Improved Functional Magnetic Resonance

Imaging at 4.0 T

Kimberly BrewerPhD External Defence – Physics and Atmospheric ScienceMarch 18, 2010

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MRI and Relaxation

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

• R2’ - transverse relaxation rate from local field inhomogeneities (R2’ = 1/T2’)

• R2* = R2 + R2’

B0

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 signalA 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

frontalThe large magnetic field

gradients cause rapid dephasingCauses signal loss and other

artifacts◦ No fMRI activation in these regions,

or activation is displacedEffects are worse at higher

magnetic fields

Traditional

“Ideal”

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

Spiral-In vs Spiral-Out

Spiral-In TE = 30 ms

Spiral-Out TE = 19 ms1. Glover and Law, Magn Reson Med 46:515-522 (2001)

TE

“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 extravascular sources

(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

ASE Spiral & SpecificitySpin-echo more specific to tissue compared to

vessel 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 intravascularIncreasing R2-weighting in later ASE spiral

images may lead to specificity improvements◦ Common TE/TE* combinations (ie. 60-70/30 ms)

- third ASE image has effective R2-weighting = a spin-echo spiral-in at TE = 90-100 ms.

Determine where ASE spiral activation is located◦ Compare to pure gradient-echo and spin-echo

FMRI Results

20s alternating checkerboard task, 12 subjects, 2mm in-plane resolution, 3mm thick

Average % Signal Change (ΔS/S) in Tissue and Vasculature

20s alternating checkerboard task task, 12 subjects

Sensitivity vs SpecificityLater ASE images similar to spin-echo images

◦ In appearance and in % signal changeHave not yet proved that later images are more

specific◦ Need a better metric – Use an individualized

specificity analysis with venogramBased off ROC curves - function of false positive

rate (FPR) ◦ Number of false positives – activation on veins; 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, the more specific it is to tissue compared to vessel

Specificity Curve

FPR = 50%

FPR = 0%

12 subjects

Conclusions - SpecificityThe 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

ConclusionsDeveloped a novel pulse sequence, ASE

spiral, that is effective at recovering signal lost in SFG regions while maintaining significant BOLD contrast

Determined that individual ASE spiral images 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

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?

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-

weightingASE 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

Conclusions - Specificity 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 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 – ASE spiralEach individual image has reduced

apparent geometric distortion and minimal signal loss

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

SNR Results

fMRI Results

ASE Spiral vs Spiral-Out8 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 HzTR = 2 s (4-shot), 4 slices (3 mm, gap 0.5 mm)

◦ Slices centred and aligned along calcarine sulcus128 x 128 (240 x 240 mm) – 1 mm in-plane

resolutionSpiral-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

ASE Spiral Specificity Experiment12 healthy adults (3 males, 9 females)20 s alternating checkerboard task

◦ Alternating at 8 Hz4 slices (3 mm)

◦ Slices centred and aligned along calcarine sulcus

2 mm in-plane resolutionSequences: Spiral-in/out, spin-echo

spiral-in/out, ASE spiralVenogram (1mm in-plane resolution) – used

for delineation of vessels