Functional Magnetic Resonance Imaging at 4.0 T

Improved Functional Magnetic Resonance Imaging at 4.0 TKimberly BrewerPhD Internal Defense Physics and Atmospheric ScienceJanuary 22, 2010

MRI and RelaxationxyzxyzM90ot < 0xyzMt = 0R2 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 + R2K-Space and ImagesSignal collected as frequency and phase information build representation of image in k-spaceImage is complex has both magnitude and phase informationK-space traversal depends on gradient patternsUse rectilinear or spiral trajectories

FTMagnetization is precessing collect signal as frequency and phase information, which lets us build a representation of the object in k-space, once k-space is sufficiently collected, an image can be obtained, this image is complex has both magnitude and phase information3Functional MRI (FMRI) - BOLDBOLD Blood oxygen level-dependentDeoxy Hb is paramagnetic, oxy Hb is diamagneticMore deoxy Hb the MRI signalAfter stimulus, ratio of oxy Hb/deoxy Hb , causing in the MRI signalBOLD effect is R2*-weighted A R2*-weighted sequence is generally used for fMRIAt high fields, BOLD CNR increases

BOLD activation in the brain in response to stimulus; differing magnetic properties, activation means increase in MRI signal, effect is R2*-weighted4Susceptibility Field Gradients (SFGs)Occur in regions where the magnetic susceptibility changes rapidlyE.g. Inferior temporal, orbital frontalThe large magnetic field gradients cause rapid dephasing, leading to a short T2*Most fMRI sequences are R2*-weightedCauses signal loss and other artifacts like geometric distortion in these regionsNo fMRI activation in these regions, or activation is displacedThese effects are worse at higher magnetic fields

Traditional

IdealSFGs are problem at high fields, changes in magnetic susceptibility, cause dephasing R2* effect which leads to signal loss and distortion 5ObjectivesUnderstand differing artifact mechanisms in spiral functional imagingDevelop and study a novel pulse sequence for SFG regions Asymmetric spin-echo (ASE) spiral Develop and test automated z-shim routinesEvaluate the impact of z-shim ASE spiralEvaluate specificity characteristics of ASE spiralSpiral-In vs Spiral-OutSpiral-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?Spiral-in vs spiral-out introduce7

Previously Proposed TheoriesSpiral-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

Go through this faster?? Mention R2* dephasing8Phantom ModelMove to a more well-known model with well-defined field mapsAlso used one tube filled with air surrounded by water Cylinder placed perpendicular to the main magnetic fieldDipolar field pattern

Ignore multiple tubes9Spiral-In remains better than Spiral-OutArtifact patterns are clearly different rotated by 45o and signal is summing in different locationsWhat is causing differences in geometry and signal loss?Phantom modelSimulations accurately reproduce results seen in phantom using only input of field map and gradient waveformsSpiral-InSpiral-Out

Point out difference in artifact patterns; why different?; mention signal loss due to R2* dephasing10Does Signal Dephasing Make the Difference?Used a high-resolution field map (1024x1024) to simulate intravoxel dephasing each image pixel contains 64 field map pixelsSum 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* DephasingAdditional Number of Hypointense Pixels in Spiral-Out Compared to Spiral-InPredictedObservedTE = 45ms6.6%3611369TE = 90ms7.3%3731166Scale for no field map 0.0312Scale for field map 0.025

Based on average signal intensity in homogeneous region, this would translate to a difference of * pixels. When you actually look at the number of darkened pixels, or pixels that appear to exhibit signal dephasing, the number is far higher. 11Individual Simulations Point Spread Functions

A single pixel is blurred out in a circular pattern both spiral-in and spiral-outNumber of pixels in the blur remains the same for bothIntroduce signal displacement here concept of point spread function12Signal DisplacementGrey voxels are contributing signal to location indicated by starSignal is being displaced identically for both spiral-in and spiral-outMost assume that spiral-in has no displacementPoint spread functions; Introduce phase and how its a vector sum13Phase Coherence

Voxels contributing signal (added in order of decreasing signal magnitude)Signal Magnitude in Voxel

SFG Region

Voxels contributing signal (added in order of decreasing signal magnitude)Signal Magnitude in Voxel

Non-SFG RegionRed is spiral-in, blue is spiral-out; black voxels sum coherently and contribute to star14Conclusions Spiral-in/Spiral-outR2* intravoxel dephasing is not the dominant mechanismInter-voxel dephasing is the cause of differencesDiffering phase coherence combined with identical signal displacementSpiral-in has increased overall signal recovery and reduced apparent distortionCaveat - signal displacement is occurring for spiral-in

Has increased overall signal recovery change textInclude cautionary note about possibility of signal displacmentPoint spread functions 4cm

If Im going to choose a sequence to use for SFG regions, although I need to be mindful that there is signal displacement occurring in spiral-in, it has better signal recovery and reduced apparent distortion.15Ideal Sequence for SFG regionsMinimal 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)

TETE*TE*

TE*Asymmetric Spin-Echo (ASE) Spiral

Step through diagram mention equivalent weighting17Asymmetric Spin-Echo (ASE) SpiralSpiral-OutASE Image 1ASE Image 2

SNR Results

8 subjectsRed line indicates equivalent to spiral-out20fMRI Results

Spiral-OutASE Image 1ASE Image 2ASE Image 330s breath-holding task, 5 subjectsPercent Signal Change, SNR and CNR

% signal change increases from 1-3, SNR decreases from 1-322Conclusions ASE spiralEach individual image has reduced apparent geometric distortion and minimal signal lossAlthough SNR decreases with increasing R2-weighting, % signal change increases to compensateEach image has equivalent CNR Combining images gives higher SNR and has more active voxelsCan 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-shimSpiral-Out No Z-ShimSpiral-Out Z-ShimZ-shim Asymmetric Spin-Echo SpiralSelection of z-shim values requires automated routineFor 18 slices and three images (10 different z-shim values) 18000 possible combinationsASE Image 1ASE Image 2ASE Image 3ASE Triple spiralSNR ResultsNo significant differences!8 subjectsSFG AreasNon-SFG AreasfMRI ResultsNo difference in the amount of active voxels, nor their maximum z-scores30s breath-holding task, 7 subjectsConclusions Z-Shim ASE SpiralThe B0 algorithm (summed with SS) gave the best results not significantly different from the others, or from ASE spiralNo significant improvements in SNR or fMRI at group levelZ-shim results were highly variable at the individual levelSome individuals had great improvements (30-90%) in SNR, while some saw SNR decreases with the addition of z-shimMay 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 regionsZ-shim adds unnecessary time and complications with no additional benefitsASE 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 strengthsThe T2 of blood at high fields is quite shortAt 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 improvementsFor 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 taskAlternating at 8 Hz4 slices (3 mm)Slices centred and aligned along calcarine sulcus2 mm in-plane resolutionSequences: Spiral-in/out, spin-echo spiral-in/out, ASE spiralVenogram (1mm in-plane resolution) used for delineation of vesselsFMRI ResultsAverage % Signal Change (S/S) in Tissue and Vasculature% signal change doesnt change in vessel; increases in tissue with increasing ASE image number i.e. increasing R2-weighting; spin-echo images have greatest tissue % signal change32Sensitivity vs SpecificityThe increasing S/S in tissue is promisingLater ASE images clearly have elements in common with spin-echo imagesHowever, results thus far could be due to later ASE spiral images being less sensitive, not more specificNeed a better metric Use an individualized specificity analysisBased 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 FPRGenerate 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 vesselSpecificity CurveFPR = 50%FPR = 0%Conclusions - SpecificityThe later ASE spiral images have activation patterns similar to spin-echo imagesS/S increases with increasing R2-weighting in tissue but remains constant in vasculatureSpin-echo images have significantly higher S/S in tissue than in vessel, as do the later ASE imagesThe 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 usefulHas stronger activation (and more active voxels) The specificity curve is not significantly different than the 3rd imageCould help improve temporal resolutionMay be able to change TE/TE* to improve intravascular suppression

ConclusionsDiscovered that differences in artifact patterns between spiral-in and spiral-out are due to inter-voxel dephasingPhase coherence + signal displacementDeveloped a novel pulse sequence, ASE spiral, that is effective at recovering signal lost in SFG regions while maintaining significant BOLD contrastDetermined that z-shim offers no additional benefit to sequences that are already recovering signal in SFG regionsASE spiral does not benefit from the addition of z-shimDetermined 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 fMRICollaborators 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 activationAlso saw increasing S/S with increasing R2-weightingASE spiral is currently being used for a temporal lobe epilepsy studyHas 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 DirectionsFurther spiral-in/spiral-out simulationsUsing a realistic head model will give more accurate signal displacement informationComprehensive 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 techniquesUses a task to elicit activation in the temporal lobeWill determine the effectiveness of signal recovery using a cognitive taskMonte 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 imagesAlso need to investigate different image addition methodsMay be able to gain both specificity and sensitivity benefits in post-processing AcknowlegementsDr. Steven BeyeaDr. Chris BowenDr. Ryan DArcyCareesa LiuSujoy Ghosh-HajraDr. Martyn KlassenJanet MarshallJames RiouxLindsay CherpakTynan StevensJodie GawrylukErin MazerolleConnie AdsettAhmed ElkadyEveryone at IBD Atlantic

Walter C. Sumner FoundationQuestions?SNR ResultsfMRI ResultsASE 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 weightingZ-shim Asymmetric Spin-Echo SpiralCan use unique z-shim gradient (in red) for each individual ASE image Lead into slide with 3 images46Z-Shim Automated RoutinesPrescan-based routines Optimal combination must have sufficient SNR and large number of recovered voxelsMIP-based routine - Images are combined with a maximum intensity projection (MIP) in routineSS-based routine Images are combined with a sum-of-squares (SS) in routineB0 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 resultsTR = 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 taskAlternating 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

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