AAPM 2006 - MRI Physics & Technology 8/1/2006 08:00 Overview • Excitation & Signal Collection Process • Gradients for Spatial Localization The Principles of Quantitative MRI • Measuring Tissue Volumes • Measuring NMR Properties of Tissues Geoffrey D. Clarke Dept. of Radiology • Tissue Physiology Measurements University of Texas Health Science Center at San Antonio • Tissue Biochemistry Measurements 1 2 B1 TX Field RF Nonuniformities • Directly related to current in TX coil • RF Nonuniformities are the Single Biggest Cause of Errors in qMRI – Depends on Q of coil & coil loading • Depends on TX Coil Geomtry • TX power auto-adjusted (pre-scan) • RF Nonuniformities Increase as the Bo-Field Increases – Values should be know to 1% – 1% = 0.086 dB • Dielectric Resonance Effects Become Pronounced at High Bo • TX nonlinearities • RF pulse droop 3 4 The B1 RF Magnetic Field NMR Signal z δv(t ) = ωo B1x,y M x, yδVs cos(ωot ) N S x y Principle of Reciprocity B1 ξ =− G ∂ G G ( m ⋅ B 1) where m is the (nuclear) ∂t magnetic dipole moment and 5 G.D. Clarke, UTHSCSA G G G B 1 = ( B x iˆ + B y ˆj ) 6 1 AAPM 2006 - MRI Physics & Technology 8/1/2006 08:00 FT Approximation RF Pulse Bandwidth (BW) BW is inversely proportional to RF pulse duration: TX sin x A sinc function ( x ) envelope on the r.f. pulse produces a nearly square excitation profile of the phantom… phantom….. FT time frequency TX FT time frequency time Slice select gradient is scaled based on BW & Gss: slice thickness = FT BW 2π BW ⋅ γ G frequency tp ss 7 8 Resonant Frequency Offset M M B = Bo+ΔΩ/γ Beff = B1x’y’+ΔΩz/γ B1 X’ Y’ Y’ Beff Mz Mx After 90o, Magnetization IS NOT on y’ X’ axis Magnetization X’ 1 My’ = real Mx’ = imaginary Mz does not contribute to signal 1 My Magnetization Beff ΔΩ/γ ΔΩ/γ 90o Sinc Pulse Profile 0.5 0 Mx -0.5 -1 -5 -2.5 0 2.5 5 0.5 Mz 0 -0.5 -1 -5 -2.5 0 2.5 My X’ 2 ms, 5-lobe, chemical shift refocused Y’ Y’ 9 10 Slice Selection 180o Sinc Pulse rf1 TX 1 My Magnetization Magnetization 1 0.5 0 Mx -0.5 -1 -5 -2.5 0 2.5 Frequency (kHz) 5 RX 0.5 Gsl 0 -2.5 0 2.5 Spin Echo time time time – Larmor frequency of spins varies with position – The flip angle depends on the local Larmor frequency and the frequency content of the RF field pulse – the RF pulse can be “crafted” to contain frequencies in only a specified range 5 Frequency (kHz) 2 ms, 5-lobe, chemical shift refocused 11 G.D. Clarke, UTHSCSA rf2 • If constant gradient field is on during the rf pulse: Mz -0.5 -1 -5 5 Frequency (kHz) Frequency (kHz) 12 2 AAPM 2006 - MRI Physics & Technology 8/1/2006 08:00 Slice Profile Variations Bloch Equations • Flip Angle varies with location • A set of simultaneous differential equations that describe the behavior of the magnetization under any conditions. – Due to B1, B0 nonuniformities • Non-linearity of Excitation (Bloch Eqns) – FT approximation invalid for big flip angles – Bloch simulator software http://www-mrsrl.stanford.edu/~brian/mritools.html • T1-weighting of excitation profile M (t)−M0 dMz (t) =γ[Mx(t)By (t)−MyBx(t)]− z dt T1 Magnetization along the z-axis dMx (t) M (t) =γ[My (t)Bz (t) − Mz By (t)]− x dt T2 Magnetization along the x-axis dMy (t) Magnetization along the y-axis dt = γ [Mz (t)Bx (t) − Mx Bz (t)]− M y (t) T2 13 14 Brain Hargreaves Poor RF Pulse Calibration B1 Field Mapping - Purpose a. Needed for accurate measurement of many NMR parameters, i.e. relaxation times b. Enables estimation of systematic errors in parameter measurement c. Enable correction of spatial sensitivity variation using reciprocity 180o Miscalibration of FSE rf pulses (left image) is corrected (right image) 15 16 B1 Field Mapping B1 Field Mapping - Methods • One-pulse Mx,y method a. One-pulse read Mx,y • Hard 1800o pulse preceding 2D field echo sequence Venkatsen et al. Magn Reson Med 1998; 40:592 b. Spin Echo (both pulses altered) • Bright center is maximum B1 Barker et al. BJR 1998; 71: 59-67 c. One-pulse read Mz • Ring pattern occurs at every 5% change in B1-field Vaughn et al. Mgn Reson Med 2001; 46: 24 17 18 Deichmann R et al. Magn Reson Med 2002; 47: 398 G.D. Clarke, UTHSCSA 3 AAPM 2006 - MRI Physics & Technology 8/1/2006 08:00 Dielectric Resonance Effect Image Uniformity at 3 Tesla 1.5T • Fields inside a sample of diameter, d, can be resonant when d = nλ • This can make the B1 field at the center of the sample larger than at the edges 3T • This effect is dampened as the conductivity of the sample increases • B1 field maps in a saline phantom (18 cm diameter) 19 20 RL Greenman et al. JMRI 2003, 17(6): 648-655 Dielectric Resonance Spin-Echo Sequence rf1 rf2 TX Spin Echo RX time Gsl time Gro Gpe time time Symbolizes gradient increment from excitation to excitation 21 Hoult DI, J Magn Reson Imag, 2000; 12:46-67 Gradient Subsystems 22 One Dimensional FT Bo(x) x Mag FT 23 G.D. Clarke, UTHSCSA ν 24 4 AAPM 2006 - MRI Physics & Technology 8/1/2006 08:00 MRI Gradient Fields MRI Geometric Distortions ωo = γ (Bo + xGx ) Sources of Error: • Gradient Amplitude Calibration • Machine dependent –Best about 1% error • PatientPatient-dependent • Gradient Non-linearities • Accessory device dependent • Eddy Currents 25 26 Eddy Currents Eddy Currents • The magnetic field produced by Eddy Currents have two time-dependent components: • Accelerating current in gradient coils (gradient pulse) causes induced currents in nearby metallic structures. – An offset of the Bo field – An additional gradient field • These currents produce magnetic fields which, in turn, oppose the magnetic fields of the gradient coils G G Bec (r , t ) = Δg (r , t ) + ΔBo (t ) 27 28 Eddy Current Pre-emphasis Gradient Waveforms Gradient to Magnet Ratio Gradient Current Eddy Current Actual Gradient Field G/R=0.8 G/R=0.6 In free space In magnet In magnet A. Whole body system. In magnet Gradient Current with Pre-Emphasis Actual Gradient Field 0 10 ms A. Microscopy system. 29 G.D. Clarke, UTHSCSA In free space In free space B. Whole body, G/R=0.6 In magnet 0 In free space 10ms B. Microscopy system 30 5 AAPM 2006 - MRI Physics & Technology 8/1/2006 08:00 Actively Screened Gradients Measuring Eddy Currents •Reduce gradient field strength outside of gradient coil former - Current in shield is opposite polarity •Reduces gradient field in imaging volume also - Improves magnet homogeneity •Each gradient coil is associated with a screen coil - Twice as many amplifiers required 31 32 De Deene Y et a. Phys Med Biol 2000; 45:1807-1823 MRI Gradient Fields Eddy Currents Gradient Nonlinearities are often tolerated as part of trade-offs with gradient field strength or coil size Time course of eddy current field offset following different numbers of gradient pulse units Manufacturers often apply gradient distortion corrections in order to make images appear to be distortion free Influences image quality parameters (SNR, spatial resolution, etc.) 33 34 http://www.nbirn.net De Deene Y et a. Phys Med Biol 2000; 45:1807-1823 Brain Volume Measurement Brain Volume Relationships White Matter “Basal” Gray Cerebellum • High agreement between qMRI volumetry and physical sections • qMRI volumetry is susceptible to high inter-observer variability • Problems greatest in those regions where tissue margins are poorly defined 35 Jelsing J NeuroImage 2005; 26: 57-65 G.D. Clarke, UTHSCSA 36 Jelsing J NeuroImage 2005; 26: 57-65 6 AAPM 2006 - MRI Physics & Technology 8/1/2006 08:00 Cartilage MRI Relaxation Times • T1: longitudinal relaxation time defines recovery of potential for next signal (T1=1/R1) • T2: transverse relaxation time defines rate of dephasing of MRI signal due to microscopic processes (T2=1/R2) • T2*: transverse relaxation time with Bo inhomogeneity effects added; defines rate of dephasing of MRI signal due to macroscopic and microscopic processes (T2*=1/R2*) Accuracy of 3T high and tends to be more reproducible than 1.5 T 37 38 Eckstein F et al. Arth & Rheum 2005; 52: 3132-3136 Longitudinal Relaxation Transverse Magnetization M = Mo (1- exp(-TR/T1) T2* Decay Mo T1 2T1 3T1 4T1 τ 39 Applications for T1 Images Factors Influencing T1 • Macromolecular concentration in cytosol • Tissue characterization • Contrast agent uptake studies • Water binding • Measurement of Tissue Perfusion • Measurement of Blood Volume • Water content • Gd and Fermoxide Contrast Agents 41 G.D. Clarke, UTHSCSA 40 42 7 AAPM 2006 - MRI Physics & Technology 8/1/2006 08:00 Inversion Recovery T1 Measurement Sequences 90o 180o • Inversion Recovery 180o 180o Spin Echo – 180o-90o-180o; the gold standard TI • Saturation Recovery – 90o-180o TE TR Inversion • Stimulated Echo – 90o-90o-90o Excitation Refocusing +Mo M = Mo (2 - exp[-TI/T1]) • Look-Locker Sequence (see below) TI -Mo 43 Look-Locker Sequence 44 Saturation Recovery for CMRI 180o αo αo αo αo αo Encode Encode Encode Encode Encode τ τ τ τ τ • Very sensitive to RF pulse errors • Magnetization recovery rate, T1* : T1* = τ ⎛ τ ⎞ − ln(cosα ) ⎜ T⎟ ⎝ 1⎠ 45 46 Higgins DM, Med Phys 2005; 32(6):1738-1746 T1 Parametric Maps For Accurate & Precise T1 • Never Assume RF Flip Angle is Correct – Varies over imaged slice due to slice profile – Flip angle must be calibrated across slice • Be careful in assuming magnetization has reached steady state between acquisitions (a) T1 Map of tubes of gel doped with Gd-DTPA (b) T1-weighted image of heart in short axis (c) T1 parametric map image of heart in (b) • T1’s calculated from short-acquisition period T1 sequence (SAP-T1) with varying delay times • Optimize sequence acquisition parameters to ensure maximal SNR • Always check that fitted conforms to assumed model 47 48 Higgins DM, Med Phys 2005; 32(6):1738-1746 G.D. Clarke, UTHSCSA 8 AAPM 2006 - MRI Physics & Technology 8/1/2006 08:00 Multi-Echo with 180o Pulses Multi-Echo Acquisitions Mo exp(-TE/T2) Mo exp (-TE/T2*) Mo exp(-TE/T2) Signal Strength Signal Strength Mo exp (-TE/T2*) 90o 180o SE3 o SE2 180 time 3*TE SE3 180o o SE2 180 Gslice SE1 TE 180o SE1 2*TE TE time 90o 180o TE >> 2*TE T2* Gread 3*TE Gphase 49 50 Longitudinal Magnetization Time Scale of Relaxation Calculation of T2 M xy = M o e − t / T2 ' Mo 1- exp (-TR / T1) ln M xy = − 1 / T2 t + ln M o Transverse Magnetization 100’s of ms ' ln( M xy / M o ) = slope = − 1 / T2 ' exp (-TE/T2*) T2 = − 1 / slope 10’s of ms 51 52 Eddy Current Effects on Slice Gel Dosimeters • Used for 3D Radiation Dosimetry QC a c b • Relies on direct relationship between relaxation rate, R2 (R2=1/T2) of gel following exposure and dose Ideal – no eddy currents worst case pre-gradient train RF pulse profiles used for T2-relaxometry a) Ideal profile calculated from Bloch equations b) profile showing the influence of eddy currents; c) pre-gradient pulse train establishes steady-state which regularizes the RF pulse profile 53 www.mgsresearch.com G.D. Clarke, UTHSCSA 54 De Deene Y et a. Phys Med Biol 2000; 45:1807-1823 9 AAPM 2006 - MRI Physics & Technology 8/1/2006 08:00 Effective Flip Angles B1 Changes with Slice Position Average transverse magnetization within a slice as a fraction of Mo for various slice positions for flip angles ranging from 0o to 360o 55 56 De Deene Y et a. Phys Med Biol 2000; 45:1825-1839 R2 Calibration De Deene Y et a. Phys Med Biol 2000; 45:1825-1839 T2* Parametric Imaging M xy = M o e−t / T2 ' * • Similar to T2 measurements but use gradient echo imaging with varying TE 57 58 Magnetization Transfer Contrast Contrast Agent Maps Multislice FSE: T1-weighted image Magnetization Transfer Contrast Enhances T2Weighted Appearance Parametric map of R2* 59 60 http://www.research.philips.com/ G.D. Clarke, UTHSCSA 10 AAPM 2006 - MRI Physics & Technology 8/1/2006 08:00 Magnetization Transfer Magnetization Transfer Ratio PROTON SPECTRUM MTR = 0 Frequency (Hertz) Magnetization Transfer Ratio (MTR) “Free” Water Lipids Mo − Ms Mo “Bound” Water 217 Hz Frequency (Hertz) • the difference of the saturated versus non-saturate images relative to the signal in the normal (nonsaturated images) 1500 Hz 0 61 MTR and Aging 62 Physiological Measurements Gray matter and white matter MTR images reveal a quadratic change with age that is primarily attributed to normal demylenation • Flow – bulk motion of blood and other fluids within body • Perfusion – amount of blood traveling through capillaries in ml/s/gm of tissue • Diffusion – random motion of spins in a homogeneous solution – Apparent Diffusion Coefficient – measured diffusion rate of water through tissue 63 64 Inglese & Ge, Top Magn Reson Imag 2004; 15:355-363 Attenuation Due to Diffusion DWI Basic Pulse Sequence δ A(TE ) = A(0) exp[−γ 2G 2 Dappδ 2α 2 (Δ − )] 4 Where: α=π/2; G is amplitude of diffusion sensitive gradient pulse; δ is duration of diffusion sensitive gradient; Δ is time between diffusion sensitive gradient pulses; Dapp is the apparent diffusion coefficient 65 90o 180o time G G δ δ Δ ( b = γ 2G 2δ 2 Δ − δ 3 ) 66 Stejskal EO & Tanner JE, J Chem Phys 1965. 42: 288-292 G.D. Clarke, UTHSCSA 11 AAPM 2006 - MRI Physics & Technology 8/1/2006 08:00 The b-value Anisotropic Diffusion • Controls amount of diffusion weighting in image • The greater the b-value the greater the area under the diffusion-weighted gradient pulses H2O – longer TE – stronger and faster ramping the gradients H2O Restricted diffusion along neural fibers 67 Diffusion-Weighted MRI 68 Hemispherical Hypoperfusion Images acquired 55 minutes after onset of aphasia, hemiplegia, and hemiparesis. Top. Conventional 1-shot EPI DWI B. SENSE EPI-DWI with R=3 shows reduced susceptibility artifacts in frontal brain b = 1000 s/mm2 T2-weighted Diffusion Time-to-peak Weighted Perfusion 69 70 Sunshine JL et al. Radiology 1999; 212: 325-332. Bammer R, Schoenberg SO. Top Magn Reson Imag 2004; 15: 129-158 Diffusion Fiber Tracking Diffusion-Weighted Breast MRI Diffusion tracks (red and blue) in the splenium of the corpus callosum selected with ellipsoid filtering volumes (black) Parametric maps calculated from biomodal exponential decay model: ( 71 Conturo et al. PNAS 1999; 96:10442. G.D. Clarke, UTHSCSA ) ( I = P1' exp − bD1' + P2' exp − bD2' Io ) 72 Paran Y et al. NMR Biomed 2004; 17:170-180 12 AAPM 2006 - MRI Physics & Technology 8/1/2006 08:00 Dephasing Due to Motion Diffusion Tensor Imaging • In anisotropic tissues (neural fibers, muscle fibers) scalar ADC depends on direction of diffusion sensitizing gradient Gslice time o +180 PHASE BLOOD: phase not zero • Diffusive transport of water can be characterized by an effective diffusion tensor TISSUE: phase equals zero time Phase Shift Due to Motion in a Gradient Field -180o • Direction of diffusion can be used to create a map showing orientation of myocardial fibers. t=0 73 74 Tseng et al. , Radiology 2000; 216: 128-139. Phase Contrast Imaging Phase Contrast Images Velocity Encoded Image PHASE +180o Two Signals: S1 = Ss + Sm ;S2 = Ss + Sm e(iϕm) where ϕm= γ ΔM1 υ (υ = velocity) Phase Difference time Velocity Compensated Image -180o PHASE +180o Motion Compensation Gradient (Bipolar) Applied TISSUE: phase equals zero in BOTH images ΔS =S2-S1 =Sm[e(iϕm)-1] =2iSmsin(ϕm/2) Phase difference - Δϕ = arg S2 - arg S1, then υ = Δϕ / (γ ΔM1) time Velocity Encoded Image -180o Complex difference - BLOOD: phase is DIFFERENT in each image 75 76 Phase Contrast Velocity Phase Contrast +Venc Stationary In Out In Out Phase Difference (degrees) No Flow Flow Velocity 29 cm/s 180o MRI Velocity (cm/s) Magnitude Velocity Encoding (Venc) -180o -Venc True Flow Velocity (cm/s) 77 G.D. Clarke, UTHSCSA 78 13 AAPM 2006 - MRI Physics & Technology 8/1/2006 08:00 Cardiac Output Partial Volume Effect Asc. Aorta Flow (l/min) 25 Stotal Stotal Smoving Smoving φmoving φ 15 10 5 0 -5 0 4 8 12 φmoving Cardiac Output = 4.01 L/min Stroke Volume = 68 ml Sstatic 79 Coronary Artery Flow A B C D 16 Cine Frame Number φ Sstatic 20 80 Gadolinium Uptake 81 82 Max Upslope Parametric Map Nonuniformity Correction Real-time TrueFISP cine study with GRAPPA ×2 was performed between two perfusion scans SInormalization= SIperf/SIcine Correct for overall effects Correct for baseline signal SIcorrection= SInormalization-SIbase 50 50 45 Anterior 45 Anterior Anteroseptal 40 Anteroseptal 40 Inferoseptal Inferoseptal Inferior 35 Inferior 35 Inferolateral Inferolateral SI (A.U.) SI (A.U.) Anterolateral 30 25 Anterolateral 30 25 20 20 15 15 10 10 5 5 MRI perfusion image 0 0 0 5 10 15 20 25 Tim e (s ec) 30 0 5 10 15 20 25 30 Tim e (sec) 83 G.D. Clarke, UTHSCSA Maximum upslope parametric map 84 14 AAPM 2006 - MRI Physics & Technology 8/1/2006 08:00 SUMMARY Data Analysis Results 3 Before undertaking qMRI: MPRI 2 1 in fe ri or in fe ro la te ra an l te ro la te ra l an te ri or an te ro se pt al in fe ro se pt al 0 Myocardial perfusion reserve index (MPRI) is not significantly different between segments in asymptomatic individuals after corrections Bullseye display depicts segmental MPRI from most apical slice (center ring) to most basal slice (outer ring) • • • • • Check gradient calibrations Understand gradient non-linearities Evaluate eddy currents Measure RF pulse changes in space Determine RF receive nonuniformities 85 Quantitative MRI Methods 86 Learn More Details … • Measuring things with MRI: –Diffusion Coefficients –Frequency of a signal –Relaxation rates (T1, T2 , MTC) –Velocity of motion –Volumes of tissues 87 G.D. Clarke, UTHSCSA 88 15