CERN, December 9th, 2016
From the Proton to the Human Brain
Denis Le Bihan NeuroSpin, CEA-Saclay, France The radiology revolution from dried bones… …. to wet tissues CT Roentgen Hounsfield
Roentgen First Physics Nobel Prize 1901
Nobel Prize in Medicine MRI and Physiology, 1979 X-rays and wet tissues: When physics married computer sciences “Röntgen photography” plaque published in 1896 "Nouvelle Iconographie de la Salpetriere",
D. Le Bihan Dec. 2016 Coupling between localization & function (Broca, circa 1861)
D. Le Bihan Dec. 2016 Coupling between localization & function (Broca, circa 1861) MRI: Magnetic avatar of brain water…. Virtual dissection of the brain Looking into the brain MAGNETIC RESONANCE IMAGING
D. Le Bihan Dec. 2016 The song of the water molecules Coupling between localization & function (Broca, circa 1861) MRI: Magnetic avatar of brain water…. Virtual dissection of the brain Looking into the brain MAGNETIC RESONANCE IMAGING
D. Le Bihan Dec. 2016 The song of the water molecules MAGNETIC RESONANCE IMAGING The song of the water molecules Hypertrophy of hippocampus in London taxi drivers
Long term platicity Maguire et al., La Timone Hospital SHFJ/CEA PNAS, 2000 McGill University (ICBM) Hippocampus: Inner brain « GPS »
D. Le Bihan Dec. 2016 MAGNETIC RESONANCE IMAGING The song of the water molecules Hypertrophy of hippocampus in London taxi drivers
Long term platicity Maguire et al., La Timone Hospital SHFJ/CEA PNAS, 2000 McGill University (ICBM) Hippocampus: Inner brain « GPS »
Hypotrophy of hippocampus in Alzheimer patients
D. Le Bihan Dec. 2016 MAGNETIC RESONANCE IMAGING The song of the water molecules Hypertrophy of hippocampus in London taxi drivers
Long term platicity Maguire et al., La Timone Hospital SHFJ/CEA PNAS, 2000 McGill University (ICBM) Hippocampus: Inner brain « GPS »
Hypotrophy of The pianist’s brainhippocampus in Alzheimer patients
Whitaker KJ PNAS 2016 Plasticity: The baby’s brain D.Genes Le Bihan Dec, . Environment2016 , Synaptic epigenesis MAGNETIC RESONANCE IMAGING The song of the water molecules Hypertrophy of hippocampus in London taxi drivers
Long term platicity Maguire et al., La Timone Hospital SHFJ/CEA PNAS, 2000 McGill University (ICBM) Hippocampus: Inner brain « GPS »
Hypotrophy of The pianist’s brainhippocampus in Alzheimer patients
Whitaker KJ PNAS 2016 Plasticity: The baby’s brain D.Genes Le Bihan Dec, . Environment2016 , Synaptic epigenesis The DANCE« Standard of the» MRI: water The molecules SONG :of WATER the water DIFFUSION molecules MRI Infering microstructure from macroscopic resolution? Macroscopic scale (virtual biopsy) (millimeters) MRI
SHFJ/CEA, Orsay circa 1984 Le Bihan & Breton, 1985 Contrast: « water » 2 1/2 D
A Restricted
Permeable 1/2 Barriers B 50 Td Hindered
SHFJ/CEA, Orsay circa 1984 Le Bihan & Breton, 1985 ACUTE STROKE Contrast: « water » 2 1/2 D
A Restricted
Permeable 1/2 Barriers B 50 Td Hindered
Z l1 Dxx Dxy Dxz Y l Dyx Dyy Dyz l3 2 X D= [ ] Dzx Dzy Dzz
Connectivity algorithms: Mori S et al. Ann. Neurol. 1999 Contouro TE et al., PNAS 1999 D.Poupon Le Bihan DecC. 2016 et al. MICCAI, 1998 DIFFUSION MRI: From Brownian motion to the Human Brain Connectome
Facebook network! A. Vilanova et al. Eindhoven University of Technology Hagmann P. et al. PloS Biol 2008 The Human Brain Connectome (30M$) NIH project
Guevara et al, 2011-12 Poupon et al.
D. Le Bihan Dec. 2016 CONNECT Consortium DIFFUSION MRI: From Brownian motion to the Human Brain Connectome Paris metro!
Facebook network! A. Vilanova et al. Eindhoven University of Technology Hagmann P. et al. PloS Biol 2008 The Human Brain Connectome (30M$) NIH project
Guevara et al, 2011-12 Poupon et al.
D. Le Bihan Dec. 2016 CONNECT ConsortiumPoupon et al. (Connectomist/NeuroSpin) DIFFUSION MRI: The Danse of Water Molecules Van Wedeen et al. Science 2012
2-4 month babies Brain development Maturation of language networks Mind disorders: Schizophrenia Skelly, et al. Schizo. Res. 2008
Asymmetry of temporo-frontal connections (arcuate fasciculus) is already present between 1 and 3 months Dubois J et al., Cerebral Cortex 2008
D. Le Bihan Dec. 2016 1985..1989..1991..1992..1994..1998..2004..2001..2006..2013..2016… Stroke Brain connectivity Cancer Brain fMRI Elastography
(Catani M, Oct. 2013) 20 years
D. Le Bihan Dec. 2016 The « image » revolution … seeing the normal brain at work
MRI: Structure Function
Brain architecture: Function and localization are intimely linked, at all
D. Le Bihan Dec. 2016 scales, hence the importance of neuroimaging. The « image » revolution … seeing the normal brain at work
Iron
Hemoglobin
déoxyHb MRI: Structure Function Neurovascular coupling: Increase of local cerebral blood flow in active regions Functional MRI Roy, C.W. & Sherrington, C.S. J Physiol 1890, 11: 85-108.
Seiji Ogawa Brain architecture: Function and localization are intimely linked, at all
D. Le Bihan Dec. 2016 scales, hence the importance of neuroimaging. Our inner word: Mental imagery
Imagination
Perception
VISION
D. Le Bihan Dec. 2016 Our inner word: Mental imagery
VISION
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0
0.5
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Klein I, Paradis AL, Poline JB, Kosslyn SM, Le Bihan D (2000). J. Cogn. Neurosci.
D. Le Bihan Dec. 2016 Our inner word: Mental imagery
VISION
Visual activation during Braille reading in congenital blind people D. Le Bihan Dec. 2016 (Sadato et al. Nature, 1995) Seeing is believeing!
WORDS
How many black dots?
D. Le Bihan Dec. 2016 Seeing is believeing!
Rubin’s figures: 2 (dark) faces…. or 1 (bright) vase…? Ambiguous figures and perceptual decision: Intrinsic fluctuations of mental states
D. Le Bihan Dec. 2016 Seeing is believeing!
WORDS
FFA: Fusiform face area
Rubin’s figures: 2 (dark) faces…. or 1 (bright) vase…? Ambiguous figures and perceptual decision: Intrinsic fluctuations of mental states
D. Le Bihan Dec. 2016 Hesselmann G, Kell C.A., Eger E., Kleinschmidt PNAS 2008 Nature, 2008 Motor cortex (final action)
Frontopolar cortex (unconscious decision)
Precuneus & cingular posterior cortex (decision is maintained in memory)
D. Le Bihan Dec. 2016 « Mind » reading… … consciousness brain-machine interfaces
D. Le Bihan Dec. 2016 Neuroimaging:A multiscale approach Yesterday & today: macroscopic functional 1000 architecture of the brain: millimeters Brodmann, 1908 MACRO -Functional MRI:Cognitive codes -Diffusion MRI:Connections
Today & tomorrow: Genes and brain, environment 20-25 103 genes (1010 bits), but 1011 neurons & 1015 synapses
Tomorrow, the « neural code»?
MESO Mesoscopic structure-function relationship: Limited set of low-level cell clusters («brainons ») underlying elementary functions connected in time MICRO and space to create high order functions 180 areas - Glasser et al. (HCP) « Health » aims: Nature 2016 Early detection of diseases (ALZ, psychiatry) Rehabilitation/reprogramming (« stroke », injuries) 0.000001 millimeter D. Le Bihan Dec. 2016 Mesoscale & MRI(~100mm): Structure & Function Instruments are key to groundbreaking science: Pushing the limits of MRI Large Instruments concept High energy, particles physics CERN, RIKEN, etc. CERN Astronomy and astrophysics Instruments Hubble telescope, Huygens-CassiniLeeuwenhoek’s probe Galilée’s lunette microscope Interdisciplinary effort under one roof Neuro-physics NeuroSpin (20012007) 2016 Aimed at ultra-high field MRI systems: Clinical 7T: 50 systems 1 preclinical magnet 17.6T (mouse) vertical (Wurzburg)
ATLAS Toroid magnet LHC quadrupole magnet
Bosons Proton/photon Deuterium/Tritium ITER TokamakCMS solenoid magnet
D.From Le Bihan DecHigh. 2016 Energy & Particle physics …. to Nuclear Fusion CEA/Irfu design for NeuroSpin 90cm bore 11.74Tmagnet (Th. Schild, Project Manager)
Whole-body actively shielded11.74T/500MHz magnet: - cryostat: 5x5.2m², 900mm internal diameter +++ - wetted double pancakes in superfluid He: 1.8K pressured He II bath connected to a cryoplant - superconducting wire: 69t NbTi (182 km), 9.2x4.9mm² section - nominal current: 1483 amp in driven-mode (ext power supply) - stored energy: 328 MJ, inductance 308H, 28A/mm² - overall weight: 132 tons, 170MPa hoop stress on conductor - actively shielded (5G line at 13m in axial direction, 10m radially) Luvata (USA) - Field homogeneity: 0.5ppm over 22cmDSV
D. Le Bihan Dec. 2016 - Field stability: <0.05ppm/h Novel geometry for MRI magnets: Double Pancakes (French magnet!)
Double pancake winding machine: Mandrel Radial pressing wheel Axial pressing conical rollers
Internal mandrel (not represented) Dedicated manufacturing processes were made
D. Le Bihan Dec. 2016 to build and assemble the pancakes (CEA/Alstom-GE) Active shielding coils Active shielding coils: - External diameter: ~4,3 m - Wire length: 24.7 km - Conductor layers: 36 - Conductor mass/coil: ~8t
E. Zanon spa., Italy,
Nominal + quench total stress remains under control : 82,5+111=193,5MPa He tank structure: several coils (<270MPa) inside one common bath (1.25 bars @1.8K) Wetted double pancakes in superfluid He to enhance cryostability: (1.8K D.pressured Le Bihan Dec. 2016 He II bath connected to a cryoplant General cryogenic layout for NeuroSpin 11.7T MRI system
Quench protection: High stored energy (340MJ), cryostable magnet quench protection by external dump resistor. (Quench voltage to ground 2000 V)
Cryogenic satellite (cryogenic, electrical and safety elements).
Hydraulic, vacuum and electrical links towards magnet cryostat are realised within a “caloduc”, multiple transfer line (cryoline)
Prototypes were built to test cryogenic concepts, model quench, check pressure D. Le Bihanbuilding, Dec. 2016 mechanical strength. Magnet in persistent mode (external power supply)
Power supply: Complexity and risk of failure of a large PS +stability number of high current superconducting joints/switches not in persistent mode but permanently connected to R a highly stable DC power supply PS (driven mode) prot augmented with a stability circuit (current limitator). Cryostat S2 I +δI I +δI I0+δI0 f coil coil f + S Lcoil Cold area Power
supply Rf Rcoil S1
D. Le BihanConcept Dec. 2016 (field stability, impact on magnet) was tested using ad-hoc prototypes. 4:High availability (24/24, 7/7, including French holidays & strikes)
Highly complex system (cryogenic plant with 1.8K pump, stabilized power supply, quench control, etc.) which requires highly automated controllers
D. Le Bihan Dec. 2016 They did not know it was impossible, so they made it. Mark Twain
11.7T Human MRI magnet
Human Brain Explorer Quest for the « brainon »…
D. Le Bihan Dec. 2016 Iseult/Inumac: A French-German industrial partnership to develop High Field Molecular Imaging financed partly by the partners and partly by the French Industrial Innovation Agency (Oséo) and the German BMBF.
Guerbet
CEA Univ (NeuroSpin, Irfu) of Freiburg
Siemens MS
Bruker Biospin MRI SYSTEM INTEGRATION: MRI GmbH .Develop MRI system at unprecedented performance (11.7T/900mm) for humans (magnet, cryostat)(Irfu) .New rf pulses & monitoring, coil design (CEA, Siemens, U. Tokyo, National Research Council Canada, NeuroSpin/Irfu), .Biological effect of electromagnetic fields, safety (U. Tokyo, J-NIOSH, DSV/FAR)
Molecular imaging
D. Le Bihan Dec. 2016 Iseult/Inumac: A French-German industrial partnership to develop High Field Molecular Imaging financed partly by the partners and partly by the French Industrial Innovation Agency (Oséo) and the German BMBF.
Guerbet
CEA Univ (NeuroSpin, Irfu) of Freiburg Numerical calculation of global and local SAR
Siemens MS
Bruker Biospin MRI SYSTEM INTEGRATION: RF design MRI GmbH Global SAR experimental validation .Develop MRI system at unprecedented performance (11.7T/900mm) for humans (magnet, cryostat)(Irfu) .New rf pulses & monitoring, coil design (CEA, Siemens, Gx U. Tokyo, National Research Council Canada, NeuroSpin/Irfu), Gy .Biological effect of electromagnetic fields, safety Gz (U. Tokyo, J-NIOSH, DSV/FAR) kT-point trajectory in spatial-frequency pace
3T Molecular7T imagingRF Shim7T kT-points 7T Local temperature increase after 30min RF exposure M. Cloos, N. Boulant, M. Luong, G. Ferrand, E. Giacomini, M.-F. D. Le Bihan Dec(CP. 2016 transmission) [Massire et al. 2012]. Hang, D. Le Bihan, and A. Amadon, NeuroImage 62:2140-50 (2012). NEUROSPINWHEN ART MEETS SCIENCE: NEUROSPIN ARCHES ? FuSuMaTechInitiative
SocialMRI 3T MRI Claude Vasconi, Architect 1940-2009 Empty arch
7T MRI Preclinical 7T MRI 11.7T MRI 17T MRI 11.7T MRI
D. Le BihanWho Dec. 2016 yearns for the impossible I love. Goethe Challenge for XXIth century: Clusters of 1000 neurons The Neural Code
Meso and microscopic scale (10-100 mm, 10-100 ms), multimodality huge datasets to acquire, transmit, process, archive Large assembly physics and mathematical models simulation New (intrinsic/extrinsic) contrast mechanisms, tracers molecular, biophysical interactions New MRI instrumentation, methods engineering simulation tools Brain individual variability, gene/environment interactions: disease diagnostic/prediction big data & data mining UHF mesoscale MRI
3T 7T Clinical 11.7T Preclinical
17.2T
Vol D. LeNeuroSpin Bihan Dec. 2016 11.7T Princeton University Press
A large infrastructure for brain imaging with UHF MRI
Brain science has no border: physicists, chemists, Total: 58Teslas! biologists, computer scientists, radiologists, neuroscientists, psychiatrists, statisticians, etc. International research institute (~25% international staff) -Europe (ERC/H2020, CONNECT, ISEULT, EATRIS, EuroBioimaging/FLI, HBP)
D. Le Bihan-International Dec. 2016 teams/collaborations (EU, Israël, US, Japan, China, Taiwan, etc.) Acknowledgements
IRFU MAGNET TEAM ALLARD Jérôme, ABDEL MAKSOUD Walid, ANSTETT Denys, ARRANGER Denis, AUBERT GUY, AUTHELET Gilles, BACHET Damien, BEAUVAIS Philippe, BAILLY Quentin, BAKAOU Ali, BARGUEDEN Patrick, BARRIERE Jean-Christophe, BAUDOUY Bertrand, BAZE Jean-Marc, BELORGEY Jean, BELTRAMELLI Joël, BERMOND STEPHANE, BERRIAUD Christophe, BOUDOUIN Romain, BOUSSUGE Thierry, BOUTY André, BOUZIAT Denis, BREDY Philippe, BRASSEUR Alain, BROUSSARD Sylvain, BURIDANT Grégory, Georges CHARPAK CAZANOUX Marc, CAZAUX Sandrine, CHANCE Antoine, CHARRIER Jean-Paul, CHESNY Philippe, CONTREPOIS Pascal, COULLOUX Gilles, CURTONI Aline, COROT Eric, DALLA FOGLIA THOMAS, DE 1924-2010 ANTONI Philippe, DE SOUSA Michel, DECHAMBRE Thierry, DESAILLY-GUYARD Catherine, DISPAU Gilles, DONATI André, DOUARIN Jean, DUBOUE BRUNO, DROUEN YANNICK, DUBOIS Olivier, ESTEVES Mario, ELEFANT Félix, FAZILLEAU Philippe, FAICT-BASTIN Sandrine, FONTAINE Philippe, GALLOYER Jean Maurice, GENINI Laurent, GHELLER Jean-Marc, GIBIER Dominique, GOC Jean- Jacques, GODON Pascal, GOURNAY Jean-François, GRAFFIN Patrick, GROS Pascal, GROUAS Nathalie, GUIHO Patrice, GUILLARD Jean- Christophe, HANUS Xavier, HENNION Vincent, HERVIEU Bertrand, JOANNEM Tom, JOUBERT Jean-Michel, JUSTER François, KUSTER Olivier, LANNOU Hervé, LE DORTZ Patrick, LE POUHALEC Philippe, LE NOA YANNICK, LEBOEUF René, LECOURT Laurence, LEVEQUE Pascal, LOISEAU Denis, LOTODE Ange, LOUCANO Delfim, LOUCHART Olivier, LYS Guillaume, MAGNIER Patrick, MANIL Pierre, MAILLERET Charles, MARIETTE Yannick, MASSINGER Mickaël, MATTEI Pierre, MAYRI Christophe, MEDIONI Damien, MEURIS Chantal, MOHAMED Azath, MOLINIE Frédéric, MOULIN Thierry, NEVES DA COSTA Joachim, NEYRIAL Hubert, NOURY Julien, NUNIO François, OUPLOMB Pierre, PAGET Florian, PAYN Alain, PERRIN Jean-Luc, PERON Cédric, PICCIRELLI Bénédicte, PONSOT Patrick, POTTIER Francis, POULIZAC Aubrey, PRZYBYLSKI Alain, QUETTIER Lionel, QUEINEC Yannick, RELLAND Johan, REY Jean-Michel, RONDEAUX Françoise, ROGER Arnaud, SAUCE Yannick, SAUDEMONT Jean-Claude, SCHILD Thierry, SCOLA Loris, SINANNA Armand, RUAT Maxime, GAO YUAN, LEBOEUF Vincent, PRZYBILSKI Henry, SOROKINA YULIA, STEPANOV VADIM, SUEUR Michel, SUBE Samuel, TELLIER Olivier, THINEL Jean, TOUSSAINT Jean Christian, TOUZERY Robert, VEDRINE Pierre, VIEIRA GOMES Adelino, VIEILLARD Laurence, WALTER Christian, ZAITSEV Iouri
NEUROSPIN 11.7T MRI TEAM ALLIROL Lionel, AMADON Alexis, BOULANT Nicolas, BOUMEZBEUR Fawzi, CHAZEL Edouard, CIUCIU Philippe, COTTON Joël, COSTE Arthur, DEVERRE Jean-Robert, HANG Marie-France, LE BIHAN Denis, LERMAN Cécile, LUONG Michel, POUPON Cyril, VIGNAUD Alexandre
D. Le Bihan Dec. 2016