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 ?

We are curious how we, other people, animals, etc, look inside…... … but we don’t like to (be) hurt !

Examples of Tomography Anatomy X-ray Computed Tomography X-ray Computed Tomography Magnetic Resonance Imaging (MRI) Magnetic Resonance Imaging (MRI) Molecule 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 how organs... …..are functioning in vivo

Molecular imaging Emission tomographs (PET and SPECT) are suitable in vivo imaging of functions (blood perfusion, use of oxygen and sugar, protein concentrations)Emission tomographs (PET and SPECT) are suitable in vivo imaging of functions (blood perfusion, use of oxygen and sugar, protein concentrations) Uses low amounts of injected radiolabeled moleculesUses low amounts of injected radiolabeled molecules

PET and SPECT imaging enables mapping of of radiolabeled molecule distributions What area in the brain is responsible for a task?

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 > IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII <= Lead collimator 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 SPECT image => Slice of SPECT image =>

SPECT Technetium-99m Cardiac Perfusion Image

IMAGE RECONSTRUCTION FROM PROJECTIONS Analytical (Radon Inversion) Discrete (Statistical) Methods

p = M a + n + b p = M a + n + b p j = M ji a i + n j + b j a i = activity in voxel i p j = projection data in pixel j b j = back-ground in pixel j (e.g. scatter) n j = noise in pixel j M ji = probability that photon is emitted in voxel I is detected in pixel j. Attenuation, detector blur and scatter can be included. Attenuation, detector blur and scatter can be included. Estimate a from above equation SPECT reconstruction problem

SPECT reconstruction matrix SPECT reconstruction matrix is complicated by Detector blurring Detector blurring Attenuation Attenuation Scatter Scatter 3D reconstruction 3D reconstruction

Simulation (or “re-projection”) Iterative Reconstruction illustrated Iterative Reconstruction illustrated Object space Estimatedprojection Measured projection projection “Error” “Compare” e.g. - or / Projection space Currentestimate “Back- projection” Object error map Update

0 iterations10 iterations30 iterations60 iterations 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 autoradiography. Partly replacement of sectioning, counting and autoradiography. Reduction of number of animals required Reduction of number of animals required Dynamic and longitudinal imaging in intact animals Dynamic and longitudinal imaging in intact animals Contribution to understanding of gene functions Contribution to understanding of gene functions Acceleration of pharmaceutical development Acceleration of pharmaceutical development Breakthroughs in areas like cardiology, neurosciences, and oncology Breakthroughs in areas like cardiology, neurosciences, and oncology Extension of micro-SPECT technology to clinical imaging (~2006) Extension of micro-SPECT technology to clinical imaging (~2006)

In Vivo Nuclear Microscopy (Eur J. Nucl. Med and Mol. Im., in press) Golden micro-pinholes Golden micro-pinholes => Super High Resolution SEM image of gold alloy pinhole

20 min. acquisition 20 min. acquisition arrows indicate locations parathyroid glands ~1 mm Microscopic slide Mouse thyroid I-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: mm Micro-SPECT= dedicated small animal SPECT. with resolution mm Effect of Resolution on Rat Brain phantom 2 mm 1 mm 0.5 mm 0.25 mm 0 mm

State-of-the-art pinhole SPECT A-SPECT: two pinholes. Mouse rotates in tube Mouse rotates in tube Thyroid of mouse (I-125) (I-125) Mouse bone scan (Tc-99m)

Micro-SPECT

Simulations: A-SPECT vs. Micro-SPECT Truth Micro-SPECT A-SPECT

Finally: We need a ready set of detectors plus associated electronics Solid state? SPECIFICATIONS Energies of keV Counting mode –Capture efficiency –Spatial resolution: 200 microns –Energy resolution (10-20%) Contact Freek beekman: We need approx. 40 detector elements. ~10 mm ~30 mm