IRM fonctionnelle cérébrale:

Bases physiques et biologiques

Denis Le Bihan
Service Hospitalier Frédéric Joliot, UNAF/CEA, Orsay
Magnetic Resonance Imaging…

Strong magnet

Signa LX, SHFJ/CEA, Orsay

 The Magnets…
• Magnetic field strength measured in units of
Gauss or Tesla:
• 1 tesla = 10,000 gauss
• Earth’s magnetic field: 0.5 gauss Signa 3.0T
• Superconducting magnets: filled
with liquid Helium (-269°C)

Profile 0.2T Signa Infinity 1.5T

Ovation 0.35T

Magnex 7.0T
Signa SP 0.5T
OpenSpeed 0.7T
Refrigerator door magnets 0.005T=50G!
Magnetizing tissues …
• Magnetization of atomic nuclei
• Not all nuclei are MRI friendly!
3 Hydrogen 1H (42.6 MHz/T) Body abondance (H20) +++
2 Carbon 12C Æ Carbon 13C (1% of natural carbon)
2 Oxygen 16O Æ Oxygen 17O (5.8 MHz/T)
3 Fluor 19F (40MHz/T)
3 Phosporus 31P (17.2 MHz/T)
1M$/T !

No field Bo field
(thermal equilibrium) (against thermal equilibrium)
M = MH-ML Bo (T) 0.1 0.5 1.5 3…
MH-ML ≈ 1/106 (very weak effect!) E (MHz) 4.3 21 64 125 …
MH-ML α Bo
Magnetic Resonance Imaging…
Radiofrequency
field Tx/Rx Water
(hydrogen nuclei)

Strong magnetic field

Signa LX, SHFJ/CEA, Orsay

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, …)
Getting a signal:
Magnetic Resonance… RF pulses

2-Excitation (transient) Free Induction Decay signals

Ehigh
3-Relaxation

Elow

1-Transmission (short RF pulse 4-Reception

on resonance frequency) (on resonance frequency)
 T1

T2

T2 T2 ++
Playing with basic
contrast (T1, T2)
Magnetic Resonance Imaging…
Radiofrequency
field Tx/Rx Water
(hydrogen nuclei)

Strong magnet Gradient coils

Signa LX, SHFJ/CEA, Orsay

Localizing the MR signal: ω=γGy

Gradient coils… FIELD

GRADIENT:

FREQUENCY ω=γGz

POSITION (Slice selection)

y
SIGNAL
Bo SPECTRUM =
t PROJECTION

z-gradient y-gradient ω
The MRI slice
in k-space
Gx

Gz
Slice selection Gy
ALL COLUMNS CENTRAL 50% OUTER 50%
Image space k-space

ky

kx
K-space sampling strategies
• RADIAL (back-projections)
• LINES (single lines 2D-FT)
• ZIG-ZAG (EPI)
• SPIRAL
• YOUR OWN ….
• « 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

• 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 250 ms 10 mT/m 130 ms 16 mT/m 80 ms

« NEW tricks »: Parallel Imaging (SMASH, SENSE,…)
Simultaneous acquisition of k-space lines
Special phased-array coils: RF hardware

New high resolution

MR detectors

kx

Without SENSE, ETL=48

ky SENSE
reconstruction
ETL=32
Shorter acquisition time with SENSE

The spatial information contained in the component

More SNR,
detectors of anhigher spatial
array are orpartially
used to temporal resolution,
replace spatial
less distortion,
encoding betternormally
which would spatial coverage.
be performed using
gradients
De l’anatomie à la fonction:
Un peu de physiologie...
z Anatomie Fonctionelle macroscopique:
– correlation entre anatomie et fonction (Broca) +++

• Fonctionnement cérébral:
– Cortex/Noyaux gris:
péricaryons, dendrites, synapses
– Substance blanche:
axones myélinisés
– Glie , vaisseaux, ....
Brain of Mr.
Leborgne,
Broca’s patient
 Paramètres d’accès au fonctionnement cérébral
• Biophysique
polarisation dendritique, potentiels d’action,
échanges ioniques --> EEG/MEG
z Neurochimie, neuropharmacologie
(neurotransmetteurs, récepteurs
--> ligands TEP)
z Biologie moléculaire
(canaux ioniques, expression gènes)

z Biochimie: TEP, IRMf, NIRS

métabolisme (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.

Rest Activation

Artery Capillaries Vein CBF CBV Sat O2

 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, H217O (effet direct)

• Agents intravasculaires (+++):

– Origine:
Exogènes: Complexes de Gadolinium (Gd-DTPA)
Endogènes: Déoxyhémoglobine (BOLD)
– Utilisation
IRM 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-Heme
OxyHb: Diamagnetic
DeoxyHb: Paramagnetic ( Hb: Gd-chelate like)

Î DeoxyHb in Red Blood Cells induces a local susceptibility

difference which results in local magnetic field gradients (Thulborn
1982)

Î Effect on nearby tissue

water relaxation
(amplification)
BOLD fMRI: A Historical Perspective ...

z Ogawa et al. (rat), 1990

followed by Turner et al.
(cat): 1991

Hypoxic brain
Effect of RBC DeoxyHb on tissue water relaxation
• Static effect: intravoxel dephasing (α Bo)
– seen on Gradient Echo sequences only

• Dynamic effect: diffusion (α Bo²)

– seen on both GE & SE sequences

Hb MRI Signal
(tissue water)

DeoxyHb: Ì T2*
Hb
Echo signal drop

Hb
TISSUE
Vessel TE
BOLD fMRI: A Historical Perspective ...

Visual stimulation z Kwong al. (human),

followed by Bandettini et al.
(cat), 1992

Rest Activation

Artery Capillaries Vein CBF CBV Sat O2

BOLD fMRI Biophysics: Summary ...

BOLD signal
5.9% 4.4s stimulation BOLD effect
4.9% -is small
3.9% -delayed with respect to stimulus
2.9% onset
1.9% -lasts a few seconds
0.9%
-0.1% Time (s)
-4 -2 0 2 4 6 8 101214161820

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
(venules, larger vessels)

∆R2* = 0.04 {γ∆χ(1-Y)}2 B02 CBV

(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

4
Percent signal change

3 Corresponding eye
stimulation
2

Other eye
1 stimulation

0 4 8 12 16 20 24 28

Time (s)
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)

T
R
BOLD response
mostly 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) 1 volume (2.1 sec)
22 slices 1 TR (3.5 sec)
Auditory
– hear protection mandatory Stimuli

(ears plugs,…) “BEEPS”

– interference with auditory (slices) (silence) (silence) (silence) (silence)

stimuli (language,…)
Ï use of silent interval or
insertion of ‘silent’ sequences
0 2 4 6 8 10 12 14
Time (seconds)
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)

z 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?
Âge
pathologie:MAV,...,
pharmacologie: antihistaminiques?

º Absence de réponse BOLD ???

Word repetition Story Listening Left prefrontal AVM

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, H217O (effet direct)

• Agents intravasculaires (+++):

– Origine:
Exogènes: Complexes de Gadolinium (Gd-DTPA)
Endogènes: Déoxyhémoglobine (BOLD)
– Utilisation
IRM de perfusion clinique (Gd)
fMRI standard (BOLD)

– Mécanisme indirect:
différence de susceptibilité magnétique sang/tissue
 CBV Mapping Using MION
central mono-crystalline
magnetite-like single crystal core
iron oxide agent
crystal 3.94±0.3nm
MION 17.1±0.9nm
Ralph Weissleder
MGH Center for
dextran coating Molecular Imaging Research
 Localization
forepaw stimulation cocaine

BOLD

CBV

J.B. Mandeville, MGH-NMR Center

Diffusion
MRI…

… of water
 DiffusionMagnetic Resonance Imaging (MRI)

Global scale

Meso scale
architecture ? Water
(hydrogen protons)
• Free water: D ≈3 10-9m²/s @ 37°C
<x²>1/2 ≈ 17µm (Td = 50ms)
D
<x 2 > 1/2
17

50 T d 1/2
 RF
Gsel.
Gph-enc.
Gread.

Diffusion sensitized
Half-Fourier Spin Echo EPI
sequence

ADC map
b

ADC
b Dw MRI
Anisotropic
Diffusion
• 1990: Diffusion anisotropy in
brain/spine white matter
• 1992-94: Diffusion Tensor MRI
principles
Mapping cortex connectivity with MR diffusion
(Mangin, Poupon, Cointepas)
Tensor imaging High angular resolution
Bundle crossing

Spin glass models

Infering connectivity matrices

Grasping
Tracking main bundles Tracts + cortical gyri Functional networks
Combining BOLD fMRI and DTI in the cat cortex. Kim and al., 2001
 Combining fMRI + DTI

A B
Receptive
Primary
Expressive Language
Auditory
Language Area Area
Cortex

• A: Fiber bundles originating from Wernicke

• B: Fiber tract between Wernicke and Broca: fasciculus
arcuatus
Courtesy S. Sunaert, Leuwen
Combining fMRI + DTI

Left Right Left Right

words words words words

8
Normal Subject Alexic Patient

Dysconnection (DTI)

Molko, Cohen, Le Bihan, Dehaene et al. JoCN, 2002

z 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