January 15 th : Presentation of tasks (08:30 11:45) Fascinating applications in MR (cont.)

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1 MR Radiology Lab Ruomin Hu, M.Sc. Computerunterstützte Klinische Medizin Medizinische Fakultät Mannheim Universität Heidelberg Theodor-Kutzer-Ufer Mannheim Organization January 8 th : Review of the basics (08:30 11:45) Fascinating applications in MR January 15 th : Presentation of tasks (08:30 11:45) Fascinating applications in MR (cont.) January 29 th : MR experiments will be performed in 2 groups (14:30 17:45) T1, T2, TOF, DTI 1 st group 14:30 (Meet in the MR patient waiting area Haus 3 Level 1) 2 nd group 16:00 Group 1: Muntoha, Yao, Pais, Iporre, Yang, Li, Nagappan Group 2: Fok, Xiao, Dalkilic, Aung, Vigo, Eskandarian, Naqvi Valid for both Jan. 15th and 29th. Ruomin Hu I Slide 2 I

2 Exercise: Measurement of T1 (Group 1) 1. Calculate the T1 values from an inversion recovery measurement in white matter (WM), grey matter (GM) and cerebralspinal fluid (CSF) Experiment #1: 6 images were measured (IR_01.ima... IR_06.ima, data at: Medical Physics: Lab Rotation MR-Radiology ) with TI = 50, 400, 550, 750, 1200, 2000 ms. Plot signal intensity (= mean value of ROI) as a function of TI and calculate T1 via fit a*(1-b*exp(-x/c)) Ruomin Hu I Slide 3 I Exercise: Measurement of T2 (Group 2) 2. Calculate the T 2 values from a spin echo measurement in white matter (WM), grey matter (GM) and cerebralspinal fluid (CSF) Experiment #2: 11 images were measured (SE_01.ima...SE_11.ima, data at: Medical Physics: Lab Rotation MR-Radiology ) with TE = 25, 50, 75,..., 275 ms. Plot signal intensity (= mean value of ROI) as a function of TE and calculate T2 via fit a*exp(-x/b) Ruomin Hu I Slide 4 I

3 Fascinating applications in MR Review of the basics Exercises Everybody should have a copy of the presentation (whether done in group or alone) One person from each group will be chosen randomly That person will give a presentation of 10 min on 1. Background 2. How you solved the task step by step. 3. Results of T1 or T2 have to be obtained by fitting. 4. Do not just take screenshots of your code! Explain. 5. Do your results match literature values? Ruomin Hu I Slide 5 I Familiar with basics of MR applications? (Jan 8th 2018) (Jan 15th 2018) I studied it for the exam Physics behind MR From relaxation to contrast Standard sequences MR just got even more interesting! MR angriography Diffusion Non- 1 H MR imaging Hardware (Matthias Malzacher) Spectroscopy Safety aspects Performing a scan MR elastography (Wiebke Neumann) Peripheral nerve stimulation (Mathias Davids) Quantitative susceptibility mapping (Simon Hubertus) Perfusion (Tanja Uhrig) Ruomin Hu I Slide 6 I

4 Chapter 1 Brief Review Ruomin Hu I Slide 7 I Where did the N NMR go? 1940s: nuclear induction 1950s: nuclear paramagnetic resonance 1950s: nuclear magnetic resonance (NMR) 1980s: NMR imaging currently: MR imaging nuclear? Ruomin Hu I Slide 8 I

5 Splitting of energy levels: Zeeman effect Spin = 1/2 Spin = 3/2 m = -1/2 m = +1/2 B = 0 B = B 0 B = 0 B = B 0 Ruomin Hu I Slide 9 I Splitting of energy levels: Zeeman effect m = -1/2 M 0 B 0 ΔE = ħ ω 0 = ħ γ B 0 m = +1/2 Larmorfrequency RF pulse change of energy levels Curie s law: ω 0 = γ B 0 ω 0 : Larmorfrequency γ: Gyromagnetic ratio ΔE = ħ ω 0 = ħ γ B 0 E RF = ħ ω RF ħ: Planck constant ρ 0 : number of nuclei k: Boltzmann constant Ruomin Hu I Slide 10 I

6 Quantum mechanics classical mechanics quantum mechanics Schrödinger equation: classical mechanics Slichter, Principles of Magnetic Resonance, 1978 dm ( t) dt M B Bloch equation Ruomin Hu I Slide 11 I and pulses 90 -pulse ( /2-pulse) N -1/2 = N +1/2 M z = 0 to : spins / 1 mm 3 at 1.5 T 180 -pulse ( -pulse) N -1/2 > N +1/2 M z = -M 0 to : spins / 1 mm 3 at 1.5 T source: Lissner and Seiderer. Klinische Kernspintomographie 1987 Ruomin Hu I Slide 12 I

7 Faraday induction A Faraday s law of induction dφ t U ind = dt Magnetic flux φ(t) = B(t) A = φ(t) t Time-dependent B-field B t = B 0 cos ωt When is U ind 0? 1. φ(t) = 0, if B(t) A (perpendicular), or B t = 0 (no B field), or A = 0 (no coil) 2. U ind = 0, if φ(t) = 0 (no magnetic flux) φ(t)/ t = 0 (no change in φ per time unit) 3. " ": induced reaction against source of action z x A y Ruomin Hu I Slide 13 I Faraday induction Faraday s law of induction dφ t U ind = dt = φ(t) t coil with rotating magnet equivalent coil with rotating magnetic moments z Magnetic flux N S φ(t) = B(t) A M y y x Time-dependent B-field B t = B 0 cos ωt Ruomin Hu I Slide 14 I

8 Quiz: FID glas wall open to street level opening, where phantom goes in shielded by metal housing observed when measuring 23 Na signal at 105 MHz not observed when measuring any other nucleus (e.g. 1 H at 400 MHz, 35 Cl at 39 MHz) observed: expected: What are these non-random, non-noise oscillations? Ruomin Hu I Slide 15 I Match RF coil to purpose of examination Coil Characteristics: Transmit and receive with the same coil Transmit and receive with different coils Birdcage Helmholtz Surface (flat, bent, array...) Resonant to one nucleus Double/triple-resonant to multiple nuclei Number of transmit and receive channels double-resonant 1 H/ 23 Na birdcage head coil used at Siemens Trio 3 T 1 H array body coil used at Siemens Skyra 3 T Scanner model Courtesy: Siemens Healthineers Region of interest (head, knee ) 23 Na bent surface animal head coil used at Bruker BioSpec 9.4 T Ruomin Hu I Slide 16 I

9 MRI components: physical parameters gradient shim transmitter receiver technical component physical parameter Static field B 0 M 0 RF pulse Signal control panel computer 350 MHz Gradients G xyz Image 350 MHz image processor Ruomin Hu I Slide 17 I Chapter 2 Relaxation Ruomin Hu I Slide 18 I

10 Bloch equations Bloch equation after 90 -pulse in laboratory frame of reference: M = M x M y M z M z t = M 0 1 e t T1 M x t = M 0 e t T2 sin ωt M y t = M 0 e t T2 cos ωt laboratory frame of reference rotating frame of reference rotating frame of reference: M z t = M 0 1 e t T1 M xy t = M 0 e t T2 Ruomin Hu I Slide 19 I Classical explanation of T1 & T2 T1 longitudinal relaxation: energy transfer from spin to the environment T2 transverse relaxation: loss of phase coherence with other spins T2 T T2 relaxation effect 1: loss of coherence due to T1 relaxation spin left M xy -plane 2. T2 relaxation effect 2: loss of coherence due to local static magnetic field B loc new Larmor frequency ω = γ B 0 + B loc phase difference accumulation φ = γb loc t T1 and T2 are of intrinsically different physical nature ( independent ), but T1 relaxation inevitably leads to T2 relaxation! Ruomin Hu I Slide 20 I

11 Why no spontaneous RF emission? universal tendency to occupy the energetically most favorable state example: laser NMR however: photon (RF wave) emission stimulation (excitation) photon emission RF excitation T1, T2 relaxation Einstein: probability of spontaneous emission ~f 3 highly probable for visible part of the spectrum with f Hz highly improbable for radiofrequency part of the spectrum f 10 8 Hz Energy emission in NMR are induced through direct interactions with external environment. Ruomin Hu I Slide 21 I Important types of interaction 1. dipole-dipole interaction dominant relaxation mechanism for dipole nuclei nuclei with spherical charge distribution dipole moment ( two poles ) phenomenological explaination physics, quantum mechanics interaction of dipole nuclei with the magnetic field gradient of another dipole 2. electric-quadrupole coupling dominant relaxation mech. for quadrupole nuclei nuclei with non-spherical charge distribution quadrupole moment ( four poles ) 3. chemical shift basis for MR spectroscopy e - clouds depend on electronnegativity of the local molecular environment different shielding by e - clouds from B 0 experienced by nuclei in different locations interaction of quadrupole nuclei with the electric field gradients of the surrounding electron clouds Ruomin Hu I Slide 22 I

12 Dipole-dipole interaction dominant relaxation mechanism for dipole nuclei nuclei with spherical charge distribution dipole moment ( two poles ) interaction of dipole nuclei with the magnetic field gradient of another dipole (nucleus or electron) Strength of dipole-dipole interaction depends on 1. type of particles γ electron γ proton dipole-dipole interaction between a nucleus and an electron much stronger! contrast agent with unpaired electrons induces relaxation and reduces relaxation time 2. distance ~1/r 6 short-range intramolecular interaction stronger than long-strange intermolecular interaction 3. angle ~ 3 cos θ relative motion If a spin tumbles (=rotates) with ω, its dipole field also tumbles with ω. If ω ω 0, local fluctuating field B loc induces T1 relaxation (energy transfer) If ω 0, static field B loc induces T2 relaxation (dephasing) Ruomin Hu I Slide 23 I Local fluctuating magnetic field B loc (t) In a real spin system (tissue) every nucleus is surrounded by intra- and intermolecular magnetic moments Thermal motion (random molecular tumbling) of the surrounding magnetic moments leads to an additional local fluctuating magnetic field B loc t with typical spectral distribution J(ω) Spectral distribution J(ω 1 ) describes the probability of finding fluctuations of nearby magnetic moments that have the frequency ω 1. Different surroundings cause different J(ω) Area under J ω = 1 J ω 0 for soft tissue ω = 0 spectral distribution J ω slow fluctuations soft tissue fast fluctuations ω = ω 0 Ruomin Hu I Slide 24 I

13 Physical model of relaxation T2, J(0) static dephase T1, J(ω 0 ) Larmor energy transfer spectral distribution J ω slow fluctuations J ω 0 for soft tissue soft tissue fast fluctuations fluctuation slow medium fast slow medium fast probability high medium low low high low rel. time small medium large large small large rel. rate fast medium slow slow fast slow ω = 0 ω = ω 0 1. T1: components of J(ω) at 0 allow / stimulate energy transfer from the spin system to the lattice 2. T2: mainly static frequency components J(ω) of B loc t at ω = 0 contribute to coherence loss no energy transfer from the spin system Ruomin Hu I Slide 25 I Examples: in vivo relaxation times tissue T 2 [ms] T 1 [ms] at 0.5 T T 1 [ms] at 1.0 T T 1 [ms] at 1.5 T cerebralspinal fluid grey matter white matter skeletal muscle myocardium liver kidney spleen fat blood proteins tendon ice B 0 -dependency of T1 and T2? 2. Characteristics of organs? 3. Characteristics of solids/large molecules? 4. Characteristics of watery media? 5. T1 or T2-weighting to distinguish CSF/brain? 6. Relate to relaxation vs. tumbling rate graph Bottomley et al. Med Phys 1984 Haacke et al Ruomin Hu I Slide 26 I

14 Chapter 3 Standard Sequences Ruomin Hu I Slide 27 I How to rephase? 180 refocusing pulse echo t TE too slow too fast too fast too slow Ruomin Hu I Slide 28 I

15 What do spin echo sequences eliminate? RF excitation M XY signal 1/T2* = 1/T2 + 1/T2 T 2 * effective relaxation with T 2 * < T 2 T 2 true relaxation due to irreversible dephasing T 2 scanner relaxation due to static field inhomogeneities T2 = intrinsic property of tissue T2* = contains irrelevant information SE eliminates relaxation effects by static field inhomogeneities to reveal true T2 Ruomin Hu I Slide 29 I Dössel. Bildgebende Verfahren in der Medizin 2000 T2 contrast Two tissues with different T2 relaxation times very short TE no contrast medium TE high contrast very long TE no signal M xy 10 ms 100 ms 1000 ms TE Ruomin Hu I Slide 30 I

16 Inversion Recovery Sequence 180 -pulse inverts M 0 to M 0 on the z-axis M z starts to recover to thermal equilibrium with T1 after TI 90 -pulse moves M z to the xy-plane FID decays with T2 * repeat with different TI T 1 determination selective tissue suppression Ruomin Hu I Slide 31 I T1 contrast Two tissues with different T1 relaxation times very short TI no contrast medium TI selective suppression very long TI no contrast M z WM GM TI 10 ms 400 ms 600 ms 6000 ms Ruomin Hu I Slide 32 I

17 How to deduct TE/TR for the desired contrast? proton density: S~ρ 1 e TR T1 e TE T2 e x 1 e TR T1 1 TR e TE T2 1 TE 0 poor contrast: 1 e TR T1 0 TR 0 e TE T2 0 TE T1 contrast: 1 e TR T1 1 TR e TE T2 1 TE 0 T2 contrast: 1 e TR T1 1 TR e TE T2 1 TE 0 Ruomin Hu I Slide 33 I Gradient echo sequence SE: uses 180 to focus FID T2-decay GRE: uses gradients to dephase and rephase, FID T2*-decay no 180 pulses: less concern with SAR, echoes recorded much faster short TE FLASH: small α, short TR short TE & short TR GRE = basis for rapid imaging techniques M z a M xy example: a = 20 M z - reduction by 6% M xy - value 34% of M z Ruomin Hu I Slide 34 I

18 Fast gradient echo imaging: EPI echo-planar imaging EPI multi-gradient imaging technique single-shot technique high gradient requirements strong T 2 * dependence susceptibility artifacts fastest imaging technique Ruomin Hu I Slide 35 I Fast gradient echo imaging: EPI Ruomin Hu I Slide 36 I

19 Chapter 4 MR Angiography Ruomin Hu I Slide 37 I Observe blood flow with MR angiography (MRA) Blood MR signal intensity affected by 1. Technical factors Type of pulse sequence TR, TE, α Slice thickness / gap Flow compensation, gating 2. Physical characteristics Type of flow: laminar, turbulent Velocity, acceleration, direction Ruomin Hu I Slide 38 I

20 Dark blood and bright blood MRA MRA Techniques Dark Blood no pulsation artifacts cardiac imaging vessel wall disease difficult to separate from low-signal structures dark blood Bright Blood head, abdomen and extremities "time-of-flight" oldest and most popular MRA without contrast agent time-of-flight TOF bright blood Ruomin Hu I Slide 39 I Time-of-Flight (TOF): flow-related enhancement Time-of-flight effects = signal variations resulting from the motion of protons flowing into and out of an imaging volume during a given pulse sequence. Question: How to use TOF effects to do MRA? TR >> T1 satisfied M z recovers to M 0 before next RF pulse TR >> T1 not satisfied M z does not recover to M 0 before next RF pulse Partially saturated Steady-state signal M SS < M 0 Ruomin Hu I Slide 40 I

21 Time-of-Flight (TOF): flow-related enhancement a. Stationary tissues partially saturated low steady-state signal appears dark b. Inflowing blood not partially saturated high magnetization M 0 appears bright Postprocessing: maximum intensity projection creates MR angiogram Ruomin Hu I Slide 41 I Chapter 5 X-Nuclei Imaging Ruomin Hu I Slide 42 I

22 X-nuclei used in in vivo measurements spin ½ nuclei ( dipolar nuclei ) spin > ½ nuclei ( quadrupolar nuclei ) depends on isotope Z=1 H 1 H (99.98%) 2 H (0.02%) 3 H (0%) spin ½ spin 1 spin ½ 16 O (99.8%) 17 O (0.038%) 18 O (0.2%) spin 0 spin 5/2 Spin 0 Z=2 He Z=11 Li Z=6 C Z=7 N Z=8 O Z=9 F Z=11 Na Z=12 Mg Z=15 P Z=17 Cl Z=19 K Z=54 Xe slide design courtesy Nagel, DK-ISMRM 2017 Ruomin Hu I Slide 43 I O: Cerebral metabolic rate of oxygen consumption oxygen / glucose metabolism C output H 2 17 O water (metabolic water) 15 O PET (radioactive) input 17 O-labeled oxygen inhalation experiments quantitative, non-invase mapping of cerebral metabolic rate of oxygen consumption methods e.g. 3D CSI, UTE Zhu & Chen, Progress in Nuclear Magnetic Resonance Spectroscopy 59 (2011) Ruomin Hu I Slide 44 I

23 23 Na, 35 Cl, 39 K linked by cell metabolism Na + : most abundant cation in vivo Cl-: most abundant anion in vivo [Cl - ] = 110 mm Cl - Cl - closely linked protein functionality dependent on type of disease progression of disease all spin 3/2 nuclei Cl - Cl - Cl - 23 Na most abundant naturally occuring X-nucleus in vivo [Cl - ] = 10 mm Cl - 23 Na MRI most commonly studied X-nucleus MRI Cl - channel Cl - Adapted from Madelin & Regatte JMRI 2013;38: Ruomin Hu I Slide 45 I Na: Tissue sodium concentration (TSC) Areas of application: whole body brain abdomen cartilage muscle kidney breast whole body glioblastoma (IV) T1 T1+contrast T2 multiple sclerosis proton den. T1 DWI Na Na+fluid supp Na Na TSC Nagel et al. Invest Radiol 2011;46: Inglese et al. Brain 2010;133: Wetterling et al. Phys Med Biol 2012;57: Ruomin Hu I Slide 46 I

24 Multinuclear NMR MRI 7 Li 3 He Hyperpolarization 17 O 23 Na 129 Xe 35 Cl 39 K 1 H 19 F 13 C 31 P MRS/MRSI slide design courtesy Nagel, DK-ISMRM 2017 Ruomin Hu I Slide 47 I Multinuclear NMR 7 Li 3 He spin ½ nulcei 17 O 23 Na 129 Xe 35 Cl 39 K quadrupolar nuclei spin > ½ ( fast relaxing ) 1 H 19 F 13 C 31 P slide design courtesy Nagel, DK-ISMRM 2017 Ruomin Hu I Slide 48 I

25 Why is X-nuclei MR so difficult? 1. low physical sensitivity gyromagnetic ratio γ ~γ I(I + 1) e.g MHz/T 1 H, MHz/T 17 O low SNR 2. low biological abundance e.g. 88 M 1 H, 80 mm 23 Na 3. low isotope percentage e.g % 13 C isotope 4. fast bi-exponential decay (spin 3/2) e.g. T2 of 1 H: 2 s, T2 of 23 Na: 50 ms 5. dedicated hardware Example: relative sensitivity of 23 Na is 1/13000 of 1 H = best case among X-nuclei Ruomin Hu I Slide 49 I What we can do to increase SNR 1. increase voxel size ( x) (worse spatial resolution) 2. increase magnetic field strength (B 0 ) (expensive and technically challenging) 3. increase readout duration (T RO ) (restricted by T2* decay) low SNR 4. increase acquisition time (T AQ ) and/or number of averages (prolonged measurement time) SNR~ x 3 T2 T1 B 0 x TRO T AQ (x = 1, sample dominated noise; x = 7/4, electrical dominated noise) M 0 ~1/T 5. dedicated hardware (coils have to be pre-matched to maximize efficiency) 6. lower temperature (T) (cannot lower body temperature) 7. use optimized pulse sequence and image reconstruction techniques Ruomin Hu I Slide 50 I

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