Contrast and Acquisition Functional MRI: Image Contrast and Acquisition Karla L. Miller FMRIB Centre, Oxford University

Functional MRI Acquisition Basics of FMRI FMRI Contrast: The BOLD Effect Standard FMRI Acqusition Confounds and Limitations Beyond the Basics New Frontiers in FMRI What Else Can We Measure? Basics of FMRI FMRI Contrast: The BOLD Effect Standard FMRI Acquisition Confounds and Limitations Beyond the Basics New Frontiers in FMRI What Else Can We Measure?

The BOLD Effect BOLD: Blood Oxygenation Level Dependent Deoxyhemoglobin (dHb) has different resonance frequency than water dHb acts as endogenous contrast agent dHb in blood vessel creates frequency offset in surrounding tissue (approx as dipole pattern)

The BOLD Effect Frequency spread causes signal loss over time BOLD contrast: Amount of signal loss reflects [dHb] Contrast increases with delay (TE = echo time)

Vascular Response to Activation neuron capillary HbO2 HbO2 dHb HbO2 HbO2 dHb dHb = deoxyhemoglobin HbO2 = oxyhemoglobin [dHb] O2 metabolism blood flow blood volume

Sources of BOLD Signal Neuronal activity Metabolism Blood flow Blood volume [dHb] BOLD signal Very indirect measure of activity (via hemodynamic response to neural activity)! Complicated dynamics lead to reduction in [dHb] during activation (active research area)

S(TE) = S0 e–TE R2* S(TE)  TE R2* BOLD Contrast vs. TE 1–5% change BOLD effect is approximately an exponential decay: S(TE) = S0 e–TE R2* S(TE)  TE R2* R2* encapsulates all sources of signal dephasing, including sources of artifact (also increase with TE) Gradient echo (GE=GRE=FE) with moderate TE

Functional MRI Acquisition Basics of FMRI FMRI Contrast: The BOLD Effect Standard FMRI Acquisition Confounds and Limitations Beyond the Basics New Frontiers in FMRI What Else Can We Measure?

The Canonical FMRI Experiment Stimulus pattern on off Predicted BOLD signal time Subject is given sensory stimulation or task, interleaved with control or rest condition Acquire timeseries of BOLD-sensitive images during stimulation Analyse image timeseries to determine where signal changed in response to stimulation

What is required of the scanner? image 1 2 3 … Must resolve temporal dynamics of stimulus (typically, stimulus lasts 1-30 s) Requires rapid imaging: one image every few seconds (typically, 2–4 s) Anatomical images take minutes to acquire! Acquire images in single shot (or a small number of shots)

Review: Image Formation Fourier transform ky kx k-space image space Data gathered in k-space (Fourier domain of image) Gradients change position in k-space during data acquisition (location in k-space is integral of gradients) Image is Fourier transform of acquired data

Raster-scan (2DFT) k-space acquisition ky kx Collect separate line each repetition period (TR) “Multi-shot”: image pieced together over multiple TR Images have few artifats, but take minutes to acquire

Echo-planar imaging (EPI) ky kx “Single-shot”: Collect entire image each TR Increase in acquisition speed (good for FMRI) Longer readout each TR (introduces image artifacts)

Partial k-space c+id a+ib aib cid ky kx If data doesn’t have phase errors, quadrants of k-space contain redundant information (Hermetian symmetry) Partial k-space: acquire half of k-space and “fill in” missing data based on symmetry

Partial k-space EPI ky kx Reduces TE (sacrifices some functional contrast) Must acquire slightly more than half (Hermetian symmetry is approximate) Slight blurring added to image

Spiral FMRI Currently, only serious alternative to EPI Short apparent TE (center of k-space acquired early) Fast and efficient use of gradient hardware Reconstruction must resample onto grid before FFT Different artifacts than EPI (not necessarily better)

Multi-shot trajectories

Trajectory considerations Longer readout = more image artifacts Single-shot (EPI & spiral) warping or blurring PR & 2DFT have very short readouts and few artifacts Cartesian (2DFT, EPI) vs radial (PR, spiral) 2DFT & EPI = ghosting & warping artifacts PR & spiral = blurring artifacts SNR for N shots with time per shot Tread : SNR   Ttotal =  N x Tread

Typical* FMRI Parameters Value Notes TE (echo time) 1.5T: 60 ms 3.0T: 30 ms Determines functional contrast, set ≈T2* TR (repeat time) 1–4 s No extra info < 1s; Poor resolution > 6s Matrix size 64x64 Limited by incurred warping/blurring Resolution 3x3x4 mm Limited by SNR, FOV and matrix size Flip angle 60-90º Set to Ernst angle (max tissue signal) * These values are typical, not fixed!!

Functional MRI Acquisition Basics of FMRI FMRI Contrast: The BOLD Effect Standard FMRI Acquisition Confounds and Limitations Beyond the Basics New Frontiers in FMRI What Else Can We Measure?

The BOLD Effect BOLD contrast is based on signal dephasing BOLD imaging requires long delay (TE) for contrast

Signal Dropout in BOLD Dephasing also occurs near air-tissue boundaries due to abrupt shift in magnetic susceptibility Sensitivity to BOLD effect implies problems near air-tissue boundaries (e.g., sinuses)!

BOLD Signal Dropout BOLD Non-BOLD Dephasing near air-tissue boundaries (e.g., sinuses) BOLD contrast coupled to signal loss (“black holes”)

Image Warping Position information is encoded in local frequency Multi-shot EPI Position information is encoded in local frequency Imperfections in magnetic field (frequency offsets) masquerade as information about position Signal from regions with offset gets misplaced Longer readouts leads to greater displacement

Field Offset Field map EPI Spiral field offset local warping local blur Object interacts with magnetic field, introduces local imperfections (first-order correction with “shim” fields) Field offset introduces phase accrual during readout EPI: field offsets warp image (PSF linear phase along y) Spiral: field offsets blur image (PSF has conical phase)

EPI Unwarping Can measure local frequency (“field map”) uncorrected corrected Can measure local frequency (“field map”) Estimate distortion from field map and remove it Field map correction introduces blurring [Jenkinson et al]

Timing Errors Timing errors delay readout along kx and/or ky 2DFT EPI Spiral Timing errors delay readout along kx and/or ky Analyze via k-space point-spread function (PSF) Shift in k-space  PSF modulates image phase Phase cancellation patterns in image (can be complicated) Many causes: hardware delays, eddy currents…

EPI Ghosting EPI Odd and even lines mismatch (e.g., due to timing errors, eddy currents) Causes aliasing (“ghosting”) To fix: measure shifts with reference scan, shift back in reconstruction “ghost” = + undersampled

Physiological “Noise” Thermal SNR Timecourse SNR 7T 3T 1.5T 7T 3T 1.5T voxel volume voxel volume Respiration, cardiac pulsation, neural networks Thermal SNR linear in voxel volume, B0 Physiological noise tends to be “BOLD-like”: increases with TE and B0

Functional MRI Acquisition Basics of FMRI FMRI Contrast: The BOLD Effect Standard FMRI Acquisition Confounds and Limitations Beyond the Basics New Frontiers in FMRI What Else Can We Measure?

Receive RF coils and SNR Volume coil SNR  receive volume Volume coils signal and noise from entire volume good coverage, moderate SNR Surface coils localize signal and noise reduced coverage, good SNR Multi-channel coils array of “independent” surface coils good coverage Surface coil 8-channel array

Parallel imaging (SENSE, SMASH, etc) Single coil 8-channel array Surface coils Coil sensitivity encodes spatial information Can “leave out” large parts of k-space Theory: For n coils, only need 1/n of k-space Practice: Need at least ~1/3 of k-space In general, incurs loss of SNR More coverage, higher resolution, faster imaging, etc.

FMRI at High Field (>3T) SNR and BOLD increase with field strength Physiological noise means practical gain is less Benefits: Resolution Problems: Artifacts, RF heating, wavelength effects…

High-resolution FMRI at 7T High-res 7T: 0.58 x 0.58 x 0.58 mm3 = 0.2 mm3 High-res 3T: 1 x 1 x 1 mm3 = 1 mm3 Conventional 3T: 3 x 3 x 3 mm3 = 27 mm3

Functional MRI Acquisition Basics of FMRI FMRI Contrast: The BOLD Effect Standard FMRI Acquisition Confounds and Limitations Beyond the Basics New Frontiers in FMRI What Else Can We Measure?

Sources of BOLD Signal Yes! (ASL) Maybe… No…? Probably (VASO) Neuronal activity Metabolism Blood flow Blood volume [dHb] BOLD signal Maybe… No…? Probably (VASO) BOLD ([dHb]) is a very indirect measure of activity Can MRI get closer to the action?

FMRI of Blood Flow: ASL z (=B0) excitation y x inversion slab imaging plane inversion excitation blood Perfusion: delivery of metabolites (via local blood flow) Arterial Spin Labeling (ASL): invert of in-flowing blood IMAGEperfusion = IMAGEuninverted - IMAGEinverted

FMRI of Blood Flow: ASL Time (s) grey matter (high perfusion) white matter (low perfusion) Perfusion image ASL “kinetic curve” 0.8 0.6 Signal change (%) 0.4 0.2 0.0 1 2 3 4 Time (s) Represents an interesting physiological parameter Quantitative: fit kinetic curve for perfusion in ml/100g/min Lower SNR than BOLD Limited coverage (~5 slices)

FMRI of Blood Volume: VASO [Lu et al, MRM 2003] Vascular Space Occupancy (VASO): null blood volume Invert everything (blood + tissue) Image when blood is at null point (no blood signal) Change in blood volume causes signal change

Diffusion Tensor Imaging (DTI) Diffusion direction Water diffusion restricted along white matter Sensitize signal to diffusion in different directions Measure along all directions, infer tracts

Diffusion Tensor Imaging (DTI) Color-coded directions x y z Tract-based connectivity Complementary information to FMRI FMRI: gray matter, information processing DTI: white matter, information pathways Tractography: tracing white matter pathways between gray matter regions

Recommended Reading Introduction to Functional Magnetic Resonance Imaging, by Buxton Handbook of MRI Pulse Sequences, by Bernstein, King & Zhou These slides: http://www.fmrib.ox.ac.uk/~karla/