Design and simulation of micro-SPECT: A small animal imaging system Freek Beekman and Brendan...

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: f.beekman@azu.nl

+31 30 250 7779

We need approx. 40 detector elements.

~10 mm

~30 mm