1. MOIRA (MOlecular Imaging with RAdionuclides) F. Garibaldi, gr. Coll. Sanita What: Design (and implement) a SPECT detector with submillimeter spatial resolution and adequate sensitivity suitable for molecular imaging of biological processes in vivo Why: Detect vulnerable atherosclerotic plaques in mice and stem cells distribution monitoring (infarction) It sets forth to probe the molecular abnormalities that are the basis of disease rather than to image the end effects of these molecular alterations. mouse The rat and mouse host a large number of human diseases. Therefore one can study disease progression and therapeutic response under controlled conditions. Molecular imaging : the in vivo characterization and measurement of biologic processes at the cellular and molecular level. Coronary hearth disease is a leading cause of death in western countries. Injuries are generated by unstable plaques. No way to detect the nature of plaques with standard techniques (angiography). The identification & treatment of vulnerable atherosclerotic plaques prior to rupture has great impact in health care PET (microPET) cannot attain the needed performances! Increases apoptosis (programmed death cell) occurs in vulnerable plaques compared to stable plaque of the same size Atherosclerotic vulnerable plaques imaging apoptosis by proper tracer (e.g. 99 Tc-HYNIC- Annexin-V) that binds to apoptotic cells

2. Simulations show that arrays of CsI(Tl) 0.6 x 0.6 mm2 coupled to H9500 PSPMTs Hamamatsu (or Burle MCP(smaller anode pixel size) or LaBr3 continuous are the best options. Individual channel readout at 10-20 KHz (1024 to 8192 channels) Coded apertures collimators Spatial resolution: ~ 500 m (~ minimum plaque size) Sensitivity : 10 cps/ Ci Area single module : ~ 10x10 cm2 We would like to build 1 detector out of 8 or one module out of 4 Submillimeter spatial resolution already obtained (FWHM=0.93 mm ) AND High sensitivity (~850cps/MBq) Both spatial resolution and sensitivity should be further improved Sensitivity 10 times smaller than required pinhole 0.5 mm

3. Simulations show that arrays of CsI(Tl) 0.6 x 0.6 mm2 coupled to H9500 PSPMTs Hamamatsu or LaBr3 continuous are the best options. Readout has to be able to acquire individual channels at rates 10-20 KHz (1024 to 8192 channels) Submillimeter spatial resolution already obtained with pointlike source.(FWHM=0.93 mm) Hign sensitivity (~850 cps/MBq) (factor ~ 30 with respect to the pinhole and 6 with respect to parallel hole ) Coded apertures collimators Pinhole - multipinhole Improve both spatial resolution and sensitivity

4. MOIRA (MOlecular Imaging with Radionuclides) … the in vivo characterization and measurement of biologic processes at the cellular and molecular level. (Weissleder, RSNA 2000) and molecular level. (Weissleder, RSNA 2000) It sets forth to probe the molecular abnormalities that are the basis of disease rather than to image the end effects of these molecular alterations. Imaging of specific molecular targets enables: earlier detection and characterization of disease; earlier and direct molecular assessment of treatment effects; more fundamental understanding of disease processes. mouse The rat and mouse host a large number of human diseases Opportunity to study disease progression / therapeutic response under controlled conditions non-invasively and repetitively in same animal And reasonable FOV Very difficult. It does not exists in the market With PET one cannot attain this s.r. moreover with SPECT there is more variety of molecules

5. MOIRA (MOlecular Imaging with RAdionuclides) F. Garibaldi, gr. Coll. Sanita What: Design (and implement) a SPECT detector with submillimeter spatial resolution and adequate sensitivity suitable for molecular imaging of biological processes in vivo Why: Detect vulnerable atherosclerotic plaques in mice and stem cells distribution monitoring (infarction It sets forth to probe the molecular abnormalities that are the basis of disease rather than to image the end effects of these molecular alterations. mouse -The rat and mouse host a large number of human diseases. Therefore study disease progression and therapeutic response under controlled conditions non-invasively and repetitively in same animal ca be made Molecular imaging : the in vivo characterization and measurement of biologic processes at the cellular and molecular level. Coronary hearth disease is a leading cause of death in western countries. Injuries are generated by unstable plaques PET (microPET) cannot attain the needed performances! Motivation: The identification & treatment of vulnerable atherosclerotic plaques prior to rupture has significant impact in health care Hypothesis - increased apoptosis (programmed occurs in vulnerable plaques compared to stable plaque of the same size Goal - to prove the hypothesis in a transgenic mouse model using SPECT imaging techniques Investigate stem cells ability to regenerate injured tissue by monitoring in vivo migration and homing (infarction) fo several days. Postmortem tissue analysis are presently the main tool to investigate such process. Aterosclerotic vulnerable plaques Stem cells

6. Caratteristiche insufficienti per lo studio di processi biologici in piccoli animali quindi

7. Sensitivity very important

9. Coded apertures System Resolution = 1.7 mm; Sensitivity = 10361 cpm/μCi @ 40 cm Parallel hole; LEHR System Resolution = 15.2 mm; Sensitivity = 1063 cpm/μCi @ 10 cm Diffusione di cellule staminali (CD34+) in topo Fig. 19 Clinical PET scanner vs coded apertures Testa di topo con diverse risoluzioni spaziali

11. Hamamatsu H8500 PS-PMT NaI(Tl) (pixellated; 1.2 pitch) MURA 14 masks High FoV, 1.1 mm pitch High Resolution, 0.7 mm pitch Si è visto che con rivelatore di dimensioni 50 x 50 mm 2 è possibile ricostruire le immagini in un DOF ragionevole. Luso di un rivelatore più grande (100 x 100 mm 2 ) consente una maggior flessibilità. Si possono usare maschere diverse, con numero di buchi maggiore e quindi più efficienti o con buchi più piccoli e quindi miglior risoluzione spaziale. Si costruiranno due maschere con caratteristiche diverse (maggiore efficienza o migliore risoluzione spaziale)

12. Reconstruction of a 122 keV point-like source using the coded apertures Submillimeter spatial resolution (FWHM=0.93 mm) Hign sensitivity (~850 cps/MBq) (factor ~ 30 with respect to the pinhole and 6 with respect to parallel hole) Uptake ratio 6:1 12 x 12 mm² Tumor Uptake ratio 6:1 8 x 8 mm² Tumor Uptake ratio 6:1 5 x 5 mm² Tumor Uptake ratio 6:1 3 x 3 mm² Tumor Uptake ratio 12:1 12 x 12 mm² Tumor Uptake ratio 12:1 8 x 8 mm² Tumor Uptake ratio 12:1 3 x 3 mm² Tumor Source-Background Uptake ratio 12:1 5 x 5 mm² Tumor High gain in SNR, tumors smaller than 5 mm visible? (rough simulation)

13. tumor 12 x 12 mm² uptake 1:12 (at 54.7 mm) phantom DoF thickness(36.4 mm) SNR = 100 ± 4 SNR = 65 ± 3 SNR = 51 ± 3 artifacts 3D Simulation measurement