Design and simulation of micro-SPECT: A small animal imaging system

1. Freek Beekman and Brendan Vastenhouw Section tomographic reconstruction and instrumentation Image Sciences Institute University Medical Center Utrecht Design and simulation of micro-SPECT: A small animal imaging system

2. 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

3. Computed Tomography Cross-sectional images of the local X-ray attenuation in an object are reconstructed from line integrals of attenuation (“projection data”) using a computer 1979:Hounsfield and Cormack share Nobel Prize…..

4. Why Computed Tomography ?

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

6. Examples of Tomography • Anatomy • X-ray Computed Tomography • Magnetic Resonance Imaging (MRI) • Molecule distributions • Positron Emission Tomography (PET) • Single Photon Emission Computed Tomography (SPECT)

7. X-ray CT: Cross-sectional images of X-ray attenuation provide knowledge about anatomy

8. We are also curious how organs... …..are functioning in vivo

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

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

11. 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.

12. Collimated gamma-camera • 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. IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII <= Lead collimator Detector >

13. <= Slice of Tc-99m distribution Slice of SPECT image => • 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)

14. SPECT Technetium-99m Cardiac Perfusion Image

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

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

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

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

19. Example iteration process: ML-EM reconstruction brain SPECT 0 iterations 10 iterations 30 iterations 60 iterations

20. line integral model accurate PSF-model

21. Small animal molecular imaging using single photon emitters (micro-SPECT)

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

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

24. Mouse thyroid I-125 pinhole image Microscopic slide ~1 mm ~ 20 min. acquisition arrows indicate locations parathyroid glands

25. Pinhole imaging geometries for small animal imagingSPECT(micro-SPECT)

26. 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

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

28. Micro-SPECT

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

30. 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%) ~30 mm ~10 mm • Contact Freek beekman: f.beekman@azu.nl • +31 30 250 7779 • We need approx. 40 detector elements.