1. Recent Advances in Small Animal SPECT instrumentations and techniques F. Cusanno 1, M. Ballerini 1, E. Cisbani 1, S. Colilli 1, R. Fratoni 1, F. Garibaldi 1, F. Giuliani 1, M. Gricia 1, M. Lucentini 1, M. L. Magliozzi 1,2, S. Majewski 3, G. P. K. Mok 4, F. Santavenere 1, S. Torrioli 1,2, B. M. W. Tsui 4, P. Veneroni 1, Y. Wang 4 Frontiers in Imaging Science: High Performance Nuclear Medicine Imagers for Vascular Disease Imaging, Rome, 13 – 14 November 2006 1.Istituto Superiore di Sanità, Rome, ITALY 2. Università La Sapienza, Rome, ITALY 3.Jefferson Lab, Newport News VA, USA 4.Johns Hopkins University, Baltimora MD, USA

2. CT Tissue Density, Z A 20-50 µm  -galactocidase 0.1 µmole H / µmole 31 P MRIA H Concentration MF BOLD, DCE 0.1 mm UltrasoundStructure A F Doppler Optical (Bioluminescence, fluorescence) A Topography M ~10 3 cells  quantitative µm to mm PET/SPECTRadiotracer M ~1-2 mm <10 -12 mole = quantitative F Molecular Imaging : the Role of the SPECT Unique!

3. Monte Carlo to Design Advanced Detectors Collimation plays a fundamental role (B. Tsui, R. Accorsi) GEANT4-based simulations: For the intrinsic gamma-detector different designs are possible Quality of the position reconstructions depends on amplitude and spread of light at the photo-detection plane and reconstruction algorithm Electronics should be adequate to really take advantage of chosen design and photodetector (A. Walenta)

4.  Smaller pixel in principle may provide better position reconstruction, provided sufficient light sampling  Pixel dimension, light guide and photodetector(s) coupling impacts on performances, they are not indipendent Monte Carlo can predict the limit of the intrinsic spatial resolution for a given configuration Light Sampling

5. Array Image and Map Reconstruction (1) The Present

6. Possible Future Array Image and Map Reconstruction (2)

7. Application: Atherosclerotic Plaques in Mice 1.ApoE -/- Mice Model for studying patogenesis of the atherosclerosis If feeded with lipidic food, it spontanously develops atherosclerotic lesions very similar to human plaques 2.Correlation between the presence of apoptotic macrofages and level of vulnerability of the plaque 3. 99m Tc-Annexin V: radiotracer with very high uptake in apoptotic cells Foto e Autoradiografia di Aorta di topo dopo 37 settimane di dieta ricca di lipidi Apolipoprotein E Knockout Mice Detection using advanced small-animal SPECT system Plump A, Ann Med 29, (1997) Kolodgie FD et al, Am J Pathol 157, (2000) Mari C et al, J Nucl Med 43, (2002) P702

8. Why Studying Atherosclerosis in Mice First cause of death in the western countries Plaques develop slowly, silently and asimptomatically since youth, as accumulation of lipids, colesterhol, connective tissue on the vascular walls Rupture of vulnerable plaques manifests suddendly as cardiac attack Discrimination of vulnerable/stable plaques is fundamental for effective diagnosis Conventional technique (angiography) are not specific and invasive Conventional techniques (angiography):  are not specific  are invasive Goal: design a detection technique  specific for vulnerable plaque  not invasive

9. Parameters for Simulation Blankenberg FG et al, PNAS 95, (1998) Collimator: Pinhole, 0.3˚mm aperture, magnification factor 3 Scintillator: CsI(Tl) pitch 0.5/0.8˚mm, 3˚mm thickness CsI(Na) pitch 0.8˚mm, 3˚mm thickness LaBr 3 (Ce) continuous, 3 − 5 mm thickness PS-PMT (“offline”): Flat Panel H9500, anode size 3.0˚mm Burle Planacon 85021, anode side 1.5 mm Assumed radiotracer distribution: Liver 12%, Kidneys 56 %, Spleen 2%, 5% ejected  25 % is distributed in the tissue H 3.0 mCi di Tc 99m -Annexin-V, H Phantom size 8×3×2 cm 3  Surrounding Tissue Uptake ~ 600 Bq/mm 3  Plaque Uptake ~ 10÷20*600 Bq/mm 3 H Plaque size ~ 0.5 × 1 × 4 mm 3

10. Results of Simulation T/B ratio “Shallow” Plaque Mid-deep Plaque Evaluation of S/N ratio using analytic algorithm

11. Preliminary Studies @ JHU (1) Spatial Resolution  0.6 mm Detector setup: tungsten PinHole 0.3 mm aperture, magnification factor 3 Scintillator: CsI(Tl) 1.0 mm pitch Photodetector: 2x2 H9500 array Electronics: IDEAS F.E.C. 5053 and data acquisition

12. ApoE -/- mouse, 15-week old Detector setup: tungsten PinHole 0.3 mm aperture, magnification factor 3 Scintillator: CsI(Tl) 1.0 mm pitch Photodetector: 2x2 H9500 array SPECT Reconstruction of 64 one-min views using MIP (maximum- intensity-re-projections) alghoritm Preliminary Studies @ JHU (2)  Setup of SPECT with alive mouse

13. Stem Cell Studies

14. Conclusions Molecular imaging with radionuclides is a very powerful technique allowing studies of “in-vivo” biological process; Single-Photon modality generally allows longer studies than PET and it could use different tracers Spatial resolution does not have theoretical limit, better detector technology is continuosly improving performances Advanced SPECT systems are required (for ex.) in the study of atherosclerotic plaques with mice Others interesting studies (for ex. stem cells) could benefit the use of advanced small-animal SPECT devices THANK YOU FOR YOUR ATTENTION!