Nuclear Magnetic Resonance Basic Principles NMR Imaging Functional NMR Imaging & Spectroscopy Pierre CARLIER ([email protected]) Laboratoire de RMN AFM/CEA Institut de Myologie Bâtiment Babinski Groupe Hospitalier Pitié-Salpêtrière Paris Cours 1 : Principes de la RMN 1. Magnétisme nucléaire 1.1. Atome 1.2. Moment cinétique 1.3. Moment magnétique 1.4. Rapport gyromagnétique 1.5. Comportement en l’absence et dans un champ statique 1.6. Équation de Larmor 1.7. Noyaux d’intérêt biologique 2. Résonance magnétique nucléaire 2.1. Principe 2.2. Modèle classique (équilibre, excitation) 2.3. Angle de bascule 2.4. Modèle quantique 2.4. Signal de RMN : signal d’induction libre (FID) 3. Phénomène de relaxation 3.1. Relaxation 3.2. Longitudinale (T1) 3.3. Transversale (T2) 3.4. Notion de T2* 4. Mesure du signal RMN 4.1. Aimant/sonde RMN 4.2. FID 4.3. Inversion-récupération : mesure du T1 4.4. Écho de spin: mesure de T2 5. Contraste tissulaire 5.1. contraste T1 5.2. contraste T2 5.3. contraste densité de protons 6. Spectroscopie RMN 6.1. déplacement chimique 6.2. l’exemple de la RMN du P31 Magnetic properties of the nuclei Matter is made of atoms. Atoms are made up of electrons and nuclei. Each atomic nucleus has four important physical properties: mass, electric charge, magnetism and spin. spin Magnetic properties of the nuclei Matter is made of atoms. Atoms are made up of electrons and nuclei. Each atomic nucleus has four important physical properties: mass, electric charge, magnetism and spin. Spin is a quantum mechanical intrinsic property of elementary particles. It is very difficult to imagine this property, and the notion of actual rotation can be somewhat helpful. However, it is wise to separate this notion of a spinning particle from the quantum mechanical property we call "spin". Magnetic properties of the nuclei Matter is made of atoms. Atoms are made up of electrons and nuclei. Each atomic nucleus has four important physical properties: mass, electric charge, magnetism and spin. Spin is a quantum mechanical intrinsic property of elementary particles. It is very difficult to imagine this property, and the notion of actual rotation can be somewhat helpful. However, it is wise to separate this notion of a spinning particle from the quantum mechanical property we call "spin". Although spin is a form of angular momentum, an elementary particle with spin does not mean it is rotating; particles with spin simply have spin. The concept of a particle rotating around its own axis is helpful, but it is intellectually sterile; for example, at absolute zero temperature when all motion ceases, a particle still has "spin". Moment cinétique Cette rotation individuelle induit ceque l’on appelle un moment cinétique de spin ou moment angulaire noté j n Moment cinétique: j r v j rp m.r V m.r.V .n Avec Proton: •Charge = e •Masse : m= 1.673x10-27 kg p quantité de mouvement V vitesse de rotation, r vecteur position, n axe de rotation Moment magnétique Moment magnétique: Si la particule en rotation est chargée, alors la rotation de sa distribution de charge induit ce que l’on appelle un moment magnétique de spin, noté µ n S .I .n N ; V .r 2 . I e. N e . j V 2 .r Avec r v I courant équivalent S surface apparente V vitesse de rotation, pulsation, n axe de rotation , normale à la Proton: •Charge = e =1.6x10-19 C 2 r •Surface apparente: S= surface S N nbre de tours par seconde (fréquence de rotation) Rapport gyromagnétique On obtient: j Moment magnétique: r v q.V .r .n 2 Moment cinétique: j m.r.V .n Les protons s’apparient entre eux de sorte que leurs aimantations s’annulent 2 à 2. Seuls les atomes à nombre de nucléons impairs (=> 1 nucléon non apparié) possèdent un moment magnétique intrinsèque non nul. e j 2m Rapport gyromagnétique, propre à chaque noyau Comportement en l’absence de champ magnétique externe Vecteur aimantation macroscopique M B0 = 0 Mx = My = Mz = 0 Les moments magnétiques (µ) des atomes soumis à un très faible champ magnétique extérieur ont des orientations aléatoires: L’aimantation macroscopique résultante est nulle. Comportement dans un champ magnétique externe B0 B0 intense l’orientation des spins parallèlement à B0. En fait, B0 impose un couple au moment magnétique : X B0 Ils se séparent en 2 populations tournant autour de B0 avec un B0 0 angle fixé (PRECESSION), soit Mx =My=0 dans la même direction que lui Mz = M0 (parallèle) soit dans la direction opposée (antiparallèle), en raison de phénomènes relevant de la Sous l’action d’un champ B0 0 appliqué dans la mécanique quantique. direction Z, tous s’alignent selon Z, répartis dans le sens parallèle UP ou anti-parallèle DOWN de sorte que l’aimantation résultante est non nulle. Interaction with the magnetic field B0 Spin precession The direct relationship between the magnetic moment (μ) and the spin angular momentum (J) is, from experiment J When this magnetic moment is in the presence of an external magnetic field B0 it experiences a torque and precesses around the B0 field with an angular frequency 0 (the “Larmor frequency”): d B0 dt B0 0 Équation de Larmor La pulsation ou vitesse de précession dans un champ magnétique statique est définie par la relation de Larmor: 0 B0 Interaction with the magnetic field B0 Spin precession B0 0 Interaction with the magnetic field B0 Spin precession spin Interaction with the magnetic field B0 A selection of nuclear isotopes and their properties. Interaction with the magnetic field B0 © 2006 Denis Hoa et al, Campus Medica. www.e-mri.org Modèle quantique A L’EQUILIBRE dans un champ B0 D’un point de vue énergétique: état UP état DOWN (parallèle) (anti-parallèle) = Basse énergie E E= hB0 = Haute énergie E2=+hB0/2 Excédent =M0 E1 =-hB0/2 Macroscopic magnetization Quantum Description: Bo > 0 E 0 Bo When placed in an external magnetic field, the direction of angular momentum arising from nuclear spin is quantized (it can only take certain values). This results in discrete energy states. (Without an external magnetic field these states collapse into one state.) Note that Zeeman splitting is a quantum mechanical effect, and without it MRI and NMR would not exist. Macroscopic magnetization The equivalent population difference which occurs between the two energy states results in the net magnetization in a sample. N N 0 B0 spin excess N N 2kT 2kT 1.05 10 34 Joule s k 1.38 10 23 Joule/K N N 10 10 ppm N N 1000000 T 300 K B0 3 Tesla 2.68 10 rad/s 8 M0 0 2 2 4kT B0 Continuous wave (CW) experiment Continuous wave (CW) experiment Continuous wave (CW) experiment Continuous wave (CW) experiment 40 MHz 900MHz, 21.2 T NMR Magnet at HWB-NMR, Birmingham, UK being loaded with a sample Interaction with B1 Classical Description Rotating Frame 0 To simplify the vector description, the X,Y axis rotates about the Z axis at the Larmor frequency 0 Interaction with B1 Classical Description Rotating Frame B1 << B0 B1 x’ y’ B1 is an oscillatory magnetic field with angular frequency = 1 B1 is stationary in the rotating frame Interaction with B1 Classical Description Rotating Frame µ B1 << B0 B1 x’ y’ In the presence of an external magnetic field B1, experiences a torque (in the rotating frame) d B1 dt ' Interaction with B1 A B1 field applied for a finite time is called an “rf pulse”. Suppose the rf field in turned on (quickly) to a constant value B1x’ for a time interval and the is rapidly turned off. In the rotating frame, the net magnetization will rotate through the angle : B1 For example, the size of B1 required for a 90° flip angle over 1.0 ms is 5.9 T for protons. Interaction with B1 Classical Description A B1 field applied for a finite time is called an “rf pulse”. Suppose the rf field in turned on (quickly) to a constant value B1x’ for a time interval and the is rapidly turned off. In the rotating frame, the net magnetization will rotate through the angle : B1 Mz + Mxy Modèle quantique EXCITATION Déséquilibrer le système induire des transitions de l’état bas (E2) vers l’état haut (E1) Fournir l’énergie nécessaire via une onde électromagnétique: E=hr=E transition d’état + MISE EN PHASE des spins E= hB0 E E2 E1 B1 Le champ externe B0 Il faut générer un champ fort et stable. Aimant résistif Aimant supraconducteur - Consommation courant, B0<0.3T, + peu cher Pour l’IRM in vivo, Bo vaut de 0.5 Tesla (homme) à 11 Tesla (souris) -- cher!! Installation/ conso liquides cryogéniques (He, N2) + + stables, B0 élevés, faible conso de courant Champ magnétique terrestre b = 5. 10-5 Tesla Sonde RMN La sonde RMN va produire le champ RF d’excitation et lire le signal de relaxation dans le plan transversal (0xy). z B0 B1 O x y Circuit d’accord-adaptation r Émetteur/récepteur CM Re RF CT L Boucle d’induction Réglage d’adaptation C M CT r Re Réglage d’accord f circuit 1 LCT NMR Signal A rotating magnetic moment generates a rotating magnetic field. It is possible to detect this oscillating field using a wire coil. NMR Signal The oscillating electric current induced by the precessing nuclear transverse magnetization is called the NMR signal or free-induction decay (FID) Signal de précession libre:Free Induction Decay (FID) 90 acquisition t S(t) S0 exp( * ) T2 Relaxation Return to equilibrium of net magnetization is called relaxation. Relaxation combines 2 different mechanisms: Longitudinal relaxation corresponds to longitudinal magnetization recovery Transverse relaxation corresponds to transverse magnetization decay M does not simply "rotate" back to M0, because the longitudinal and transverse relaxation are separate. Relaxation Longitudinal relaxation (T1) Longitudinal magnetization precessing protons are pulled back into alignment with main magnetic field (B0) M z (t ) M z (1 e t T1 ) Relaxation The T1 time is related to the transfer of energy from a nuclear spin system to its environment ("lattice“). The transfer of energy to the "lattice" is not spontaneous—T1 "relaxation" can only occur when a proton encounters an oscillating magnetic field at (or near) the Larmor frequency. The frequency of the oscillating magnetic field a molecule produces is dependent on how fast it moves (rotation, translation, vibration). The source of such a field is other protons in the same molecule or in different molecules. Relaxation Longitudinal relaxation (T1) Relaxation Transverse relaxation (T2) Transverse magnetization precessing protons become out of phase leading to a drop in the net magnetic moment vector M x (t ) M x e t T2 time Relaxation Relaxation The T2 time is related to the effect of nuclear spins on each other. The spinspin interaction purely refers to the loss of phase coherence of spins as they interact with each other via their own oscillating magnetic fields. (Phase coherence means spins are all precessing together.) The slight changes in magnetic field which a proton experiences causes its Larmor frequency to change. As a result, the precession of spins moves out of phase and the overall net magnetization is reduced. NMR Signal acquisition methods NMR Signal acquisition methods 1-2 NMR Signal acquisition methods Écho de spin: principe 90° e 180° t /T2* e t /T2 x y L’aimantation M est basculée dans le plan xy Inhomogénéités fixes de B0=> déphasage des µ Inhomogénéités fixes de B0=> le déphasage se poursuit L’aimantation est refocalisée NMR Signal acquisition methods Contrast Ability to distinguish different tissues from one another. Contrast Ability to distinguish different tissues from one another. Contrast T1 weighted images short T1 Signal long T1 maximal contrast TR Contrast Signal T2 weighted images short T2 long T2 maximal contrast TE Contrast weighted images =1 =1 Signal Signal = 0,8 TR = 0,8 TE