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Improved Functional Magnetic Resonance Imaging at 4.0 T. Kimberly Brewer PhD Internal Defense – Physics and Atmospheric Science January 22, 2010. MRI and Relaxation. t < 0. t = 0. z ’. z ’. z ’. 90 o. R 2 – transverse signal decay rate due to spin-spin interactions (R 2 = 1/T 2 )

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Improved functional magnetic resonance imaging at 4 0 t

Improved Functional Magnetic Resonance Imaging at 4.0 T

Kimberly Brewer

PhD Internal Defense – Physics and Atmospheric Science

January 22, 2010

Mri and relaxation
MRI and Relaxation

t < 0

t = 0





  • R2– transverse signal decay rate due to spin-spin interactions (R2 = 1/T2)

  • R2* - effective transverse relaxation rate including local field inhomogeneities (R2* = 1/T2*)

  • R2* = R2 + R2’









K space and images
K-Space and Images

  • Signal collected as frequency and phase information – build representation of image in k-space

  • Image is complex – has both magnitude and phase information

  • K-space traversal depends on gradient patterns

    • Use rectilinear or spiral trajectories


Functional mri fmri bold
Functional MRI (FMRI) - BOLD

  • BOLD – Blood oxygen level-dependent

    • DeoxyHb is paramagnetic, oxy Hb is diamagnetic

    • More deoxyHb the MRI signal

    • After stimulus, ratio of oxy Hb/deoxyHb, causing in the MRI signal

  • BOLD effect is R2*-weighted

    • A R2*-weighted sequence is generally used for fMRI

  • At high fields, BOLD CNR increases

Susceptibility field gradients sfgs
Susceptibility Field Gradients (SFGs)

  • Occur in regions where the magnetic susceptibility changes rapidly

    • E.g. Inferior temporal, orbital frontal

  • The large magnetic field gradients cause rapid dephasing, leading to a short T2*

    • Most fMRI sequences are R2*-weighted

  • Causes signal loss and other artifacts like geometric distortion in these regions

    • No fMRI activation in these regions, or activation is displaced

  • These effects are worse at higher magnetic fields




  • Understand differing artifact mechanisms in spiral functional imaging

  • Develop and study a novel pulse sequence for SFG regions

    • Asymmetric spin-echo (ASE) spiral

  • Develop and test automated z-shim routines

  • Evaluate the impact of z-shim ASE spiral

  • Evaluate specificity characteristics of ASE spiral

Spiral in vs spiral out
Spiral-In vs Spiral-Out

  • Spiral-out used for functional MRI studies – bad in areas with strong susceptibility field gradients (SFG)

  • Spiral-in* developed in response, is more commonly used when imaging SFG regions – particularly at higher field strengths like 4T

Why are they different?

* Glover and Law, MagnReson Med46:515-522 (2001)

Previously proposed theories
Previously Proposed Theories


Spiral-In TE = 30 ms

Spiral-Out TE = 19 ms

Spiral-In TE = 41 ms

1. Glover and Law, Magn Reson Med46:515-522 (2001)

2. Li et al, Magn Reson Med55:325-334 (2006)

Phantom model
Phantom Model

  • Move to a more well-known model with well-defined field maps

    • Also used one tube filled with air surrounded by water

    • Cylinder placed perpendicular to the main magnetic field

    • Dipolar field pattern

Phantom model1
Phantom model

  • Simulations accurately reproduce results seen in phantom using only input of field map and gradient waveforms



  • Spiral-In remains better than Spiral-Out

    • Artifact patterns are clearly different – rotated by 45o and signal is summing in different locations

    • What is causing differences in geometry and signal loss?

Does signal dephasing make the difference
Does Signal Dephasing Make the Difference?

  • Used a high-resolution field map (1024x1024) to simulate intravoxel dephasing – each image pixel contains 64 field map pixels

  • Sum magnitude of signal from each image pixel in a circular ROI that encompasses the artifact pattern for both Spiral-In and Spiral-Out

  • Dephasing alone does not account for all of the difference in signal loss, nor does it account for the geometric differences between Spiral-In and Out!

Individual simulations point spread functions
Individual Simulations – Point Spread Functions

  • A single pixel is blurred out in a circular pattern – both spiral-in and spiral-out

    • Number of pixels in the blur remains the same for both

Signal displacement
Signal Displacement

  • Grey voxels are contributing signal to location indicated by star

  • Signal is being displacedidentically for both spiral-in and spiral-out

    • Most assume that spiral-in has no displacement

Phase coherence
Phase Coherence

Signal Magnitude in Voxel

Signal Magnitude in Voxel

Voxels contributing signal (added in order of decreasing signal magnitude)

Voxels contributing signal (added in order of decreasing signal magnitude)

SFG Region

Non-SFG Region

Conclusions spiral in spiral out
Conclusions – Spiral-in/Spiral-out

  • R2* intravoxel dephasing is not the dominant mechanism

  • Inter-voxel dephasing is the cause of differences

    • Differing phase coherence combined with identical signal displacement

  • Spiral-in has increased overall signal recovery and reduced apparent distortion

    • Caveat - signal displacement is occurring for spiral-in

Ideal sequence for sfg regions
“Ideal” Sequence for SFG regions

  • Minimal apparent geometric distortion

  • Maximum signal-to-noise ratio (SNR)

  • Optimal R2’-weighting for maximum BOLD contrast-to-noise ratio (CNR)

  • High specificity to activation patterns (less sensitivity to large vessels)

Asymmetric spin echo ase spiral
Asymmetric Spin-Echo (ASE) Spiral


ASE Image 1

ASE Image 2

Snr results
SNR Results

8 subjects

Fmri results
fMRI Results


ASE Image 1

ASE Image 2

ASE Image 3

30s breath-holding task, 5 subjects

Conclusions ase spiral
Conclusions – ASE spiral

  • Each individual image has reduced apparent geometric distortion and minimal signal loss

  • Although SNR decreases with increasing R2-weighting, % signal change increases to compensate

    • Each image has equivalent CNR

  • Combining images gives higher SNR and has more active voxels

  • Can more optimization be done to further improve SNR and fMRI results?

Z shim gradients
Z-Shim Gradients

  • Z-shim gradients can be used to compensate for SFG gradients oriented along the slice direction (usually the largest voxel dimension)

  • Must acquire at least two images

    • One with z-shim & one without z-shim

Spiral-Out – No Z-Shim

Spiral-Out –Z-Shim

Z shim asymmetric spin echo spiral
Z-shim Asymmetric Spin-Echo Spiral

  • Selection of z-shim values requires automated routine

    • For 18 slices and three images (10 different z-shim values) – 18000 possible combinations

ASE Image 1

ASE Image 2

ASE Triple spiral

ASE Image 3

Snr results1
SNR Results

  • No significant differences!

SFG Areas

Non-SFG Areas

8 subjects

Fmri results1
fMRI Results

  • No difference in the amount of active voxels, nor their maximum z-scores

30s breath-holding task, 7 subjects

Conclusions z shim ase spiral
Conclusions – Z-Shim ASE Spiral

  • The B0 algorithm (summed with SS) gave the best results – not significantly different from the others, or from ASE spiral

  • No significant improvements in SNR or fMRI at group level

  • Z-shim results were highly variable at the individual level

    • Some individuals had great improvements (30-90%) in SNR, while some saw SNR decreases with the addition of z-shim

    • May be related to the base field inhomogeneities

  • Not really beneficial to add z-shim to a sequence that is already recovering signal in SFG regions (spiral-in)

  • ASE spiral is already optimized for SFG regions

    • Z-shim adds unnecessary time and complications with no additional benefits

Ase spiral specificity
ASE Spiral & Specificity

  • Spin-echo images are more specific to extravascular sources (i.e. tissue) compared to intravascular sources (i.e. vessels), particularly at high magnetic field strengths

    • The T2 of blood at high fields is quite short

    • At TE > 65 ms (4 T), less than 25% of spin-echo fMRI signal is intravascular

  • Increasing R2-weighting in later ASE spiral images may lead to specificity improvements

    • For most common TE/TE* combinations (ie. 60-70/30 ms), the third image has effective R2-weighting that is equivalent to a spin-echo spiral-in at TE = 90-100 ms.

  • Need to determine where ASE spiral activation is located and how it compares to pure gradient-echo and spin-echo sequences

Ase spiral specificity experiment
ASE Spiral Specificity Experiment

  • 12 healthy adults (3 males, 9 females)

  • 20 s alternating checkerboard task

    • Alternating at 8 Hz

  • 4 slices (3 mm)

    • Slices centred and aligned along calcarinesulcus

  • 2 mm in-plane resolution

  • Sequences: Spiral-in/out, spin-echo spiral-in/out, ASE spiral

  • Venogram (1mm in-plane resolution) – used for delineation of vessels

Sensitivity vs specificity
Sensitivity vs Specificity

  • The increasing ΔS/S in tissue is promising

  • Later ASE images clearly have elements in common with spin-echo images

  • However, results thus far could be due to later ASE spiral images being less sensitive, not more specific

    • Need a better metric – Use an individualized specificity analysis

  • Based off of ROC curves, is a function of the false positive rate (FPR) (i.e. the number of false positives – activation on veins, and the number of true negatives – voxels in vessels with no activation)

    • specificity = 1 – FPR

    • Generate specificity curves as a function of varying z-thresholds – the faster a curve reaches a value of 1.0 (i.e. no false positives), the more specific the sequence is to tissue compared to vessel

FPR = 50%

FPR = 0%

Conclusions specificity
Conclusions - Specificity

  • The later ASE spiral images have activation patterns similar to spin-echo images

  • ΔS/S increases with increasing R2-weighting in tissue but remains constant in vasculature

    • Spin-echo images have significantly higher ΔS/S in tissue than in vessel, as do the later ASE images

  • The 2nd and 3rd ASE spiral images are more specific than a pure gradient-echo, but less specific than spin-echo

  • The 2nd ASE image may be the most useful

    • Has stronger activation (and more active voxels)

    • The specificity curve is not significantly different than the 3rd image

    • Could help improve temporal resolution

    • May be able to change TE/TE* to improve intravascular suppression


  • Discovered that differences in artifact patterns between spiral-in and spiral-out are due to inter-voxel dephasing

    • Phase coherence + signal displacement

  • Developed a novel pulse sequence, ASE spiral, that is effective at recovering signal lost in SFG regions while maintaining significant BOLD contrast

  • Determined that z-shim offers no additional benefit to sequences that are already recovering signal in SFG regions

    • ASE spiral does not benefit from the addition of z-shim

  • Determined that the individual ASE spiral have varying degrees of sensitivity and specificity to fMRI activation

    • The 2nd and 3rd ASE images are more specific to extravascular sources than either spiral-in or spiral-out

Future directions current impact
Future Directions – Current Impact

  • ASE spiral is currently being used to study white matter fMRI

    • Collaborators have found that ASE spiral is more sensitive to the detection of activation located in white matter (corpus callosum)

      • Increase from 21% to 100% of subjects with activation

    • Also saw increasing ΔS/S with increasing R2-weighting

  • ASE spiral is currently being used for a temporal lobe epilepsy study

    • Has successfully elicited activation throughout the temporal cortex in several subjects and is insensitive to signal loss around metal clips found in post-surgical patients

Future directions
Future Directions

  • Further spiral-in/spiral-out simulations

    • Using a realistic head model will give more accurate signal displacement information

  • Comprehensive study is currently be doing to compare ASE spiral and other SFG recovery methods (spiral-in/out & spiral-in/in) to traditional (EPI & spiral) and non-BOLD (spin-echo spiral-in/out and FAIR) fMRI techniques

    • Uses a task to elicit activation in the temporal lobe

    • Will determine the effectiveness of signal recovery using a cognitive task

  • Monte Carlo simulations would be useful for modeling the specific contributions (tissue vs vasculature) occurring in both grey and white matter for each of the individual ASE spiral images

  • Also need to investigate different image addition methods

    • May be able to gain both specificity and sensitivity benefits in post-processing


  • Dr. Steven Beyea

  • Dr. Chris Bowen

  • Dr. Ryan D’Arcy

  • Careesa Liu

  • SujoyGhosh-Hajra

  • Dr. MartynKlassen

  • Janet Marshall

  • James Rioux

  • Lindsay Cherpak

  • Tynan Stevens

  • Jodie Gawryluk

  • Erin Mazerolle

  • Connie Adsett

  • Ahmed Elkady

  • Everyone at IBD Atlantic…

Walter C. Sumner Foundation

Fmri results3
fMRI Results

Ase spiral vs spiral out
ASE Spiral vs Spiral-Out

  • 8 healthy adults (4 males, 4 females)

  • 30 s breath-holding task

    • 3 subjects were excluded from fMRI results

  • TR = 3 s, 13 slice (5 mm, gap 0.5 mm)

  • 64 x 64 (240 x 240 mm) resolution

  • Spiral-out: TE = 25 ms

  • ASE spiral: TE* = 25 ms, TE = 70 ms

  • Multiple images were combined with equal weighting

Z shim asymmetric spin echo spiral1
Z-shim Asymmetric Spin-Echo Spiral

  • Can use unique z-shim gradient (in red) for each individual ASE image

Z shim automated routines
Z-Shim Automated Routines

  • Prescan-based routines – Optimal combination must have sufficient SNR and large number of recovered voxels

    • MIP-based routine - Images are combined with a maximum intensity projection (MIP) in routine

    • SS-based routine – Images are combined with a sum-of-squares (SS) in routine

  • B0 field routine – Developed by Truong and Song (2008)

    • Calculates offsets from an initial field map and calculates the gradients necessary to provide opposing phase twist

* Truong et al., MagnReson Med59:221-227 (2008)

Z shim ase spiral vs ase spiral
Z-Shim ASE Spiral vs ASE Spiral

  • 8 healthy adults (4 males, 4 females)

  • 24 s breath-holding task

    • 1 subject was excluded from fMRI results

  • TR = 4 s, 18 slice (5 mm, gap 0.5 mm)

  • 64 x 64 (240 x 240 mm) resolution

  • Z-shim ASE spiral & ASE spiral: TE* = 25 ms, TE = 70 ms

  • Images were combined with MIP or SS

Ase spiral specificity experiment1
ASE Spiral Specificity Experiment

  • 12 healthy adults (3 males, 9 females)

  • 20 s alternating checkerboard task

    • Alternating at 8 Hz

  • TR = 2 s (4-shot), 4 slices (3 mm, gap 0.5 mm)

    • Slices centred and aligned along calcarinesulcus

  • 128 x 128 (240 x 240 mm) – 1 mm in-plane resolution

  • Spiral-in/out: TE = 30 ms

  • Spin-echo spiral-in/out: TE = 105 ms

  • ASE spiral: TE* = 30 ms, TE = 75 ms

  • Venogram: 256 x 256, TE = 30 ms – used for delineation of vessels