Magnetic Resonance Imaging

Transcription

1 Magnetic Resonance Imaging The Basics Content MR and other modalities MR Principle and Recipe Hardware Basic Physics Contrasts Image Formation Examples Hans Wehrl - MRI Basics PRIMA IV 1

2 Dedicated Imaging Modalities Optical CT MRI PET Imaging Morphology Morphology (Function) Function Function Modern Imaging Technologies and their Limitations Anatomy Physiology Metabolism Molecular Micro CT Ultrasound MRI SPECT Micro PET Optical Autoradiography Histology INVASIVE Hans Wehrl - MRI Basics PRIMA IV 2

3 MR Principle MR is very simple: N S appx. 65% H 2 O Recipe for MRI 1) Put subject in big magnetic field (leave him there) N 2) Transmit radio waves into subject [about 3 ms] 3) Turn off radio wave transmitter S 4) Receive radio waves re-transmitted by subject Manipulate re-transmission with magnetic fields during this readout interval [ ms: MRI is not a snapshot] 5) Store measured radio wave data vs. time Now go back to 2) to get some more data 6) Process raw data to reconstruct images 7) Allow subject to leave scanner (this is optional) Hans Wehrl - MRI Basics PRIMA IV 3

4 History of NMR 1952: Nobel prize in physics for Bloch and Purcell 1977: N Damadian: first human MRI S 1990: Ogawa: fmri 1946: F. Bloch & E. Purcell: atomic nuclei absorb and reemit radio frequency energy 1970s: Lauterbur & Mansfield: first images by use of Gradients 1982: Clinical 1.5 T MRI early 1980s: NMR MRI: Why the name change? most likely explanation: nuclear has bad connotations Necessary Hardware Magnet Gradient Coils RF Coil RF Amp. G x G y G z RF Coil Scanner Electronics Gradient Coils Magnet Computer Hans Wehrl - MRI Basics PRIMA IV 4

5 Necessary Hardware Magnet RF Coils Gradient coil E=1/2*L*I 2, can be around 80 MJ for 7 to 9T WB systems Safety The enormous strength of the magnet makes safety essential! Things fly ~ even big things! Source: Simplyphyiscs Make sure you are aware of the hazards. Screen yourself every time before entering the scanner room for metallic objects. Hans Wehrl - MRI Basics PRIMA IV 5

6 Safety Things fly ~ even big things e.g. oxygen bottles! MR Physics Can measure only certain nuclei: 1 H, 13 C, 19 F, 23 Na, 31 P (and others) N 1 H (proton) abundant: high concentration in human body or in animals (water!) high sensitivity: yields large signals Hydrogen ion is positively charged Spin: A particle rotating upon its own axis Electrons, protons and neutrons spin Spinning, charged particles are magnetic Hans Wehrl - MRI Basics PRIMA IV 6

7 MR Physics Animal + Magnet: Without magnetic field: S N With magnetic field: S N N N M No net magnetization Spins randomly oriented Applied magnetic field S Low net magnetization only % of protons/t align with field Energy levels are quantized E spin-down Boltzmann B spin-up According to quantum mechanics a proton in a magnetic field has two spinstates with a well-defined energy (energy eigenstates), typically called spin-up and spin-down. Hans Wehrl - MRI Basics PRIMA IV 7

8 Spin eigenstates S B 0 M #Eigenstates=2I+1 for I=0.5 (Protons) #Eigenstates=2 ( spin up spin down ) B 0 It is very tempting to make drawings like this. N However these are not very useful and probably even wrong. Spin eigenstates Eigenstates: Eigenstates form a basis for all possible states Quantum mechanics: complex numbers that determine direction in space - If we would measure the direction of 1 spin along the magnetic field, we would measure either spin-up or spin-down (but this we never do with MRI!) - The direction of spins are associated with some intrinsic uncertainty (Heisenberg) - If we consider a large number of spins, the uncertainty disappears and we can consider one large net magnetic moment M 0, which can have arbitrary well-defined directions in space. Hans Wehrl - MRI Basics PRIMA IV 8

9 MR Physics Magnet Gradient Coils N RF Coil RF Coil Gradient Coils Magnet 0.1x0.1x0.1 mm 3 =1*10-9 L voxel contains 3.35 x molecules [water] = 55.6 Mol/liter It makes no sense to look at individual spins. We have to consider large number of spins simultaneously Macroscopic volumes and Ehrenfest Theorem bring us back to classical physics Many spins in a magnetic field spin up eigenstates > spin down eigenstates S N N M Applied magnetic field S Hans Wehrl - MRI Basics PRIMA IV 9

10 MR Physics Animal + Magnet -> PrecessionN Similar to: Spinning top in gravitational field Precession axis Spin axis Gravitational field Magnetic field Gravitation + Mass + Spin = Precession Magnetic field + Magnetic Moment + Spin = Precession MR Physics Resonance Principle : Angular momentum from spinning (J) + Magnetic moment (µ) + External magnetic field (B) = Precession ( ) Precession (Larmor) Frequency * B = B = Gyromagnetic Ratio (depends on nuclei, e.g. protons: 42 MHz/T) Magnetic Field Strength Hans Wehrl - MRI Basics PRIMA IV 10

11 MR Physics Animal + Magnet + Radio Frequency: Excitation Signal RX coil Resonance Energy transfer Signal induction in coil MR Physics Longitudinal Relaxation Time T1 and TR Longitudinale Relaxation = Energy transfer between excited spins and Tissue (Spin-Lattice-Relaxation) Reestablishing of longitudinal (B 0 ) magnetization with time constant T1 TR (repetition time) = time to wait after excitation before sampling T1 Hans Wehrl - MRI Basics PRIMA IV 11

12 MR Physics Transverse Relaxation Time: in phase precession out of phase precession S M xy time S M xy RX RX N MR Signal N MR Signal Over time the transversal magnetization M xy decays precession at slightly different frequencies (like clocks) because of (1) random fluctuations in the local field at the molecular level T2 and T2* (2) larger scale variations in the magnetic field ->T2* MR Physics Transverse Relaxation Time T2 and TE Transverse Relaxation = Decay of magnetization by interaction between nuclei (Spin-Spin-Relaxation) TE (time to echo) = time to wait to measure T2 or T2* (after refocusing with spin echo or gradient echo) Hans Wehrl - MRI Basics PRIMA IV 12

13 MR Physics Spin Echo: add an 180 RF Pulse Transverse relaxation T2* is faster than T2 Echo of signal by 180 o pulse to measure T2 MR Physics Relaxation times are tissue specific: M z TR=repetition time TE=echo time Signal Tissue 1 Tissue 1 Tissue 2 Tissue 2 TR t Short TE Medium TE Long TE t Longitudinal Relaxation Transversal Relaxation Hans Wehrl - MRI Basics PRIMA IV 13

14 Contrasts MR Signal of a typical Sequence: For TR>>TE S SE ( TE, TR ) TR 1 exp T 1 exp TE T 2 Image weigthings with focus on spin density, the spin-lattice relaxation time T 1 or the spin-spin-relaxation time T 2 can be achieved via echo time (TE) and repetition time (TR) settings TR PD T1 T TE (Values for appx. 1 Tesla) Image Formation Where inside the magnet did the Signal come from? Spatial Encoding: Gradients 1st Dimension: excite only frequencies corresponding to slice plane Freq B o - B B o + B Field Strength (T) ~ z position 2nd & 3rd Dimension: Frequency left-right: frequency encode top-bottom: phase encode Phase Hans Wehrl - MRI Basics PRIMA IV 14

15 Image Formation Pulse Sequence RF Slice Selection Gradient G S Phase Encoding Gradient G Frequency Encoding Gradient G f MR-Signal Image Formation: After slice selection RF G S G G f MR-Signal 9 Voxel Spins in Plane right after 90 Pulse and Slice Selection Precession with same Frequency Phase encoding Gradient G in x-direction G f MR Signal Phase encoding Gradient G Frequency encoding G f turned on off, but phase differences remain in y-direction Hans Wehrl - MRI Basics PRIMA IV 15

16 Fourier Transform: Basic Fourier Series: decompose periodic functions or signals into the sum of simple oscillating functions (sin & cos) e.g. Square-function, the infinite slopes lead to many frequencies involved: A t A f Fourier Transform: Basic Fourier Transform: allows us to get from Signal(t) space to go to the Signal(f) space and vice versa Time domain FT Frequency domain Lightning Impulse or -funtion FT Boxcar sinc function: sin(x)/(x) FT Mexican Hat Potential Tuning fork sin wave Hans Wehrl - MRI Basics PRIMA IV 16

17 Image Formation Fourier Transform Phase Our Object time Raw Data Phase Phase Phase Freq (x) FT in Frequency domain x FT in Phase Domain y Example 2 y Example 1 time Freq (x) x Image Formation Fourier Transform Phase Phase y Example 3 Our Object time Raw Data Freq (x) FT in Frequency domain x FT in Phase Domain Peak height is converted to image intensity Hans Wehrl - MRI Basics PRIMA IV 17

18 Image Formation Fourier Transformation Phase y Frequency x k-space: Every point contains information of the entire image Image Formation pulse sequence: series of excitations, gradient triggers and readouts Echos refocusing of signal RF Pulse Slice Phase Spin echo: 180 degree pulse to mirror image the spins in the transverse plane measure T2 ideally TE = average T2 Frequ. MR Signal 1st Echo 2nd Echo Gradient echo: flip the gradient from negative to positive -> echo measure T2* ideally TE ~ average T2* Hans Wehrl - MRI Basics PRIMA IV 18

19 Image Formation Spin Echo Acquisition Time: T ac = TR N Ph N Acquisitions TE/2 TE/2 TR RF Pulse MR Signal FID Echo Phase Gradient N Ph Image Formation Sequences Zoo: 1 0 SE GR E Gradient Echo Percentage / % 128 # Echoes TS E HASTE Hybrid Sequences GRASE / TGSE / Multishot EPI single-shot TGSE EP I Hans Wehrl - MRI Basics PRIMA IV 19

20 RF Coils: Voltage and SNR induced in coil The voltage induced in the MR receiver coil can be calculated using Faraday`s law of induction B RX coil with take describes coil sensitivity amplifier then and since Voltage induced in coil: Signal-to-noise-ratio: Geometric sensitivity of the RF coil Magnet Gradient Coils N RF Coil RF Coil Gradient Coils Magnet Signal =1 =0 z-axis position Hans Wehrl - MRI Basics PRIMA IV 20

21 Geometric coil sensitivity N volume coil - homogenous - large field of view - sensitive surface coil - small field of view - inhomogenous Parallel imaging N 32 channel head array coil, MGH array coils - higher sensitivity - higher speed: parallel imaging acceleration (GRAPPA, SENSE) i.e. use coil position information to increase imaging speed Hans Wehrl - MRI Basics PRIMA IV 21

22 Cover the body with multiple coils 7T-Birdcage N FA-Map 7T-B 1 -Shim FA-Map Siemens Medical Parallel RX-coils: increase SNR and imaging speed Parallel TX-coils: reduce RF deposition, increase B 1 field homogeneity Noninvasive imaging of small animals 1.2 Rat Human Sensitivity % 63% % 0.1mm Resolution 100% 1mm - Enhance source signal (e.g. contrast agents, hyperpolarization etc.) - optimize signal detection (e.g. MRI coils) - but usually: longer imaging times for small animals Hans Wehrl - MRI Basics PRIMA IV 22

23 Limits of MRI-resolution In principle resolution is only limited by: -diffusion - Relaxation times (T2) - movement - available time Mansfield and Morris (1982): with: f=300 MHz time=3600 s S/N=25 x=35 µm T 1 /T 2 =30 V c =1.5 cm Cryo-coils Induced MRI Signal: Induced Coil Noise: for small sample volumes the coil noise dominates: Solution: cool down the MRI coil SNR increase: ca. 2.5 Baltes et al. NMR Biomed (2009) Bruker BioSpin MRI Hans Wehrl - MRI Basics PRIMA IV 23

24 Signal Processing schematic RF coil (TX/RX) pulse programmer RF amplifier duplexer amplifier high frequency ADC filter computer ADC filter demodulator low frequency Signal Demodulation (Mixing) MR signal: demodulation signal: Mixing: RF-Mixer remove high frequencies with BP high frequency MR signal 0 BP CO frequency typically in the range of -1 MHz to 1 MHz -> further signal processing demodulation signal 1 Hans Wehrl - MRI Basics PRIMA IV 24

25 Contrast Agents Why? Enhance contrast (of course ), Evaluate physiological parameters (Perfusion), Tumor diagnostics, Inflammation etc. Function: alter T1 and/or T2 and/or T2* relaxation time T1 Agents: mostly on Gd basis T1 imaging: hyperintensity T2 Agents: USPIOs (ultra small particles of iron oxide) T2 or T2*: hypointensity/hyper Other Agents: much more: Magnetization transfer etc. Mouse Tumor Gd enhanced Pre Contrast Agent Post Contrast Agent Magnevist (Gd-DTPA), ca mmol/kg, i.v. se, TR=500 ms, TE=10ms; TSE, TR=2770 ms, TE=44 ms T1 of tissue with Gd is decreased => more signal in T1 weighted sequence Non enhanced Post - Pre T2 weighted Hans Wehrl - MRI Basics PRIMA IV 25

26 Mouse Brain Mn enhanced MnCl, appx. 3µL, ca. 200 nmol, vitreous body of the eye 24 h post injection: gre3d, TR=50 ms, TE=4.2 ms, FA=65, 0.1x0.1x0.1 mm³ Mouse Brain coil Optical nerve colliculus superior Functional MRI: BOLD Why? Display functional areas in the brain during some stimulation/task Function: BOLD (blood-oxygenation-level dependent) contrast Spin Echo Gradient Echo Gradient Echo Oxy Deoxy 100% Oxygen Deoxygenated blood shows stronger signal distortion than oxygenated blood Ogawa et al. MRM 1990 normal air Hans Wehrl - MRI Basics PRIMA IV 1

27 Functional MRI: BOLD Mechanism: Stimulus: optical, electrical, mechanical, pharmacology, etc. -> increase in Neuronal activity -> Blood flow/volume -> Blood oxygenation -> MR BOLD Signal increase BOLD Signal (1%-2%) delay: appx. 8 sec after stimulus Functional MRI: BOLD But: - Signal has may contributing factors (physiological parameters, physical parameters etc.) - noisy data, signal change only 1%-2% compared to baseline - statistics needed -> activation maps superimposed on anatomy - draining veins etc. can also show activation Hans Wehrl - MRI Basics PRIMA IV 2

28 Functional MRI: BOLD It is today especially a routine tool in human studies e.g. here a finger tapping experiment MR Spectroscopy Resonance frequency of the protons is also dependent on their chemical environment e.g. protons in lipids have slightly different resonance frequency than protons in water (e.g. shielding by electrons) -> chemical shift The scale for the frequency axis is usally the ppm (parts per million) scale, to make it B 0 field independent. Higher B 0 field strengths usually also allow a better spectral resolution and discrimination. single voxels spectroscopy but also spectroscopic imaging (chemical shift imaging CSI) can be performed metabolite concentrations are then color coded. dog Selected voxel for spectroscopy Resulting 1H Proton Spectra showing different Metabolites e.g. Choline The Scale is the ppm Scale, The H 2 O Proton peak is usually not shown (appx ppm) Gruetter et al. J Magn Reson 1998 human human Hans Wehrl - MRI Basics PRIMA IV 3

29 Polarization/Hyperpolarization Equilibrium: Polarization: P= 5x10-6 for 1 H at 1.5T Hyperpolarization (-> a new MRI Technique): A non-equilibrium state where (N -N ) is increased by orders of magnitude compared to thermal equilibrium. -Hyperpolarization is independent on B 0 ( Equilibrium) -Hyperpolarization has limited lifetime Hyperpolarization Enhance the Signal of certain substances that can be used as contrast media or for metabolic pathway tracking, e.g. [ 13 C]pyruvate so far only small animals, but humans are planed (prostate cancer). Hans Wehrl - MRI Basics PRIMA IV 4

30 Hyperpolarization However some of the problems that are encountered with PET experiments are carried over to MRI Examples Mouse Brain sagital Sequence: t2_tse Coil: Mouse Brain TR: 2770 msec TE: 43.0 msec Bandwidth: 130 Hz/pix Acquisition time: 6min 48 sec Resolution: appx. 100x100 µm 2 in plane, 0.7mm slice thickness. Slices: 11 Averages: 2 Hans Wehrl - MRI Basics PRIMA IV 5

31 Examples Mouse Brain coronar. Sequence: t1_tfl_mprage Coil: Mouse Brain TR: 2770 msec, TI: 1000 msec TE: 3.0 msec Bandwidth 250 Hz/pix Acquisition time: 15min 54 sec Resolution: appx. 140x120 µm 2 in plane, 0.45 mm slice thickness. Slices: 18 (but 3D sequence) Averages: 2 Examples Mouse embryos (day 13) with 3D sequence Sequence: t2?_tse3d_iso0p22 Coil: Mouse whole body TR: 3500 msec TE: 355 msec Bandwidth 575 Hz/pix Acquisition time: 9 min 11 sec Resolution: appx. 220x220x220 µm 3 Slices: 3D sequence Averages: 2 Hans Wehrl - MRI Basics PRIMA IV 6

32 Examples Angiography Rat Brain with 3D sequence (no contrast agent) Sequence: fl_tof Coil: Rat brain TR: 14 msec TE: 8.4 msec Bandwidth 435 Hz/pix Acquisition time: 6 min 59 sec Resolution: appx. 210x170x600 µm 3 Slices: 3D sequence Averages: 2 Examples Echo Planar Imaging Rat Brain Sequence: ep2d_bold_40_120 Coil: Rat brain TR: 2000 msec TE: 18 msec Bandwidth 2895 Hz/pix Acquisition time: 2 sec for 4 slices Resolution: appx. 1.06x1.06 mm 2 in plane, 1 mm slice thickness Slices: 4 (all four slices shown in the so called Mosaic format) Averages: 1 Hans Wehrl - MRI Basics PRIMA IV 7

33 Review Magnetic field Tissue protons align with magnetic field (equilibrium state) RF pulses Relaxation processes Protons absorb Spatial encoding RF energy using magnetic (excited state) field gradients Relaxation processes Protons emit RF energy (return to equilibrium state) NMR signal detection Repeat RAW DATA MATRIX Fourier transform IMAGE Literature Magnets, Spins and Resonances (Siemens, online pdf, Basics) Magnets, Flow and Artifacts (Siemens, online pdf, Basics) functional Magnetic Resonance Imaging (S. A. Huettel et al., Sinauer, 2008, intermediate) Magnetic Resonance Imaging (E. M. Haacke et al., Wiley-Liss, 1999, advanced) (online Book, Basics) Hans Wehrl - MRI Basics PRIMA IV 8

34 Acknowledgements University of Tuebingen Claus D. Claussen Bernd Pichler Valerie Honndorf Uwe Klose Damaris Kukuk Petros Martirosian Fritz Schick Stefan Wiehr MPI for Biological Cybernetics, Tuebingen Rolf Pohmann ETH Zurich Markus Rudin DFG PI 771/1-1 NIH Grant EB Wilhelm Schuler-Foundation Hans Wehrl - MRI Basics PRIMA IV 9