molecules, 70% body weight EAU (noyau hydrogène) Radiologues: Magiciens manipulant l’aimantation de l’EAU (et sa relaxation)! IRM: image virtuelle de l’aimantation des molécules d’eau du cerveau D. Le Bihan Nov 2012 Le cerveau…. Une organisation par régions La révolution de l’image… filleCouplage de la physique entre localisation et de l’informatique et fonction (Broca, circa 1861) 1972-82: Scanner-X, puis IRM: Le cerveau normal dissection virtuelle du cerveau malade Un des secrets du cerveau réside dans son architecture: fonction et localisation sont intimementD. Le Bihan Nov 2012 liés, à toutes les échelles, d’où l’importance de la neuroimagerie… Development of the central nervous system At birth the brain weight is 350g (1400g at the end of teenagehood) ALL neurons (100 billions…) are in place, mainly F. Brunelle et al. Necker Hosp. at the brain surface (2-4 mm cortical ribbon): production of more than 250,000 neurons per minute during pregnancy. Connexions (synapses) develop during the last months of pregnancy, up to about 500 synapses/neuron (>10 000 in adults) 27 weeks 24 weeks Gray matter M. Dhenain, E. Russel et al. Caltech (Mangin, Cachia at al.) High 3D resolution -fine anatomy Mouse-individual embryo: 13.5 variations days after conception (11.7T MRI) No ionizing radiations: -imaging in babies, children 32 weeks Mouse brain: 1gram! White matter D. Le Bihan Nov 2012 100 millions neurons… Hypertrophy of hippocampus in London taxi drivers Gènes, Environnement & Plasticité Long term platicity Maguire et al., PNAS, 2000 The pianist’s brain Plasticity & learning: Jugglers Short term plasticity La Timone Hospital + SHFJ/CEA + McGill University (ICBM) Draganski et al., Nature, 2004 D. Le Bihan Nov 2012 La révolution de l’imagerie… voir le cerveau normal un travail IRM: Fonction Structure IRM fonctionnelle D. Le Bihan Nov 2012 ..."The brain possesses an intrinsic mechanism by which its vascular supply can be varied locally in correspondence with local Voir c’est croire… variations of functional activity"... Roy, C.W. & Sherrington, C.S. J Physiol 1890, 11: 85-108. VISION IRM fonctionnelle (fMRI) Eau (noyau hydrogène Anatomie Iron Couplage neurovasculaire: Augmentation débit sanguin dans Seiji Ogawa les régions activées Changement de l’aimantation oxyHb de l’eau près des capillaries Hemoglobin sanguins des régions activées D. Le Bihan Nov 2012 déoxyHb 1990- … Blood Oxygen Level Dependent fMRI Voir notre monde interne: Imagerie mentale Imagination Perception VISION -0.5 0 14 28 0 0.5 1 1.5 2 2.5 Klein I, Paradis AL, Poline JB, Kosslyn SM, Le Bihan D (2000). J. Cogn. Neurosci. Visual activation during Braille reading in congenital blind people (D.Sadato Le Bihan Nov et 2012 al. Nature, 1995) « Mind » reading… … consciousness brain-machine interfaces D. Le Bihan Nov 2012 1985: WATER DIFFUSION MRI (from birth to adolescence) Infering microstructure from macroscopic resolution Macroscopic scale (millimeters) Water 1,5Tesla magnet1985….1989… 1991… ..1992…1994….1998… (hydrogen nuclei) ...2004… ....2001….2006…Contrast: water (15000 Gauss) Stroke Brain connectivity Cancer Brain magnetizationfunctional MRI D <x2>1/2 Brownian motion of water ? 17 Apparent Diffusiond 50 A CoefficientRestricted MapPermeable Barriers B Hindered 50 Td1/2 Free water: D 3 10-9m²/s Microscopic scale <x²>1/2 = 2 D t ( 17mm/50ms) (micrometers) Einstein 1905 Molecular-kinetic theory of heat to demonstrate D. Le Bihan Nov 2012 the existence of atoms IRM de diffusion: anisotropie tissulaire Anisotropie de diffusion Baisse de la diffusion de l’eau fibres de matière blanche (Moseley 1990: cat brain & spine) DTI Z l1 Dxx Dxy Dxz Y l Dyx Dyy Dyz l3 2 X D= [ ] Dzx Dzy Dzz 1991: Myelin fiber orientation1992 mapping-94: concept Douek et al. JCAT, 1991 (fiberDiffusion direction Tensor color encoding Imaging) Key assumption: D. Le Bihan Nov 2012 MainC. Poupon, fiber direction J.F. Mangin aligned et al., along MICCAI, highest 1998 diffusivity axis IRM de diffusion: Du mouvement brownien au “Human Brain Connectome” A. Vilanova et al. Eindhoven University of Technology Hagmann P. et al. PloS Biol 2008 Mori S. et al. Johns Hopkins University The Human Brain Connectome (30M$) NIH project Van Wedeen et al. Science 2012 Guevara et al, 2011-12 Poupon et al. (Connectomist) D. Le Bihan Nov 2012 CONNECT/NEUROSPINPoupon et al. (Connectomist /NeuroSpin) IRM de diffusion: Développement cérébral, plasticité, dysconnexions 2-4 month babies Maturation of language networks 6 ILF, FOF 5 UF Pianist brains Bengtsson et al. Nat. NS. 2008 4 MLF 3 AF inf 2 AF mid, lateral ILF 1 AF sup, SLF Asymmetry of temporo-frontal connections (arcuate fasciculus) is already present between 1 and 3 months. Dubois, Dehaene-Lambertz et al., Cerebral Cortex2008 Lateralization Index FA in Arcuate fasciculus Klingberg T., et al. Neuron 2000 12 Dyslexia % 8 Left > 4 Right 0 Schizophrenia -4 Right > Skelly, et al. Schizo. Res. 2008 -8 Left -12 D. Le Bihan Nov 2012 parietal temporal Neuroimagerie: Multiéchelle! Hier & aujourd’hui: architecture fonctionnelle 1000 millimètres macroscopique: MACRO -Codes cognitifs Van Wedeen et al. Science 2012 -Connexions Aujourd’hui & demain: Gènes et cerveau 22000 gènes (1010 bits), 1011 neurones, 1015 synapses! Demain, le « code neural»: MESO Set de clusters cellulaires assurant des briques de fonctions élémentaires, mises en connexions pour élaborer des fonctions « supérieures », relation MICRO mésoscopique dynamique entre structure tissulaire et fonction La santé: 6 months 9 months Prévention, diagnostic précoce (ALZ, psychiatrie) Rééducation/reprogrammation2001 NeuroSpin Founding (AVC, traumatismes) Motto 0.000001 14 months 20 months Thérapies2009 Japan personnalisées RIKEN BSI Director vision millimètre D. Le Bihan Nov 2012 Mésoscale2013 & IRM Obama’s(~100mm )Brain: Structure Activity & MapFonction Project! Instruments are key to groundbreaking science… Large Instruments for science: High energy, particles physics Higgs boson (CERN, RIKEN,etc) CERN Astronomy and astrophysics Universe (Hubble telescope) Neuro-physics NeuroSpin… Aimed at ultra-high field MRI/MRS systems: 3T, 7T, 11.74T wide-bore for human studies Interdisciplinary effort 17.18T (rodents) under one roof D. Le Bihan Nov 2012 Human brain explorer NeuroSpin, a concept unique in the world Clinical care facility *: world first (8 hospital beds, private Whole-body 3T MRI examination rooms, MEG) Whole-body 7T 11.74/900mm* logistics To be announced Library & 17.2T/260mm* Conference Resolution: 80 micrometers (mouse) room Laboratories, electronics, mechanics, chemistry shops and offices Industry labs/offices Animal care facility (transgenic mice, primates, training rooms, surgical suit) Accelerate translational research D. Le Bihan Nov 2012 CEA/Irfu design for NeuroSpin 90cm bore 11.74Tmagnet They did not know it was impossible, so they made it… (Mark Twain) 4,6 m Vacuum chamber 77K screen Compensation Main coils 4,7 m 4,7 0.90m Whole-body actively shielded11.74T/500MHz magnet: - cryostat: 4.6x4.7x4.7m3, 900mm internal diameter , 150 tons - wetted double pancakes in superfluid He: 1.8K pressured He II - superconducting wire: 65t NbTi (182 km) 9.2x4.9mm² section, 1500 amp in driven-mode (ext power supply) Cryogenic satellite Hydraulic, vacuum and electrical links towards magnet cryostat are realised within multipleD. Le Bihan transferNov 2012 line (cryoline) Molecular Imaging Rat brain tumor model 19 F MRI of aνβ3 receptors with RGD- functionalized PFOB NP in U87 mice 19F PFOB based emulsion perfluorooctylbromide nanoparticles (PFOB) Alzheimer disease marker F F F F F F F F Br F F F F F F F F F Sensitivity threshold is ~100 pM Giraudeau C, Flament J, Marty B, Boumezbeur F, Mériaux S, Robic C, Port M, Tsapis N, Fattal E, Giacomini E, Lethimonnier F, Le Bihan D, Valette J. A new paradigm for high-sensitivity 19F magnetic resonance imaging of perfluorooctylbromide. Magn Reson Med. 2010 Apr;63(4):1119-24 D. Le Bihan Nov 2012 International integration – Europe (CONNECT, ISEULT, EATRIS, EuroBioimaging/FLI, etc.) – International teams/collaborations University of Freiburg, Germany Institute fur Medizin, Julich, Germany Max Planck Institute Tubingen, Germany University of Leuwen, Belgium Kyoto University, Japan Tokyo University, Japan NIH, Bethesda, USA University of Minnesota, USA Nat. Research Council, Canada Tel Aviv University, Israel Nat. Yang-Ming Univ. Taipei … Industrial partners/clients – MRI and contrast agents: Guerbet, Siemens, Bruker Regional integration – Pharmaceutical companies –Healthcare competitivity pole (cluster) of the Paris region (Medicen) –Orsay (Paris-South University), Paris-Saclay campus, NeuroSaclay campus –Federative Research Institute (IFR 49) with Paris Hospitals Connecting basic research centers to research hospitals, leading schools and university D. Le Bihan Nov 2012 D. Le Bihan Nov 2012 .