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

2. 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?

3. 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)

4. 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)

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

6. 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)

7. 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

8. 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?

9. 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

10. 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)

11. 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

12. Raster-scan (2DFT) k-space acquisitionky 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

13. 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)

14. 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

15. 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

16. 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)

17. Multi-shot trajectories

18. 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

19. 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!!

20. 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?

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

22. 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)!

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

24. 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

25. 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)

26. 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]

27. 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…

28. 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

29. 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

30. 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?

31. 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

32. 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.

33. 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…

34. 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

35. 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?

36. 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?

37. 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

38. 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)

39. 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

40. 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

41. 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

42. Recommended Reading
Introduction to Functional Magnetic Resonance Imaging, by Buxton
Handbook of MRI Pulse Sequences, by Bernstein, King & Zhou
These slides: