Improved Functional Magnetic Resonance

Imaging at 4.0 T

Kimberly BrewerPhD Internal Defense – Physics and Atmospheric ScienceJanuary 22, 2010

MRI and Relaxation

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• 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)

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nal M

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oxel

SFG Region

Voxels contributing signal (added in order of decreasing

signal magnitude)

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nal M

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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