design and simulation of micro-spect: a small animal imaging system freek beekman and brendan...
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Design and simulation of micro-SPECT:A small animal imaging system
Freek Beekman and Brendan Vastenhouw
Section tomographic reconstruction and instrumentation
Image Sciences Institute
University Medical Center
Utrecht
PRESENTATION OUTLINE
• Introduction in tomography• Tomography with labeled molecules (“tracers”).• Principles of SPECT• Image reconstruction• Ultra-high resolution SPECT for imaging small laboratory animals => Need for high resolution gamma detectors
Cross-sectional images of the local X-ray attenuation in an object are reconstructed from line integrals of attenuation
(“projection data”) using a computer
Computed Tomography Computed Tomography
1979: Hounsfield and Cormack share Nobel Prize…..
Why Computed Tomography ?Why Computed Tomography ?
We are curious how we, other people, We are curious how we, other people, animals, etc, look inside…...animals, etc, look inside…...
… … but we don’t like to (be) hurt !but we don’t like to (be) hurt !
ExamplesExamples of Tomography of Tomography
AnatomyAnatomy• X-ray Computed TomographyX-ray Computed Tomography• Magnetic Resonance Imaging (MRI)Magnetic Resonance Imaging (MRI)
Molecule distributionsMolecule distributions• Positron Emission Tomography (PET)Positron Emission Tomography (PET)• Single Photon Emission Computed Tomography (SPECT) Single Photon Emission Computed Tomography (SPECT)
X-ray CT: Cross-sectional images of X-ray attenuation provide knowledge about anatomy
We are also curious We are also curious how organs...how organs...
……..are ..are functioningfunctioning
in vivoin vivo
Molecular imagingMolecular imaging
•Emission tomographs (PET and Emission tomographs (PET and SPECT) are suitable SPECT) are suitable in vivoin vivo imaging imaging of of functions (blood perfusion, use of functions (blood perfusion, use of oxygen and sugar, protein oxygen and sugar, protein concentrations) concentrations)
•Uses low amounts of injected Uses low amounts of injected radiolabeled radiolabeled moleculesmolecules
PET and SPECT imaging enables mapping of PET and SPECT imaging enables mapping of of radiolabeled molecule distributionsof radiolabeled molecule distributions
What area in the brain is responsible for a task?What area in the brain is responsible for a task?
SPECT: Single Photon Emission Computed
Tomography
SPECT: Single Photon Emission Computed
Tomography
• Patient is injected with a molecule labeled with a
gamma emitter.
• For determination of travel direction detectors are
equipped with a lead collimator.
• To form an image, the travel direction of detected photons must be known.
• The collimator selects -quanta which move approximately perpendicular to the detector surface.
Detector >Detector >
IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII <= Lead <= Lead
collimator collimator
Collimated gamma-camera Collimated gamma-camera
• Slices are reconstructed (Filtered Back Projection (FBP) or Iterative Reconstruction).
• Resolution in humans: 6-20 mm• Resolution can be much better in small animals (< 1 mm)
<= Slice of Tc-99m distribution<= Slice of Tc-99m distribution
Slice of SPECT image =>Slice of SPECT image =>
SPECT Technetium-99m Cardiac Perfusion Image
IMAGE RECONSTRUCTION FROM IMAGE RECONSTRUCTION FROM PROJECTIONSPROJECTIONS
Analytical (Radon Inversion)Analytical (Radon Inversion)
Discrete (Statistical) MethodsDiscrete (Statistical) Methods
pp = M = M aa + + n n + + bb <=> <=>
pp j j = M= Mjijiaai i + n+ nj j + b+ bjj
aaii = activity in voxel i = activity in voxel ippjj = projection data in pixel j = projection data in pixel jbbjj = back-ground in pixel j (e.g. scatter) = back-ground in pixel j (e.g. scatter)nnjj = noise in pixel j = noise in pixel j
MMjiji = probability that photon is emitted in voxel I is detected in pixel j. = probability that photon is emitted in voxel I is detected in pixel j.
Attenuation, detector blur and scatter Attenuation, detector blur and scatter cancan be included. be included.
Estimate Estimate aa from above equation from above equation
SPECT reconstruction problemSPECT reconstruction problem
SPECT reconstruction matrix SPECT reconstruction matrix is complicated byis complicated by
• Detector blurringDetector blurring• AttenuationAttenuation• ScatterScatter• 3D reconstruction3D reconstruction
Simulation (or“re-projection”)
Iterative Reconstruction illustratedIterative Reconstruction illustrated
Object spaceObject space
EstimatedEstimatedprojectionprojection
MeasuredMeasured projectionprojection
““Error”Error” projectionprojection
““Compare”Compare”e.g. - or /e.g. - or /
Projection spaceProjection space
Current Current estimateestimate
“Back-projection”
Object error Object error mapmap
Update
0 iterations 10 iterations 30 iterations 60 iterations
Example iteration process:Example iteration process:
ML-EM reconstruction brain SPECT ML-EM reconstruction brain SPECT
line integral model accurate PSF-model
Small animal molecular imaging using single photon emitters
(micro-SPECT)
Expected contribution of micro-SPECT to science
• Partly replacement of sectioning, counting and Partly replacement of sectioning, counting and autoradiography.autoradiography.• Reduction of number of animals requiredReduction of number of animals required• Dynamic and longitudinal imaging in intact animalsDynamic and longitudinal imaging in intact animals• Contribution to understanding of gene functionsContribution to understanding of gene functions• Acceleration of pharmaceutical development Acceleration of pharmaceutical development • Breakthroughs in areas like cardiology, neurosciences, Breakthroughs in areas like cardiology, neurosciences, and oncologyand oncology• Extension of micro-SPECT technology to clinical Extension of micro-SPECT technology to clinical imaging (~2006)imaging (~2006)
In Vivo Nuclear MicroscopyIn Vivo Nuclear Microscopy(Eur J. Nucl. Med and Mol. Im., in press)(Eur J. Nucl. Med and Mol. Im., in press)
Golden micro-pinholes Golden micro-pinholes
=> Super High Resolution=> Super High Resolution
SEM image of gold alloy pinholeSEM image of gold alloy pinhole
20 min. acquisition20 min. acquisition
arrows indicate locations parathyroid glandsarrows indicate locations parathyroid glands
~1
mm
~1
mm
Microscopic slideMicroscopic slide
Mouse thyroidMouse thyroid
I-125 pinhole imageI-125 pinhole image
~~
Pinhole imaging geometries for small animal imaging
SPECT
(micro-SPECT)
• Spatial resolution clinical SPECT ~ 15 mm
• Spatial resolution current small animal SPECT and PET: 1.0-2.5 mm• Micro-SPECT= dedicated small animal SPECT. with resolution 0.2-0.4 mm
Effect of Resolution on Rat Brain phantom
2 mm 1 mm 0.5 mm 0.25 mm 0 mm 2 mm 1 mm 0.5 mm 0.25 mm 0 mm
State-of-the-art pinhole SPECT
A-SPECT: two pinholes.A-SPECT: two pinholes. Mouse rotates in tubeMouse rotates in tube
Thyroid of mouseThyroid of mouse (I-125)(I-125)
Mouse bone scanMouse bone scan(Tc-99m)(Tc-99m)
Micro-SPECT
Simulations: A-SPECT vs. Micro-SPECT
TruthTruth
Micro-SPECTMicro-SPECTA-SPECTA-SPECT
Finally: We need a ready set of detectors plus associated
electronicsSolid state?
SPECIFICATIONS• Energies of 30-140keV• Counting mode
– Capture efficiency >80% @140keV– Spatial resolution: 200 microns – Energy resolution (10-20%)
•Contact Freek beekman: [email protected]
+31 30 250 7779
We need approx. 40 detector elements.
~10 mm
~30 mm