IRM fonctionnelle cérébrale - sorbonne-universite · IRM de perfusion clinique (Gd) fMRI standard...
Transcript of IRM fonctionnelle cérébrale - sorbonne-universite · IRM de perfusion clinique (Gd) fMRI standard...
IRM fonctionnelle cérébrale:Bases physiques et biologiques
Denis Le BihanService Hospitalier Frédéric Joliot, UNAF/CEA, Orsay
Magnetic Resonance Imaging…
Signa LX, SHFJ/CEA, Orsay
Strong magnet
The Magnets…
Signa 3.0T
Signa Infinity 1.5T
Ovation 0.35T
Signa SP 0.5T
Refrigerator door magnets 0.005T=50G!
• Magnetic field strength measured in units of Gauss or Tesla:
• 1 tesla = 10,000 gauss• Earth’s magnetic field: 0.5 gauss• Superconducting magnets: filled
with liquid Helium (-269°C)
Profile 0.2T
Magnex 7.0T
OpenSpeed 0.7T
Magnetizing tissues …• Not all nuclei are MRI friendly!
Hydrogen 1H (42.6 MHz/T) Body abondance (H20) +++Carbon 12C Carbon 13C (1% of natural carbon)Oxygen 16O Oxygen 17O (5.8 MHz/T)
Fluor 19F (40MHz/T)
Phosporus 31P (17.2 MHz/T)
No field Bo field (thermal equilibrium) (against thermal equilibrium)
Bo (T) 0.1 0.5 1.5 3 …E (MHz) 4.3 21 64 125 …
M = MH-MLMH-ML ≈ 1/106 (very weak effect!)MH-ML α Bo
1M$/T !
• Magnetization of atomic nuclei
Magnetic Resonance Imaging…
Signa LX, SHFJ/CEA, Orsay
Strong magnetic field
Water(hydrogen nuclei)
Radiofrequency field Tx/Rx
RF coils…• Must be as close as possible to the object to image
(filling factor)• 3 types of coils:
• Transmit/receive (linear, quadrature)(body, head quadrature coils, knee coil …)
• Receive only (surface coils)(all purpose coils, breast coils, …)
• Phased array coils(cardiac/torso, spine, vascular coils, …)
Ehigh
Elow
1-Transmission (short RF pulse on resonance frequency)
RF pulses
Free Induction Decay signals
Getting a signal:Magnetic Resonance…
2-Excitation (transient)
3-Relaxation
4-Reception (on resonance frequency)
T1
T2
T2 T2 ++Playing with basic contrast (T1, T2)
Magnetic Resonance Imaging…
Signa LX, SHFJ/CEA, Orsay
Strong magnet
Water(hydrogen nuclei)
Gradient coils
Radiofrequency field Tx/Rx
Bo
z-gradient y-gradient
z
y
FREQUENCY
POSITION
SIGNAL
FIELD GRADIENT:
ω = γ G z
t
Localizing the MR signal:Gradient coils…
SPECTRUM =PROJECTION
ω
(Slice selection)
ω = γ G y
ALL COLUMNS CENTRAL 50% OUTER 50%
ky
kx
GzSlice selection
Gx
Gy
The MRI slice in k-space
Image space k-space
K-space sampling strategies
• « OLD style »• Switch from Spin-Echo to Gradient-Echo• Partial k-space sampling
(Half or partial Nex, rectangular FOV,…)
• « MODERN tricks »• Several echoes (lines) per shot (EPI, FSE,…)• Fast gradient hardware
• RADIAL (back-projections)• LINES (single lines 2D-FT)• ZIG-ZAG (EPI)• SPIRAL• YOUR OWN ….
• ISSUES: GRADIENT PERFORMANCE+++• Speed/Resolution• Artifacts (motion, reconstruction)• Contrast, SNR
EPI: Practical issues
• Sensitive to field gradient artifacts (eddy currents, susceptibility interfaces)– geometric distortion (anatomical localization of activation foci)– signal drop-out (frontal and temporal poles)
5 mT/m 10 mT/m 16 mT/m 80 ms130 ms250 ms
New high resolutionMR detectors
SENSE reconstruction
Without SENSE, ETL=48
ETL=32Shorter acquisition time with SENSE
kx
ky
« NEW tricks »: Parallel Imaging (SMASH, SENSE,…)Simultaneous acquisition of k-space linesSpecial phased-array coils: RF hardware
The spatial information contained in the component detectors of an array are used to partially replace spatial encoding which would normally be performed using gradients
More SNR, higher spatial or temporal resolution, less distortion, better spatial coverage.
De l’anatomie à la fonction:Un peu de physiologie...
Brain of Mr. Leborgne, Broca’s patient
Anatomie Fonctionelle macroscopique:– correlation entre anatomie et fonction (Broca) +++
• Fonctionnement cérébral:– Cortex/Noyaux gris:
péricaryons, dendrites, synapses – Substance blanche:
axones myélinisés– Glie , vaisseaux, ....
Paramètres d’accès au fonctionnement cérébral• Biophysique
polarisation dendritique, potentiels d’action,échanges ioniques --> EEG/MEG
Neurochimie, neuropharmacologie(neurotransmetteurs, récepteurs--> ligands TEP)
Biologie moléculaire(canaux ioniques, expression gènes)
Biochimie: TEP, IRMf, NIRSmétabolisme (présynaptique)--> (CMRglu, CMRO2, ... ? CBF)
• Imagerie--> Choix des paramètres à mesurer/imager--> Limites de la résolution temporelle et spatiale--> Définit le caractère non invasif, simplicité, coût
FMRI (PET)Neuronal activation ⇐⇒ Metabolism ⇐⇒ Blood Flow
..."The brain possesses an intrinsic mechanism by which its vascular supply can be varied locally in correspondence with local variations of functional activity"...
Roy, C.W. & Sherrington, C.S. J Physiol 1890, 11: 85-108.
Sat O2CBF CBVArtery Capillaries Vein
ActivationRest
Functional MRI: The Hemodynamic Filter
• Indirect reflect of neuronal activity– neurovascular (un)coupling?
CMRO2 < CRMglu << CBF,CBV– Origin? Mechanism? Adapted from Magistratti et al.
IRM et Perfusion cérébrale• Traceurs diffusibles: 19F, D2O, H2
17O (effet direct)
• Agents intravasculaires (+++): – Origine:
Exogènes: Complexes de Gadolinium (Gd-DTPA)Endogènes: Déoxyhémoglobine (BOLD)
– UtilisationIRM de perfusion clinique (Gd)fMRI standard (BOLD)
– Mécanisme indirect: différence de susceptibilité magnétique sang/tissue
Blood Oxygen Level Dependent(BOLD)Contrast- Theory -
BOLD fMRI Physics
• Magnetic status of Hemoglobin in RBC: (O2)-Fe-HemeOxyHb: DiamagneticDeoxyHb: Paramagnetic ( Hb: Gd-chelate like)
DeoxyHb in Red Blood Cells induces a local susceptibility difference which results in local magnetic field gradients (Thulborn1982)
Effect on nearby tissue water relaxation (amplification)
BOLD fMRI: A Historical Perspective ...
Ogawa et al. (rat), 1990 followed by Turner et al. (cat): 1991
Hypoxic brain
Effect of RBC DeoxyHb on tissue water relaxation
Hb
Hb
Hb
TISSUEVessel
• Dynamic effect: diffusion (α Bo²)– seen on both GE & SE sequences
Echo signal drop
MRI Signal(tissue water)
TE
DeoxyHb: T2*
• Static effect: intravoxel dephasing (α Bo) – seen on Gradient Echo sequences only
BOLD fMRI: A Historical Perspective ...
Kwong al. (human), followed by Bandettini et al. (cat), 1992
Visual stimulation
Sat O2CBF CBVArtery Capillaries Vein
ActivationRest
BOLD fMRI Biophysics: Summary ...
-0.1%0.9%1.9%2.9%3.9%4.9%5.9%
-4 -2 0 2 4 6 8 10 121416 1820Time (s)
BOLD signal4.4s stimulation BOLD effect
-is small-delayed with respect to stimulus onset-lasts a few seconds
BOLD (susceptibility) effect increases with Bo, better seen with gradient-echoes than spin-echoes
BOLD Imaging=vessel imaging!∆R2* = 4.3 γ∆χ(1-Y) B0 CBV
∆R2* = 0.04 {γ∆χ(1-Y)}2 B02 CBV
(venules, larger vessels)
(smaller capillaries)Ogawa et al., Biophys. J., 64:803-812, 1993
• Effets champ, séquence, taille vaisseaux(Weisskoff):
»composante ‘petits vaisseaux’(<30µm):diffusion ++, varie avec Bo², visible SE
(TEopt=T2)»composante ‘macrovaisseaux’
déphasage statique ++, varie avec Bo, visible GE>ASE>SE (TEopt=T2*)
High Resolution at 4 Tesla
0
1
2
3
4
0 4 8 12 16 20 24 28
Time (s)
Perc
ent s
igna
l cha
nge Corresponding eye
stimulation
Other eyestimulation
Ocular dominance columns
University of Western Ontario
Drive to Higher Field
• Conventional field strength: 1.5 Tesla• High field systems: 2 Tesla - 4.7 Tesla• Ultra high field systems: 7, 8, 9.4,… Tesla
Blood Oxygen Level Dependent(BOLD)Contrast
- Practical matters -
BOLD fMRI: …which MRI sequence?
• Requirement: Ultra-fast imaging +++– to follow the hemodynamic response (TR=2-3 s)– with whole brain coverage (30+ slices)– robust to motion artifacts (single shot sequence)
TR
BOLD responsemostly used sequence = Echo-Planar Imaging (EPI)
EPI: Practical issues (1)• Optimization of EPI sequence:
– TE ≈ brain tissue T2* (60ms @ 1.5T, 35ms @ 3T)– voxel size: isotropic (typically 2-4mm)– data echo train: as short as possible (half-Fourier, …)
• Artifacts +++ (distorsion, signal drop-out)• Gradient switching is extremely noisy (100+
dB)
– hear protection mandatory (ears plugs,…)
– interference with auditory stimuli (language,…)use of silent interval or insertion of ‘silent’ sequences
0 2 4 6 8 10 12 14
(silence) (silence) (silence) (silence)
1 volume (2.1 sec) 22 slices 1 TR (3.5 sec)
Time (seconds)
AuditoryStimuli
“BEEPS” (slices)
Patient set-up +++
• Stimulation hardware– vision, audition, taste, ….– Compatible by MRI equipement– Synchronization with MRI scanner
• Task performance control– Mouse/joystick (yes/no response, reaction times)– Eye motion recording, EEG,...
Le filtre hémodynamique
• Résolution limitée– Résolution spatiale (réseau vasculaire)
» Selon le compartiment vasculaire (mm3)(artériole, capillaire, vénule)
– Résolution temporelle limitée (régulation vasculaire)» Réponse hémodynamique (secondes)
Relation avec l’activation
– Linéarité? (stim. paramétriques, multiples ou rapprochés)
– Effets toniques/transitoires ? (stimuli longs)– Seuil? (stimuli brefs ou faibles)
Imagerie Neurofonctionnelle:Le filtre hémodynamique
• Réflexion indirecte de l’activité neuronale– Mécanisme?
recrutement capillaire, vitesse de circulation– Régulation?
neurogène, neuromédiateur, NO,...– Couplage réponse BOLD/ neurophysiologie: relation
complexe (biologie ET physique: résolution, Bo,…)
– Variations?Âgepathologie:MAV,..., pharmacologie: antihistaminiques?
Absence de réponse BOLD ???
Left prefrontal AVMStory ListeningWord repetition
Before embolization
After embolization
S. Lehéricy et al., Radiology
Interprétation des données IRMf
• Régions ‘silencieuses’?– seuils statistiques
• Régions ‘activatées’?– rôle réel dans une fonction cognitive
• Précision anatomique?– Position/extension des foyers activés– Corrélation avec l’électrophysiologie
(moteur, language, ...)
BONUS- Agents de contraste –
- IRM de diffusion -
IRM et Perfusion cérébrale• Traceurs diffusibles: 19F, D2O, H2
17O (effet direct)
• Agents intravasculaires (+++): – Origine:
Exogènes: Complexes de Gadolinium (Gd-DTPA)Endogènes: Déoxyhémoglobine (BOLD)
– UtilisationIRM de perfusion clinique (Gd)fMRI standard (BOLD)
– Mécanisme indirect: différence de susceptibilité magnétique sang/tissue
CBV Mapping Using MION
dextran coating
central mono-crystallinemagnetite-like single crystal core
iron oxide agentcrystal 3.94±0.3nmMION 17.1±0.9nm
Ralph WeisslederMGH Center forMolecular Imaging Research
Localizationforepaw stimulation cocaine
BOLD
CBV
J.B. Mandeville, MGH-NMR Center
Diffusion MRI…
… of water
Water (hydrogen protons)
Magnetic Resonance Imaging (MRI)Diffusion
• Free water: D ≈3 10-9m²/s @ 37°C <x²>1/2 ≈ 17µm (Td = 50ms)
<x2>1/2
Td1/2
D
50
17
Global scale
Meso scale architecture ?
b
S
b
ADC
Diffusion sensitized Half-Fourier Spin Echo EPI
sequence
RF
Gsel.Gph-enc.
Gread.
ADC map
Dw MRI
AnisotropicDiffusion
• 1990: Diffusion anisotropy in brain/spine white matter
• 1992-94: Diffusion Tensor MRI principles
Mapping cortex connectivity with MR diffusion(Mangin, Poupon, Cointepas)
Tracts + cortical gyri
Infering connectivity matrices
Functional networks
Grasping
Tensor imaging
Tracking main bundles
High angular resolutionBundle crossing
Spin glass models
Combining BOLD fMRI and DTI in the cat cortex. Kim and al., 2001
Combining fMRI + DTI
A BPrimary Auditory CortexReceptive Language AreaExpressive Language Area
• A: Fiber bundles originating from Wernicke• B: Fiber tract between Wernicke and Broca: fasciculus
arcuatusCourtesy S. Sunaert, Leuwen
Dysconnection (DTI)
Leftwords
Rightwords
Normal Subject
Combining fMRI + DTI
Alexic Patient
Leftwords
Rightwords
Molko, Cohen, Le Bihan, Dehaene et al. JoCN, 2002
For their contribution:(Lab. of Anatomical and Functional Neuroimaging, SHFJ/CEA, Orsay)– H. Chabriat , S. Pappata & N. Molko– C. Clark, N. Lori– A. Darquie, I. Klein– S. Chabert, C. Mecca– S. Dehaene and coll.– L. Hertz-Pannier & C. Chiron– F. Lethimmonier, E. Giacomini– J.F. Mangin, D. Papadopoulos, D.
Rivière, C. Poupon,Y. Cointepas– J.B. Poline, Ph. Ciuciu, F. Kherif &
A.L. Paradis