improved functional magnetic resonance imaging at 4.0 t kimberly brewer phd internal defense –...
TRANSCRIPT
Improved Functional Magnetic Resonance
Imaging at 4.0 T
Kimberly BrewerPhD Internal Defense – Physics and Atmospheric ScienceJanuary 22, 2010
MRI and Relaxation
x’
y’
z’
x’
y’
z’
M90o
t < 0
x’
y’
z’
M
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
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 patternsUse rectilinear or spiral trajectories
FT
Functional MRI (FMRI) - BOLDBOLD – Blood oxygen level-dependent
◦ Deoxy Hb is paramagnetic, oxy Hb is diamagnetic◦ More deoxy Hb the MRI signal◦ After stimulus, ratio of oxy Hb/deoxy Hb ,
causing in the MRI signal
BOLD effect is R2*-weighted ◦ A R2*-weighted sequence is generally used for
fMRIAt high fields, BOLD CNR increases
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
Traditional
“Ideal”
ObjectivesUnderstand 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-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
* Glover and Law, Magn Reson Med 46:515-522 (2001)
Why are they different?
Previously Proposed Theories
Spiral-In TE = 30 ms
Spiral-In TE = 41 ms
Spiral-Out TE = 19 ms
1. Glover and Law, Magn Reson Med 46:515-522 (2001) 2. Li et al, Magn Reson Med 55:325-334 (2006)
TE
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
• 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?
Phantom model
Simulations accurately reproduce results seen in phantom using only input of field map and gradient waveforms
Spiral-InSpiral-Out
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!
Signal Difference Between Spiral-In and Spiral-Out
due to R2* Dephasing
Additional Number of Hypointense Pixels in
Spiral-Out Compared to Spiral-In
Predicted Observed
TE = 45ms 6.6% 361 1369
TE = 90ms 7.3% 373 1166
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
Grey voxels are contributing signal to location indicated by star Signal is being displaced identically for both spiral-in and
spiral-out Most assume that spiral-in has no displacement
Phase Coherence
Voxels contributing signal (added in order of decreasing
signal magnitude)
Sig
nal M
ag
nit
ud
e in
V
oxel
SFG Region
Voxels contributing signal (added in order of decreasing
signal magnitude)
Sig
nal M
ag
nit
ud
e in
V
oxel
Non-SFG Region
Conclusions – Spiral-in/Spiral-outR2* 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
Minimal apparent geometric distortionMaximum 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)
TE
TE* TE* TE*
Asymmetric Spin-Echo (ASE) Spiral
Asymmetric Spin-Echo (ASE) Spiral
Spiral-Out ASE Image 1 ASE Image 2
SNR Results
8 subjects
fMRI Results
Spiral-Out
ASE Image 1
ASE Image 2
ASE Image 3
30s breath-holding task, 5 subjects
Percent Signal Change, SNR and CNR
Conclusions – ASE spiralEach 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 GradientsZ-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
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 Image 3ASE Triple spiral
SNR Results
No significant differences! 8 subjects
SFG AreasNon-SFG Areas
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 SpiralThe 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 & SpecificitySpin-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 Experiment12 healthy adults (3 males, 9 females)
20 s alternating checkerboard task
◦ Alternating at 8 Hz
4 slices (3 mm)
◦ Slices centred and aligned along calcarine sulcus
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
FMRI Results
Average % Signal Change (ΔS/S) in Tissue and Vasculature
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
Specificity Curve
FPR = 50%
FPR = 0%
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
Conclusions 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 ImpactASE 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 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
Acknowlegements Dr. Steven Beyea Dr. Chris Bowen Dr. Ryan D’Arcy Careesa Liu Sujoy Ghosh-Hajra Dr. Martyn Klassen Janet Marshall
James Rioux Lindsay Cherpak Tynan Stevens Jodie Gawryluk Erin Mazerolle Connie Adsett Ahmed Elkady Everyone at IBD
Atlantic…
Walter C. Sumner Foundation
Questions?
SNR Results
fMRI Results
ASE Spiral vs Spiral-Out
8 healthy adults (4 males, 4 females)30 s breath-holding task
◦3 subjects were excluded from fMRI resultsTR = 3 s, 13 slice (5 mm, gap 0.5 mm)64 x 64 (240 x 240 mm) resolutionSpiral-out: TE = 25 msASE spiral: TE* = 25 ms, TE = 70 msMultiple images were combined with equal
weighting
Z-shim Asymmetric Spin-Echo Spiral
Can use unique z-shim gradient (in red) for each individual ASE image
Z-Shim Automated Routines Prescan-based routines – Optimal
combination must have sufficient SNR and large number of recovered voxels
1. MIP-based routine - Images are combined with a maximum intensity projection (MIP) in routine
2. 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., Magn Reson Med 59:221-227 (2008)
Z-Shim ASE Spiral vs ASE Spiral8 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) resolutionZ-shim ASE spiral & ASE spiral: TE* =
25 ms, TE = 70 msImages were combined with MIP or SS
ASE Spiral Specificity Experiment12 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 calcarine sulcus
128 x 128 (240 x 240 mm) – 1 mm in-plane resolution
Spiral-in/out: TE = 30 msSpin-echo spiral-in/out: TE = 105 msASE spiral: TE* = 30 ms, TE = 75 msVenogram: 256 x 256, TE = 30 ms – used for
delineation of vessels