Principles of nuclear magnetic resonance and MRI Review Chapter 3 Principles of nuclear magnetic resonance and MRI Review

Basic Physics of MRI Nuclei line up with magnetic moments either in a parallel or anti-parallel configuration. In body tissues more line up in parallel creating a small additional magnetization M in the direction of B0. Nuclei spin axis not parallel to B0 field direction. Nuclear magnetic moments precess about B0.

Larmor frequencies of RICs MRIs Basic Physics of MRI Frequency of precession of magnetic moments given by Larmor relationship f = g x B0 f = Larmor frequency (mHz) g = Gyromagnetic ratio (mHz/Tesla) B0 = Magnetic field strength (Tesla) g ~ 43 mHz/Tesla Larmor frequencies of RICs MRIs 3T ~ 130 mHZ 7T ~ 300 mHz 11.7T ~ 500 mHz

Basic Physics of MRI NMRable Nuclei Body 1H content is high due to water (>67%) Hydrogen protons in mobile water are primary source of signals in fMRI and aMRI

Basic Physics of MRI M is parallel to B0 since transverse components of magnetic moments are randomly oriented. The difference between the numbers of protons in the parallel (up here) and anti-parallel states leads to the net magnetization (M). Proton density relates to the number of parallel states per unit volume. Signal producing capability depends on proton density. B0

RF pulse duration and strength determine flip angle Basic Physics of MRI Frequency of rotation of M about B1 determined by the magnitude (strength) of B1. RF pulse duration and strength determine flip angle Basic RF Pulse Concepts RF Pulse strength duration

Basic Physics of MRI FID = Free Induction Decay 90° RF pulse rotates M into transverse (x-y) plane Rotation of M within transverse plane induces signal in receiver coil at Larmor frequency. Magnitude signal dependent on proton density and Mxy. FID magnitude decays in an exponential manner with a time constant T2. Decay due to spin-spin relaxation.

Need for 180° Pulse - Spin Echo FID also diminishes due to local static magnetic field inhomogeneity Some spins precess faster and some slower than those due to B0 90° Blue one is fast precessing spins. Question: What is the time between 90 and 180 pulse? Note: to use vector concept to explain a common question concerning the180 flipping of both blue and red spins. 180° time TE/2- TE/2+ 180 ° RF pulse reverses dephasing at TE (echo time) Residual decay due to T2 Spin Echo Signal TE

Nuclear Magnetic Resonance (NMR) Signal: Spin Echo (SE) TR (repetition time) = time between RF excitation pulses 90o 180o 90o FID Spin Echo 90 itself is capable of generate a FID signal 90-180 pair used to obtain a spin-echo (SE) signal. Definition of TR TE. TE/2 TE/2 TE = time from 90o pulse to center of spin echo

Developing Contrast Using Weighting Contrast = difference in image values between different tissues T1 weighted example: gray-white contrast is possible because T1 differs between these two types of tissue

T1 and T2 T1-Relaxation: Recovery Recovery of longitudinal orientation of M along z-axis. ‘T1 time’ refers to time interval for 63% recovery of longitudinal magnetization. Spin-Lattice interactions. T2-Relaxation: Dephasing Loss of transverse magnetization Mxy. ‘T2 time’ refers to time interval for 37% loss of original transverse magnetization. Spin-spin interactions,and more.

Properties of Body Tissues T1 (ms) T2 (ms) Grey Matter (GM) 950 100 White Matter (WM) 600 80 Muscle 900 50 Cerebrospinal Fluid (CSF) 4500 2200 Fat 250 60 Blood 1200 100-200 T1 values for B0 ~ 1Tesla. T2 ~ 1/10th T1 for soft tissues

Basic Physics of MRI: T1 and T2 T1 is shorter in fat (large molecules) and longer in CSF (small molecules). T1 contrast is higher for lower TRs. T2 is shorter in fat and longer in CSF. Signal contrast increased with TE. TR determines T1 contrast TE determines T2 contrast.

Contrast, Imaging Parameters T1W T2W r - proton density SE – spin echo imaging GRE – gradient echo imaging Short TEs reduce T2W Long TRs reduce T1W

Making an Image k-space (frequency domain) A k-space domain image is formed using frequency and phase encoding

Two Spaces k-space Image space ky y FT-1 x kx FT Final Image Acquired Data Image space x y Final Image FT-1 FT MRI task is to acquire k-space image then transform to a spatial-domain image. kx is sampled (read out) in real time to give N samples. ky is adjusted before each readout. MR image is the magnitude of the Fourier transform of the k-space image

The k-space Trajectory Equations that govern 2D k-space trajectory kx = g 0t Gx(t) dt if Gx is constant kx = gGxt ky = g 0t’ Gy(t) dt if Gy is constant ky = gGyt’ The kx, ky frequency coordinates are established by durations (t) and strength of gradients (G).

Simple MRI Frequency Encoding: RF Excitation Slice Selection (Gz) Frequency Encoding (Gx) digitizer on Readout Exercise drawing k-space manipulation

Frequency Encoding Gradient (Gx) The k-space Trajectory Frequency Encoding Gradient (Gx) Move to left side of k-space. (0,0) ky Digitizer records N samples along kx where ky = 0 kx

Simple MRI Frequency Encoding: Spin Echo Excitation Slice Selection Frequency Encoding (Gx) digitizer on Readout Exercise drawing k-space representation

The K-space Trajectory 180 pulse Digitizer records N samples of kx where ky = 0

Frequency and Phase Encoding for 2D Spin Echo Imaging digitizer on Excite Slice Select Frequency Encode Phase Readout 90 180 kx ky

The 2D K-space Trajectory 180 pulse Digitizer records N samples of kx and N samples of ky

Gradient Echo Imaging Signal is generated by magnetic field refocusing mechanism only (the use of negative and positive gradient) Signal intensity is governed by S = So e-TE/T2* Can be used to measure T2* value of the tissue R2* = R2 + R2ih +R2ph (R2=1/T2) Used in 3D and BOLD fMRI

MRI Pulse Sequence for Gradient Echo Imaging Excitation Slice Selection Frequency Encoding Phase Encoding digitizer on Readout Ernst angle (E) for optimum SNR .

FLASH Pulse Sequence TR1 TR2 TRN crusher crusher TRN/2 TRN/2 TRN B1 TR1 TR2 refocus Gz TRN Gy crusher crusher Gx acquire TRN/2 B1 TRN/2 TRN Gz Gy crusher crusher TR2 Gx TR1 2D Gradient Echo RF (10-15 degrees) Short TR (10-50 msec) N= 256 (2.5-13 sec per slice) Fig. 3.19. Courtesy of Peter Jezzard.

3D Sequence (Gradient Echo) acq kz Gx read Gy phase Select & phase Gz ky B1 kx RF Scan time = NyNzTR Good for high resolution T1W images of brain

3D T1W brain image 0.8mm spacing Time = 25 min

2D Echo Planar Imaging (EPI) b) B1 refocus Gz Gy Gx acquire 2d Gradient Echo Entire 2D slice within one TR 64x64 or 128x128 Time per slice (30-50 msec) Whole volume (2-4 sec) Good for fMRI studies Fig. 3.20. Courtesy of Peter Jezzard.

FLASH Image T2* Weighted TE = 30 msec CSF is bright Signal loss and distortions due to local differences in magnetic field Sources of Contrast in Brain - Endogenous - BOLD - Exogenous - could be contrast agent (Gd based) - Other - Susceptibility R2* = net T2 relaxation rate = 1/T2* R2* = R2tis + R2ih + R2BOLD + R2suc Fig. 3.23 courtesy of Peter Jezzard.

Quantitative Measurements Using fMRI Review Chapter 8 Quantitative Measurements Using fMRI Review

T2* fMRI Signal

From Neural Activity to fMRI Signal Signalling Vascular response Vascular tone (reactivity) Autoregulation Metabolic signalling BOLD signal glia arteriole venule B0 field Synaptic signalling Blood flow, oxygenation and volume End bouton dendrite Complex relationship between change in neural activity and change in blood flow (CBF), oxygen consumption (CMRO2) and volume (CBV).

fMRI Bold Response Model time BOLD response, % initial dip positive BOLD response post stimulus undershoot overshoot 1 2 3 stimulus Initial dip 0.5-1sec Overshoot peak 5-8 sec + BOLD response 2-3% Final undershoot variable Deoxyhemoglobin BOLD signal Figure 8.1. from textbook.

Graded BOLD Response Graded change in signal for a) BOLD and b) perfusion (CBF). 3 minute visual pattern stimulation with different luminance levels. Note max BOLD change of 2-3 % and max CBF change of 40-50 %. Figure 8.2. from textbook. N=12 subjects.

Perfusion vs. Volume Change 30 second stimulation 3-second intervals DCBF rapid DCBV slow BOLD volume assessed using exogenous tracer that remains in blood. In rat experiments TC for DCBV similar to that for BOLD overshoot. Figure 8.4. from textbook. Mandeville et al., 1999

Measurement of Cerebral Blood Flow with PET or MRI (Arterial Spin Labeling - ASL) + 511 keV PET Method O-15 H20 Uses magnetically labeled arterial blood water as an endogenous flow tracer Potentially provide quantifiable CBF in classical units (mL/min per 100 gm of tissue) Detre et al., 1992

Arterial Spin Labelling z (=B0) inversion slab imaging plane excitation blood y x inversion white matter = low perfusion Gray matter = high perfusion ASL is an example of a motion contrast IMAGEperfusion = IMAGEuninverted – IMAGEinverted Perfusion is useful for clinical studies: how much blood is getting to a region, how long does it take to get there? www.fmrib.ox.ac.uk/~karla/

Hardware for MRI Review Chapter 5 Hardware for MRI Review

3T Siemens Trio 60 cm patient bore 40 mT/m max gradient amplitude per axis 200 T/m/sec slew rate 2nd order active shimming ~0.30 ppm B0 homogeneity over 40 cm sphere self shielded Shielding Shims Field Strength

A helium-cooled superconducting magnet generates the static field. Always on: only quench field in emergency. niobium titanium wire. Coils allow us to Make static field homogenous (shims: solenoid coils) Briefly adjust magnetic field (gradients: solenoid coils) Transmit, record RF signal (RF coils: antennas) MRI Scanner Anatomy

Superconductor Magnet

Necessary Equipment Magnet Gradient Coils RF Coil 3T magnet RF Coil (inside) Magnet Gradient Coils RF Coil

Magnet Shielding and Shimming Iron Shielding Magnet Shim coil Gradient coil RF coil Subject Shims superconducting static room temperature Figure 5.2 from textbook.

Gradient Coils Sounds generated during imaging due to mechanical stress within gradient coils.

Current and Gradient Pulse Shape b a. gradient current supplied (short rise time induces eddy currents) b. eddy currents oppose changing field w/o compensation c. gradient current supplied with eddy current compensation d. potential field vs time with eddy current compensation Jerry Allison.

dB/dt Effect (more eddy currents) Peripheral Nerve Stimulation dB/dt -- dE/dt dt is gradient ramp time dB/dt largest near ends of gradient coils spatial gradient of dE/dt also important dB dt

dB/dt / E-Field Characteristics of Stimulation Not dependent on B0 Gradients - 40mT/m (larger Bmax for longer coil) Gradient Coil Differences - strength (increases dB) and length (head vs. body determines site) Rise Time - shorter rise time means larger shorter dt and therefore larger dB/dt Other Disruption of nearby medical electronic devices Subject Instructions Don’t clasp hands - closed circuit, lower threshold Report tingling, muscle twitching, painful sensations

MRI Scanner Components

Same or different transmit and receive coil. Schematic of MRI System Exciter Synthesizer XMTR T/R switch RF Coil Preamp RCVR A/P RAM Host Pulse programmer Synthesizer, A/P XMTR, RCVR, T/R Shim driver coils Gradient Amps Gx, Gy, Gz Network Same or different transmit and receive coil. A/P - Array Processor RF, Shim, Gradient Coils inside magnet All but Host, RAM, and A/P in equipment room Figure 5.1b from textbook.

RF Coil RF Coils can transmit and receive RF signals (i.e. apply B1 and monitor Mxy) A typical coil is a tuned LC circuit and may be considered a near-field antenna

Comprehensive Receiving coils 7 standard configuration： QD head coil QD Neck Coil QD Body Coil NSM-P035 Permanent Magnet MRI QD Extremity Coil Flat Spine Coil Breast Coil

Surface Coils

RF Coil Uniformity and SNR 50 100 150 200 250 400 600 800 1000 1200 1400 Surface coil/head coil comparison 1 2 3 4 17 cm spherical phantom distance, mm b (1) (2) (3) (4) B1 directions indicated by color arrows. (1) two surface coils on opposite sides in phase. (2) two surface coils out of phase. (3) single surface coil on right side. (largest SNR) (4) head coil. (most uniform SNR) Figure 5.7 from textbook.

Stimulus Presentation / Monitoring

Additional Equipment Software Time-Line Control Stimulus E-Prime Software Time-Line Control Stimulus Monitor Response Synchronize timing with MRI

fMRI Study Time New Design Scanning Preprocessing Statistical Analysis 4+ hr (one instance) New Design Scanning Setup Scans Take down Preprocessing Statistical Analysis 1-1.5 hr/subject 15-20 min 45 min to 1 hr 15 min <2 hr/ subject  variable

fMRI Study – All Data Total Data per subject can be 0.5-1.0 gBytes Raw Data ~200 mBytes Motion Correction ~180 mBytes Other Corrections ~180 mBytes each possibly Spatial Normalization ~ 30 mBytes Statistical Analysis Statistical Parametric Image (128x128x20) < 1 MByte Statistical Parametric Map (2x SPI) > 1 MByte Total Data per subject can be 0.5-1.0 gBytes

Spatial and temporal resolution in fMRI Review Chapter 7 Spatial and temporal resolution in fMRI Review

Typical Paradigm Instruction Presentation stimulation timing fMRI responses time (s) Trial #1 Trial #2 Presentation Response Behaviour 5 Instruction Presentation stimulation timing Processing sensing decision Response plan motor Task Behavior BOLD signal time course presentation (black) processing (light grey) response (dark grey) Onset and Width of BOLD response as temporal measures. ---- Not time to peak ---- Figure 7.4 from textbook.

Estimating Neural Processing Time From BOLD Response Onset 350 300 250 200 150 -50 50 100   kinematic RT (ms) BOLD onset difference (ms) (b) V1 SMA M1 time fMRI response ampitude   (a) Figure 7.5 from textbook. Task – use joystick to move cursor from start box to target box as rapidly and accurately as possible (10 trials in multiple subjects). BOLD response – V1 (primary visual cortex), SMA (supplementary motor area), M1 (primary motor area) Analysis – D but not t increases with increasing reaction time (RT). Conclusion – Delay in reaction time from planning rather than execution of movement.

Estimating Neural Processing Time From from BOLD Response Width fMRI signal change from SPL Time after presentation (s) . 9 8 1 2 3 fMRI (b) 5 Trial A Trial B RT(A) RT(B) Task (a) Task – determine if one object could be rotated to match a second. Rotation angle varied by design. Press button yes or no. BOLD response – Superior Parietal Lobule (SPL) Analysis – Normalized width of BOLD response correlated with reaction time (RT). Conclusion – SPL intimately involved in mental rotation of object. (c) 1 6 2 8 4 Normalized width of BOLD response (s) R e a c t i o n T m ( s ) Figure 7.6 from textbook.

Selection of optimal pulse sequences for fMRI Review Chapter 6 Selection of optimal pulse sequences for fMRI Review

Advantages Disadvantages BOLD Highest activation contrast 2x-4x over perfusion complicated non-quantitative signal easiest to implement no baseline information multislice trivial susceptibility artifacts can use very short TR Perfusion unique and quantitative information low activation contrast baseline information longer TR required easy control over observed vasculature multislice is difficult non-invasive slow mapping of baseline information no susceptibility artifacts Table 6.1a. Summary of practical advantages and disadvantages of pulse sequences (derived from textbook)

Time/secs 1 2 4 3 Perfusion TI ASL 3 Perfusion Venous outflow Venous outflow No Velocity Nulling Velocity Nulling Arteries Arterioles Capillaries Venules Veins TI ASL Figure 6.1a Signal is detected from water spins in the arterial-capillary region of the vasculature and from water in tissues surrounding the capillaries. Relative sensitivity controlled by adjusting TI and by incorporating velocity nulling gradients (also known as diffusion weighting). Nulling and TI~1 sec makes ASL sensitive to capillaries and surrounds.

Time/secs 1 2 4 3 Arterial inflow (BOLD TR < 500 ms) GE-BOLD No Velocity Nulling Velocity Nulling Arteries Arterioles Capillaries Venules Veins Figure 6.1b Gradient Echo BOLD is sensitive to susceptibility perturbers of all sizes, and are therefore sensitive to all intravasculature and extravascular effects in the capillary-venous portions of the vasculature. If a very short TR is used may show signal from arterial inflow, which can be removed by using a longer TR and/or outer volume saturation.

Time/secs 1 2 4 3 Arterial inflow (BOLD TR < 500 ms) SE-BOLD No Velocity Nulling Velocity Nulling Arteries Arterioles Capillaries Venules Veins Figure 6.1c Spin Echo BOLD is sensitive to susceptibility perturbers about the size of a red blood cell or capillary, making it predominantly sensitive to intravascular water spins in vessels of all sizes and to extravascular (tissue) water surrounding capillaries. Velocity nulling reduces the signals from larger vessesl.

Gradient-echo RF Gx Gz Gy 90° TE ASL pulse TI Spin-echo 180° TE RF Gx Gz Gy ASL pulse TI 90° spin-echo 180° TE RF Gx Gz Gy 90° t t/2 Figure 6.2 Pulse sequence diagrams of (a) gradient echo, (b) spin echo, and (c) asymmetric spin echo EPI. The TE is shown at the center of 9-line k-space (typically 64 or more lines).  is the offset from center of k-space to echo. Additional pulses needed for ASL are indicated schematically.

Chapter 4 Ultrafast fMRI Review

Effects of Field Homogeneity R2* = R2 + R2mi +R2ma R2 = transverse relaxation rate due to spin-spin interactions and diffusion through microscopic gradients R2mi = transverse relaxation rate due to microscopic changes, i.e. deoxyhemoglobin R2ma = transverse relaxation rate due to macroscopic field inhomogeneity R2*a is relaxation rate during activation R2*r is relaxation rate at rest

4x4x4 mm3 2x2x2 mm3 Spin Echo Gradient Echo EPI Fig. 4.3 EPI obtained with TE= 60 and TR=3000 msec and 63 and 95 ky lines. Note recovery of signal loss in d vs c and ghosting in c.

For EPI where is the readout signal largest? gradient echo readout window r.f. read gradient TE dephase rephase Fig. 4.5 Gradient echo (GE) echo forms at center of readout window where area under rephasing gradient = area of dephasing gradient. Unlike spin echo dephasing is due to spatial difference in Larmor frequencies during application of gradients. First half of readout window is rephasing and second half is dephasing again. This process repeats at the center of readout window for each ky line in k-space for EPI. For EPI where is the readout signal largest?

RF Slice Read Phase a) Read Phase b) n n-1 1 n-1 2 n 2 1 Fig. 4.7 GE EPI pulse sequence and k-space organization of samples. What flip angle is used for EPI?

Effect of system parameters on EPI images for fixed field of view. Echo Spacing Resolution SNR Geometric distortion Increase gradient slew rate Reduced --- Increase sampling bandwidth (kx) Increase number of shots (interleaving ky) Increased Use of ramp sampling (similar to slew rate effect) Increase read matrix (kx) Increase phase matrix (ky) Increased* Increase field strength Table 4.1 from text. * actual resolution increase less than expected due to smoothing effect of signal decay.

fMRI methods for reduced k-space coverage Keyhole acquire full k-space as reference acquire reduced low-frequency k-space fMRI study fill in missing k-space from reference Half-Fourier acquire 50-60% of k-space starting at highest ky theoretical symmetry used to fill in missing ky

fMRI methods for reduced k-space coverage Sensitivity encoding (SENSE) Multiple RF coils with independent signal for each (parallel imaging) Calibration maps from full k-space each coil part of k-space 2X improvement EPI, 4X for GE UNFOLD Acquire k-space in sequential time segments time 1 acquire lines 1, 5, 9, 13 ... time 2 acquire lines 2, 6, 10, 14 ... time 3 acquire lines 3, 7, 11, 15 ... time 4 acquire lines 4, 8, 12, 16 ... reorder into k-space 4x faster per segment reduces inter echo distortions