YR1 Lecture 1H - MRI Basics 2022 PDF

1 Introduction to Magnetic Resonance Imaging (MRI) MRI Magnet Videos MRI magnets are extremely strong. This video is only a 4 tesla magnet. The strongest research MRI at WSU (Bldg 17) has a 14.1 tesla magnet. https://www.youtube.com/watch?v=6BBx8BwLhqg Prof. William S. Price Nanoscale Group School o...

1 Introduction to Magnetic Resonance Imaging (MRI) MRI Magnet Videos MRI magnets are extremely strong. This video is only a 4 tesla magnet. The strongest research MRI at WSU (Bldg 17) has a 14.1 tesla magnet. https://www.youtube.com/watch?v=6BBx8BwLhqg Prof. William S. Price Nanoscale Group School of Science Western Sydney University, Australia Quenching a superconducting magnet. This is rare and is normally planned: https://www.youtube.com/watch?v=tPqduF5xB-o To maintain the superconducting state of the magnet the solenoid is in liquid helium. In a quench the liquid helium becomes a gas. If the air in the room was displaced by the helium people could be asphyxiated. www.westernsydney.edu.au/nanoscale [email protected] Director of WSU node of the National Imaging Facility MR safety test: https://www.youtube.com/watch?v=MMP8gt4nZ6I 2 MRI Learning Outcomes Have you had an MRI? Were you frightened? Explain the fundamental physical principles behind MRI. How is position sensed in MRI? A patient might ask you: How does MRI work? Is it dangerous? Why am I being placed in an enormous magnet? Why are you sending me for an MRI and not a CT? Does it involve radioactivity? Why does the MRI show my brain tissues as grey/white/black? o Why is it so noisy? o o o o o o Explain the origins of the information content in MRI. What is the source of contrast in an MRI? Could you answer and reassure a patient? (if you cannot answer the patient might have little faith in you) 1.5 tesla MRI Be aware of artifacts in MRI. Why is it such an important tool in medical research? 3 4 NMR, MRI and Nomenclature MRI of the Heart NMR = Nuclear Magnetic Resonance MRI = Magnetic Resonance Imaging MRI is just one area of NMR. MRI is the observation of a spatial variation in an NMR observable. NMR MRI The ‘nuclear’ in NMR has nothing to do with nuclear reactors or biologically damaging radiation coming from radioactive materials. In NMR, we are looking at the magnetic properties of atomic nuclei. Nevertheless, ‘Nuclear’ is normally omitted and so we have: Magnetic Resonance Imaging (MRI) and not Nuclear Magnetic Resonance Imaging. 5 6 1 1 Why should we be interested? Simple Spin Physics NMR (and thus MRI) provides information otherwise unobtainable. The next few slides will explain why MRI needs a magnet. It (generally) does not require labelled probe molecules. Most elements have at least one NMR sensitive isotope including those that are biologically important (e.g., 1H, 7Li, 13C, 23Na, 31P…). But the sensitivity of each isotope is different. It is non-invasive and does not require high energy radiation. So no damage to DNA. Without physically spinning, such nuclei possess an intrinsic (quantum mechanical) angular momentum called ‘spin’, as well as a magnetic moment. They can be thought of as a magnetic dipole and, thus, behave something like a microscopic bar magnet. Unique sources of contrast (esp. those involving molecular motion). Excellent soft tissue contrast (cf. X-rays and CT). It is becoming more and more important in medicine. 7 8 Natural Abundance and Sensitivity Nucleus Natural Abundance % 99.98 1H (protons) 2H (deuterium) 0.02 3H (tritium) 13C Angular Momentum Videos Absolute sensitivity 1 https://www.youtube.com/watch?v=8H98BgRzpOM https://www.youtube.com/watch?v=vqHXFKJddfM https://www.youtube.com/watch?v=h2k4TRomUB8 1.45  10-6 0 0 1.1 1.76  10-4 The overall sensitivity of a nucleus depends on the natural abundance of the nucleus and its inherent sensitivity. Obtaining sufficient signal is a problem and this is why at present, clinical MRI is performed only with 1H. To perform MRI with isotopes with low abundance (e.g., 13C), you need isotopically labelled samples (e.g., 13C-labelled glucose). Other nuclei (e.g., 19F, 31P) will become more important as MRI technology improves. 9 10 Effects of an External Magnetic Field Simple Spin Physics If we apply a magnetic field, B0 (unit = tesla (T), or gauss: 1 gauss = 0.0001 tesla), the situation changes dramatically for two reasons: (i) alignment and (ii) precession. In MRI, we are always concerned with an ensemble (i.e., an enormous number) of such spins. First, in a statistical sense, the spins align with the magnetic field. Note the alignment takes time to occur (related to spin relaxation – discussed later). For example, 18 mL of water (~1 mole) contains 2 moles of 1H (12.044 × 1023 protons). In the absence of a magnetic field their orientation is random. Vector Sum + =0 B0 z Vector Sum A group of such randomly oriented nuclei has zero net (i.e., vector sum) magnetisation. y x M0 Laboratory Frame Static Magnetic Field 11 NB a magnetic field is a vector quantity. Net nuclear magnetisation at thermal equilibrium (hence the 0) (VERY small) M0 increases as the static field B0 increases. 12 2 1 Spin Precession in a Magnetic Field Precession (or Resonance) Frequency (rad s-1) (note: 1 Hz = 2  rad s-1) (Depends on the nucleus e.g.,1H, 13C, 23Na)    B0 Larmor equation: So What Do We Detect? A simple generator Gyromagnetic Ratio (rad s-1 T-1) As on a bicycle Static Magnetic Field (T) Rotating the magnet with respect to the coil (or vice versa) will generate a voltage which oscillates at the speed of rotation of the magnet.  In magnetic resonance the magnet is in the nucleus. B0 In NMR, the net nuclear spin magnetisation (M0) plays the role of the magnet and we place a coil around the spins to detect the oscillating voltage (at the Larmor frequency ). This is the origin of the NMR signal from which we ultimately get the MRI image. Precession like a child’s spinning top. The spins precess faster as the magnetic field increases. NB the nuclei do not spin. The spins DO NOT emit radiowaves – we are detecting rotating magnetisation. Protons in the Earth’s magnetic field (B0 50 T ), ( H) = 2.67 × 10 rad s T   2 kHz. 1 8 -1 -1 13 A simple generator  If B0 is increased then M0 and, thus the acquired signal. will be stronger. This is why we need STRONG magnets. Precession (‘Resonance’) Frequencies and Magnetic Fields So What Do We Detect? Rotating the magnet with respect to the coil (or vice versa) will generate a voltage which oscillates at the speed of rotation of the magnet. As on a bicycle In NMR, the net nuclear spin magnetisation (M0) plays the role of the magnet and we place a coil around the spins to detect the oscillating voltage (at the Larmor frequency ). This is the origin of the NMR signal from which we ultimately get the MRI image. NB The spins do NOT emit radiowaves – we are merely detecting the rotating net spin magnetisation. 15 Biomedical Magnetic Resonance Facility (BMRF) (Bldg 17 Campbelltown Campus) 500 MHz (11.7 T) 300 MHz (7.0 T) 600 MHz (14.1 T) B0 Nucleus 2.35 T 9.4 T 21.1 T 1H 100 MHz 400 MHz 900 MHz 13C 25.2 MHz 100.6 MHz 3H 106.7 MHz 426.7 MHz 960 MHz 197Au 1.72 MHz 15.4 MHz 6.85 MHz 226.3 MHz NB, these are in the realm of radio frequencies (rf). This is why we refer to the coil around the sample using for perturbing the spins and receiving the signal as the “rf coil”. The stronger the magnetic field the greater the sensitivity. The Earth’s magnetic field is ~ 50 T (1H frequency ~ 2 kHz). Most clinical whole body MRI scanners are based on 1.5 or 3 T magnets. If the signal is weak, we increase B0 then M0 and thus the acquired signal will be stronger. We need STRONG magnets. 400 MHz (9.4 T) 14 Normally superconducting magnets are used. Providing the magnet is kept at extremely low temperatures, the magnet is effectively permanent. Such magnets cannot simply be switched off and on again. So even if the MRI is not in use, the magnet is ON. 16 What not to do with an MRI Magnet NB, the strength of an MRI is referred to either by the field strength of the main magnet in tesla or by the 1H resonance frequency. Compare to the table on the previous page. 3.0 T Magnet (128 MHz) NB: The magnet is ALWAYS on! Even if the machine is turned off. What are the red circles? Why does the room have an oxygen sensor? 17 Safety is always an issue with NMR/MRI (see www.youtube.com/watch?v=6BBx8BwLhqg). If a superconducting magnet quenches an enormous amount of gas is produced and one could asphyxiate (see www.youtube.com/watch?v=9SOUJP5dFEg). Hence such facilities have an oxygen sensor. 18 3 1 RF Coils and Filling Factors 11.7 T MRI Study of Preeclampsia The signal-to-noise is better when the rf coil is just big enough (i.e., a high filling factor). Being held tight also reduces motional artifacts. MRI probe body and coil for a research MRI Head coil 19 The Music you get Depends on the Musical Score Bobek, G., Stait-Gardner, T., Surmon, L., Makris, A., Lind, J.M., Price, W.S. and Hennessy, A. (2013) Magnetic Resonance Imaging Detects Placental Hypoxia and Acidosis in Mouse Models of Perturbed Pregnancies. PLoS ONE 8(3):e59971 1-6. 20 An Example of a Diffusion-MRI Pulse Sequence Diffusion MRI sequence Orchestral Score MUSIC NMR/MRI Orchestral score ↔ Pulse sequence Conductor ↔ Computer Musical instruments ↔ rf pulses, magnetic gradient pulses, delays Audience ↔ Noise Music ↔ Information/Spectra/Image properties Diffusion‐measuring gradient pulses 21 In reality there are thousands of pulse sequences and it is a huge area of research. Different pulse sequences provide different information 22 From the Signal to the Spectrum (or Image) An NMR/MRI Experiment Pulse Sequence Fourier Transform (thermal equilibrium perturb acquire signal)repeat Signal spectrum/image FID The Pulse Sequence encodes various NMR observables into the signal. Spatial differences in the NMR observables provide the contrast. There are 100s of sequences. The perturb step will always include radio frequency (rf) electromagnetic pulse(s) to excite (add energy to) the spins, and may also include spatially modulated applied magnetic fields, and delays. It depends on what information you want. This step is referred to as the NMR or MRI ‘sequence’. An analogy is the musical score to an orchestra. Only extremely small energies are involved! The signal is sometimes called the free induction decay (FID). We generally have to sum the results of a number of scans as the signal is weak. After the rf excitation, the spin system tries to regain thermal equilibrium through the process of spin relaxation. Fourier Transformation Spectrum See later Time Domain Signal versus time 23 Frequency Domain frequency versus intensity Recall the analogy with sounds with a middle C tuning fork 261 Hz. The Fourier Transform takes us from the time domain signal (i.e., FID) to the frequency domain (i.e., the spectrum). The inverse Fourier Transform would go in the other direction. Can give frequency in radians per second, hertz or parts per million (ppm) of the spectrometer frequency. In reality there are non-ideal effects. 24 4 1 Sources of Information NMR Phenomena Information Provided Effect Type of molecule, Environment, Motion and Position provide distinct signatures observed as changes in frequency and amplitude in NMR signals. Chemical Shift Spin Relaxation → local environment 1. Spin-Lattice → (mainly) reorientational motion 2. Spin-Spin → (mainly) reorientational motion Spatial and/or motional encoding Magnetic gradient → An NMR/MRI experiment involves some combination of these factors. Ultimately these magnetic resonance observables give the contrast in MRI. 26 Chemical Shift 1H Local electronic distributions affect the resonance frequency since the electron shells shield the nucleus from B0. different resonance frequencies B0 Chemical Shift W ater:E th an o l 50:50 a t 298 K electron shells M e th yl CH3CH2OH ↔ H2O M eth y len e Chemical shift effects are extremely small – in parts per million (ppm) of the base resonance frequency (0). For example, for a 400 MHz spectrometer 1 ppm = 400 Hz. W ate r H y d ro xy l 1 H Chemical Shifts 5.5 5.0 4.5 4.0 3.5 3.0 3.0 2.5 22.0.0 1.5 1.0 (ppm) Thus the very small differences in resonance frequency give chemical information. 27 This is the spectral width – the ‘observation window’, the analogous parameter when acquiring an image is the Field of View (FOV). 28 Types of Molecular Motion 1H Spectrum of Blood Plasma Time taken to reorientate by ~ 1 radian Translational (self-) Diffusion, D (m2s-1) Reorientational Correlation Time, c (s) Different parts of molecule may have different reorientational motions, but a single diffusion coefficient characterises the whole molecule. Lysozyme W.S. Price, W.-C. Perng, W.-M. Kwok, L.-P. Hwang, Applications of High Field NMR Spectroscopy to Clinical Medicine, Chinese J. Magn. Reson. (1993) 10, 453-476. NB Molecules in different tissues may have different motional properties 29 30 5 1 NMR Relaxation Spin-Lattice Relaxation Relaxation depends on fluctuating magnetic fields which result from (mainly) reorientational motion. B0 B0  M0 1. Spin-lattice (or Longitudinal) Relaxation Deals with the relaxation of the spin system back to thermal equilibrium. ‘NMR’ energies are very small and relaxation does not really affect the lattice. Often characterized by a time constant T1. perturbation spin-lattice relaxation thermal equilibrium 2. Spin-spin (or Transverse) Relaxation Deals with the loss of phase coherence of a group of spins. Often characterized by a time constant T2. The rf excitation (perturbation) increases the precession angle away from B0. At the end of the perturbation, the spin magnetisation returns to its thermal equilibrium value (M0) through spin-lattice relaxation. This process is often described by an exponential with a time constant T1. It involves a loss of energy from the perturbed spin-system to the surroundings (e.g., the ‘lattice’). 31 32 Three Types of Translational Motion Spin-Spin Relaxation e.g., water Consider two initially coherent spins Corresponds to large net magnetisation As time passes the spins become incoherent e.g., water e.g., ink in water Corresponds to smaller and ultimately nil net magnetisation coherent The loss of coherence is generally an exponential process described by a time constant T2. Different dependence on reorientational rate than spin-lattice relaxation. Involves a loss of order not energy. 33 How to Encode Position? incoherent incoherent Willis et al., Diffusion: Definition, Description and Measurement, in: J. Fisher (Ed.) Modern NMR Techniques for Synthetic Chemistry, CRC Press, 2014, pp. 125-175. Key point: NMR/MRI can measure all of these. In MRI “diffusion” normally refers to self-diffusion. 34 Position and Frequency Using spatially well-defined magnetic field gradients to spatially encode NMR data. MRI could not exist without this. Question: Even without seeing the pianist’s hands, how can you guess where they are? 36 6 1 Magnetisation Helix Position and Frequency (2) If the magnetic field changes with position, then position will be encoded in the resonance frequency. Below the gradient is along the z axis.   z    B0  static field contribution  Gz z magnetic gradient contribution Slower Precession The resonance frequency is a linear function of position along the direction of the gradient.   z  z Faster Precession Answer: we have a relationship between position and frequency. Specifically we have a frequency gradient along the direction of the keyboard. 37 38 No Gradients No Image Magnetisation Helix Use G if the gradient pulse is being used for spatial location. Use g if the gradient pulse is used for probing motion. rf pulse k and q are defined identically: they are both the area of the gradient pulse multiplied by . Use k for spatial location, use q if you are probing motion. π/2 /2 z 1H NMR signal from the water in the cylinders. Water k (=q) are the pitch of the helix. 1D Spectrum Lorentzian Lineshape rf Chemical Shift Plastic plug in an NMR tube A simple pulse sequence The spectrum is the sum of both cylinders of water Pitch Gupta, Stait-Gardner and Price Adsorption (2021) 27, 503-533. 39 40 One-Dimensional Imaging Due to presence of the magnetic gradient, Gz,  now depends on the position along the z axis. π/2 /2 Now the signal is a sum of two Gz z 1D Imaging The image is a one dimensional projection of the sample onto the z-axis (i.e., the direction of the gradient). An analogy is a shadow. Water Plastic plug in an NMR tube frequencies 1D Image rf Gz Acquire signal in the presence of a magnetic gradient z (Not chemical shift) The contribution of each cylinder is now separated Extending this idea to three dimensions allows the means to acquire three dimensional images. Gupta, Stait-Gardner and Price Adsorption (2021) 27, 503-533. 41 42 7 1 Voxels, Pixels and Resolution Audible Noise and the Imaging Procedure A pixel (‘picture element’) is the smallest unit of a display (e.g., TV screen). A voxel (‘volume element’) is the three-dimensional analog of a pixel. An imaging procedure will involve many rf and magnetic gradient pulses. The rf pulses are extremely short (10s of s) but the gradient pulses are on the order of 10s of ms. The rf pulses are silent but the gradient pulses make a lot of audible noise. In clinical MRI voxels are typically (1 mm)3. Resolutions in high resolution MRI (aka ‘NMR Microscopy’) approach (10 m)3. 43 44 The Imaging Process Medical MRI, Contrast and Artifacts The density of nuclei at position r (i.e., “r-space”) The signal containing the effects of contrast in “gradient” or kspace” The density of nuclei at position r (i.e., “r-space”) We can combine MRI with NMR sources of contrast to discriminate between different regions of tissue. But we must be careful of artifacts. Gupta, Stait-Gardner and Price Adsorption (2021) 27, 503-533. 46 Sources of Contrast An MRI Image Chemical shift Relaxation Temperature (as it will affect motion which will affect relaxation) Diffusion Flow Any NMR observable with a spatial dependence The colour is completely artificial. Notice the uneven colouration? This is an artifact. One pass through a typical imaging sequence takes on the order of 10 ms, what happens if there is motion during the sequence? 1 cm Covering the whole sample and including signal averaging the total time may be of the order of 30 minutes. A very high resolution MRI of a Calamondin 47  For example, water in a tumour might diffuse differently than water in normal tissue. A Diffusion-MRI pulse sequence is sensitive to diffusion and thus would allow discrimination between tumour/nontumour. 48 8 1 Common Medical Imaging Pulse Sequences In vivo 1H NMR Spectrum at 4.7 T The different chemical environment (i.e., whether the H atom is in water or in fat) causes very small change in resonance frequency. T1-weighted T2-weighted Diffusion Filter Fat suppressed Contrast – introduce a contrast agent (e.g., a gadolinium Kaldoudi and Williams, Conc. Magn. Reson. (1993) 4, 53. complex) which changes relaxation properties of a specific tissue. Angiography In conducting an image of this sample you may wish to differentiate between the water and fat. 49 1H 50 Motional Contrast Images of a Live Cockroach at 4.7 T Four different MRI images of the same brain – each with different contrast (A, B, and C all involve translational motion). Conventional image (‘density’ image; that is the ‘density’ of 1H) q-space displacement q-space probability Water-only image Fat-only image Diffusion anisotropy Kaldoudi and Williams, Conc. Magn. Reson. (1993) 4, 53. Relaxation-weighted Cohen and Assaf, NMR in Biomedicine (2002) 15, 546. 51 Postembryonic Development of Sarcophaga Peregrina (flesh fly) 52 Artifacts Since during the imaging pulse sequence the precession frequency is correlated with position, if there is a local distortion of the magnetic field some part of the sample will appear to be in the wrong place (see previous slide). An analogy would be a mistuned piano. A movie made from 138 images that were acquired at ~ 1 hour intervals. The next two slides demonstrate the basis of an MRI artifact that arises because the MRI acquisition parameters were improperly set. There are numerous other sources of artifacts. The bright ‘arrowhead’ features are artefacts resulting from local distortion of the magnetic field due to the change in magnetic susceptibility at the gas/tissue interface. 12 mm 53 54 9 1 Aliasing in MRI Aliasing Field of View Example from NMR Brain MRI with FOV = 24 18 cm Full spectrum Insufficient spectral width Brain MRI with FOV = 24  24 cm Even more limited SW Torres AM, Price WS. Common problems and artifacts encountered in solution-state NMR experiments. Concepts Magn. Reson, A. 2017: 45, e21387. 55 Krupa K, Bekiesinska-Figatowska M. Artifacts in magnetic resonance imaging. Pol. J. Radiol. (2015) 80: 93-106. 56 10