Prsentation Denis Le BihanPrix Louis D'

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Water Diffusion MRI from birth to teenage hood
Denis Le Bihan NeuroSpin, CEA-Saclay, France
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WATER DIFFUSION MRI
 PLAIN  (STRUCTURAL) MRI circa 1985
MRI
Water (hydrogen nuclei)
1,5Tesla magnet (15000 Gauss)
Contrast water magnetization and
relaxation(tissue structure)
Macroscopic scale(millimeters)
?
Free water D ?3 10-9m²/s ltx²gt1/2 ? 17mm
(Td 50ms)
Microscopic scale (micrometers)
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Radiology 1986
? Diffusion Perfusion MRI
Confusion
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IntraVoxel Incoherent Motion (IVIM) imaging
(1986-88.. 2008)Radiology, 1988
Intercept ? f (perfusion fraction ? CBV
Slope gt true diffusion coefficient
Slope ? true diffusion coefficient
Pseudo-diffusionD l v /6
But wait for 2006Diffusion fMRI!
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Major application Diffusion MRI in acute stroke
(Michael Moseley, first in MCAO cat model, 1990)
Energy metabolism failure ? Cytotoxic edema
-Cell swelling increased tissue tortuosity
? -Decreased membrane exchange ? -Decrease
intracellular motion ?
30 to 50 diffusion coefficient drop in the
first 6 hours when an active treatment
(reperfusion) may still work
?
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Diffusion-sensitized MRI tissue microstructure
Cell swelling ? Decreased water diffusion

• Change in water diffusion coefficient with
  osmolality
• High osmolality ? cell shrinking, increased
  diffusion
• Low osmolality ? cell swelling, decreased
  diffusion
• Decreases water diffusion/cell swelling have been
  reported in - Stroke - Extra-physiological
  activation status epilepticus induced by
  bicuculline and cortical electroshocks (Zhong),
  spreading depression (Sotak, Moseley)

? mechanism???
Diffusion anisotropy ? Decreased water diffusion
? white matter fibers (Moseley 1990 cat brain
spine)
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Radiology 1990
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From Brownian motion to the Human Brain
Connectome
1991 Myelin fiber orientation mapping concept
1992-94 Diffusion Tensor Imaging
Non Gaussianhigh angular resolution models
Key assumption Main fiber direction aligned
along highest diffusivity axis
? 30MHuman Connectome Project (HCP/NIH)!
BrainVISA software Cointepas et al.
http//brainvisa.info
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Diffusion-sensitized fMRI _at_ 3T
Diffusion fMRI
BOLD fMRI
? No post-stimulus undershoot
? Early response (ltvascular events)? New (non
vascular) mechanism
Le Bihan et al. PNAS 103, 8263-8268, 2006
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Diffusion-sensitized MRI tissue events
1 - Cell swelling ? Decreased water diffusion

• Change in water diffusion coefficient with
  osmolality
• High osmolality ? cell shrinking, increased
  diffusion
• Low osmolality ? cell swelling, decreased
  diffusion
• Decreases water diffusion have been reported in
  - Stroke - Extra-physiological activation
  status epilepticus induced by bicuculline and
  cortical electroshocks (Zhong), spreading
  depression (Sotak, Moseley)

2 - Physiological neuronal activation ? cell
swelling
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Water diffusion model in the brain Back to
Einstein
Free diffusion Gaussian distribution of
displacements
For MRI Sexp (-b D)
human brain cortex
ltx²gt 2 Dt
Clark CA Le Bihan D, MRM, 2002
ln (S) ? b D
Biexponential behavior diffusion is not free ?
2 water pools?
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Visual cortex
2 KINDS OF WATER IN CELLS SLOW FAST DIFFUSION
POOLS

• Water diffusion in brain is mainly hindered by
  cell membranes
• Diffusion behavior is well described by a
  biexponential model
• Slow and fast diffusion pools do not coincide
  with the intra- and extracellular volumes
• but variations in slow/fast diffusion fractions
  correlate well with those of the EC/IC volumes
  (cell size)(stroke, osmotic challenges, status
  epilepticus, spreading depression)

• Water-membrane interface Long-range
  electrostatic trapping
• Protein  trapping  effects structured water
• Extend to adherent water layers out to 180nm (Xu
  Yeung, Science 1998, Vogler, 1998)
• ? 30 of cell water (Pissis, 1987)

ln (S) ? b D

• Slow diffusion pool structured water bound
  to membranes
• ADC changes with membrane surface interaction
  (cell size, anisotropy, cellularity,)

-
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 Life-scientists have ignored the water as the
fish forgets the water in the ocean Pollack
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• Upon activation about 0.5 of the cortex water
  shifts from a fast to a slow diffusion pool,
  which corresponds to a 1.7 swelling of the slow
  diffusion pool.

Bi-phasic water diffusion model prediction
Cells must swell
S So fslowexp(-b Dslow)ffastexp(-b Dfast)
exp (-TE/T2tissue)
Visual cortex
dffast - 0.52 0.23 dfslow 0.49 0.06
Slow diffusion pool water molecules bound to
membranes
Activation response, dS/S, increases with
diffusion-sensitization (b-value)
Fifast, slow exp(-bDi) / fslow exp(-bDslow)
ffast exp(-bDfast)
Cell activation ?? Increase water ordering ??
Cell membrane expansion
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Water the moleculeof the mind ?
Le Bihan D. The wet mind Phys. Med. Biol.
52557-90, 2007
BOLD fMRI
H2015 PET

• Active role of water in cell depolarization,
  action potential?-more water influx in cells
  than expected from ion transferts
• Role of blood water in heat transfert (increase
  in CBF)?-activation --gt heat release-increase
  of CBF and metabolism (energy demand) more to
  restore baseline conditions after activation,
  housekeeping
• Role of cell structure changes (swelling) in
  information flow-neurons glial cells as
  (reversible) piezo-electric transducers-faster
  than neurotransmission for local, intracotical
  networks

Rest
Activation
?blood flow?quantity of radioactive water in
activated tissues
?blood flow oxygenation?magnetized water
relaxation in/near vessels
Radioactive water
Magnetized water
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LRMNF LethimonnierC WigginsL CiobanuA
AmadonN BoulantF BouzmebeurJ ValetteS
MériauxF PouponE GiacominiL Laribière LNAOJF
ManginC PouponD RivièreY CointepasJB
PolineP CiuciuA Roche LBIM DhenainC WuB
Jerraya LBIOML Hertz-Pannier, L
AllirolInfirmièresManipulateurs
LCOGNS DehaeneG DehaeneC PallierA
Kleinschmidt Irfu/DSMP VédrinePh
RebourgeardJ BelorgeyC BériaudPh BrédyFP
FusterA HervéM LuongC MeurisF NunoA
SinannaL ScolaA PaynL QuettierT Schield
Thanks for your attention!
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BOLD fMRI Hemodynamic events
Coupling between CBF, metabolism and activation
(? PET-H20, PET-FDG, NIRS)
Stress and Fold Localization in Thin Elastic
MembranesPocivavsek et al. Science 230912-916,
2008
? Why and how do cell swell? A hypothesis
? Phase transition

• Action potentials
• Require cytoskeleton integrity (Matsumoto)
• Cytoskeleton undergoes physical changes (Sato)
• Calcium is critical (Tasaki, 1988)
• Transient cellular expansion (swelling) and
  water influx (Tasaki)
• Transient liberation of heat (23mC Tasaki)

Induction of hemodynamic response (Bold)
(Cold)??
? Water seems to play a central role in cell
activation physiology
Unique feature of action potential initiation in
neocortical neuronsNaundorf et al. Nature
4401060, 2006
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MRI of Neuronal and Glial Swelling as an
indicator of Function in Cerebral Tissue Slices
(Stroman et al. MRM 59 700-706, 2008)
Live cerebral rat slices stimulation with
26mmol K aCSF
Increase in cell water content?(or
 proton-density ? )
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The water molecule
3.2 Å
'Water is H2O, hydrogen two parts, oxygen one,
but there is also a third thing, that makes it
water and nobody knows what it is. D H Lawrence
(1885-1930)
0.9572 Å
105.5 (liquid)
? Liquid water tetrahedral H-bond network with
local defects
Proton mobility (diffusion) decreases with
increase degree of structuring (lower density of
local defects)