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Novel High resolution SPECT Instrumentation and Techniques for Molecular Imaging of Small Animals F. Garibaldi - ISS-NIH, Rome, 4-6 June 06 Novel High.

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Presentation on theme: "Novel High resolution SPECT Instrumentation and Techniques for Molecular Imaging of Small Animals F. Garibaldi - ISS-NIH, Rome, 4-6 June 06 Novel High."— Presentation transcript:

1 Novel High resolution SPECT Instrumentation and Techniques for Molecular Imaging of Small Animals F. Garibaldi - ISS-NIH, Rome, 4-6 June 06 Novel High resolution SPECT Instrumentation and Techniques for Molecular Imaging of Small Animals F. Garibaldi - ISS-NIH, Rome, 4-6 June 06 specific task vulnerable plaques -detecting vulnerable plaques in mice what you need -high resolution high sensitivity -high resolution high sensitivity detectors key parameters: - SNR - FOV - Sensitivity - Sensitivity - Spatial Resolution - Spatial Resolution - simulations, prel. measurements Summary and outlook Molecular imaging with radionuclides :the in vivo characterization and measurement of biologic processes at the cellular and molecular level 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 PET (microPET) cannot attain the needed performances ! MRI doesn’t have the needed sensitivity Collaboration between ISS, JHU(B. Tsui), Jefferson Lab (S. Majewski)

2 Molecular Imaging Modalities CT Tissue Density, Z A 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 < mole = quantitative F Unique !!

3 γ Imaging: Single Photon Detector Module Patient injected with radioactive drug. Drug localizes according to its metabolic properties. Gamma rays, emitted by radioactive decay, that exit the patient are imaged. 1.Collimator Only gammas that are perpendicular to imaging plane reach the detector 2.Scintillator Convert gammas to visible light 3.Photomultiplier Convert light to electrical signal 4.Readout Electronics Amplify electrical signal and interface to computer 5.Computer decoding procedure Elaborate signal and gives image output

4 High Resolution High Sensitivity Detectors key parameters SNR (and contrast) (spatial resolution) S = counts in ROI, BKG = background Max = max. counts in tumor ROI energy resolution plays only a secondary additional role in imaging breast under compression they are correlated FOV Diffusive Wall FWHM = 7.4 mm Absorbing Wall FWHM = 5.4 mm Light Spread Function (LSF) Gamma Emission X position

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6 CsI(Tl) Bialkali PMT Important parameters for detectability/visibility - SNR - Contrast - SNR - Contrast time (and modality) pixel dim/n.of pixels scintillator electronics, DAQ detector and collimation modality (compression) efficiency. Uniformity of p.h.response (affecs the overall en res. and the energy window sel.) spatial resolution  fotofraction Bialkali PMT uptake (radiopharmacy) detector intrinsic properties

7 Importance of pixel identification good pixel identification is fundamental for correct digitization affecting spatial resolution and contrast C8 strips M16 (4 x 4) mm 2 M64 (2 x 2) mm 2

8 4096 Ch. -> 8192 Ch. (10-20 kHz) Under study Projective coordinate electronics 1024 ch, 2 KHz

9 NaI(Tl) 1.2 pitch H9500 (3x3 mm2) tum 8 mm tumors: (5, 6, 7, 8,9,10,12) uptake 1:10; breast 6 cm NaI(Tl) 1.5 pitch; H8500 (6x6 mm2) NaI(Tl) 1.3 pitch; H8500(6x6 mm2) 6 mm 7 mm 8 mm X (H9500) measurements confirm simulation smaller scintillator pixel, higher SNR anode pixel has to be small measurements but 6 mm tumors visible

10 Geant 4 simulation - pixellated CsI(Tl) ( mm pitch) - LaBr3 continuous (3 mm thick, different surface(s) treatment(diffusive vs absorptive) - 6 x 6 mm 2, 3 x 3 mm 2, 1.5 x 1.5 mm 2 (PMT anode pixel size) 1000 counts/view/resol.elem. 1 plaque = 10 mCi,10resol.elem. aorta: ~ 2 mm diameter plaque size: 0.5 x 1 x 4 mm 3 system sensitivity: ~ 10 cps/  Ci detector area: 100 x 100 mm 2 spatial resolution: ~ 500  m Trying to Image apoptosis by proper tracer (e.g. 99m TcINIC-Annexin-V) Performances not good enough for imaging biological process in vivo in small animals (mice) ManRatMouse Body weight~70 kg~200 g~20 g Brain~105 mm~10 mm~6 mm Heart~300 g~1 g~0.1 g Aorthic cannula~ 30 mm1.5 – 2.2 mm mm (0.5 mm) manrat

11 0.6 mm pitch H mm pitch Burle Summary of CsI(Tl), pixellated What about CsI(Na) ?? LaBr3 to be carefully evaluated

12 Scaling down (100 mm, 0.8 mm --> 50 mm, 0.4 mm) 1/4 of detector area, 1/4 number of channels but 0.4 mm is very small !! mouse doesn’t scale !

13 but multiply by ~ 4 (multipinhole ) x 4(8) ( n. of modules)  snr = 30 ( 60 ) ===> plaque “visible” snr calculation simulation summary sensitivity too small

14 sensitivity smaller than required Submillimeter spatial resolution (FWHM=0.93 mm ) AND High sensitivity (~850cps/MBq) 30 time pinhole already obtained Both spatial resolution and sensitivity still to be improved Coded apertures Smaller scintillator pixels (0.8 --> 0.6 mm) ==> smaller photodetector anode pixels recostruction possible in a deepth of focus as large as large as 4 cm !! F. Cusanno et al. NIM A A  G =  then A  G = Ô, in fact There are decoding patterns G allowing: Ô = R  G = ( O × A )  G = O * (A  G) = O * PSF

15 Measurements 60 Co source, 122 keV NaI(Tl) 1.25 pitch H8500 (6 x 6 mm 2 ) CsI(Tl) 1.0 pitch H9500 (6 x 6mm 2 ) CsI(Tl) 1.25 pitch H9500 (3 x 3mm 2 ) measurements confirm simulations: small anode pixel is needed for small scintillator pixel (0.8 --> 0.6 mm --> high number of channels 1024 for 1 module! )

16 1.5mm thick LaBr3 attached to a H9500 PSPMT Image of a 0.25mm slit. Chipped edge seen at left. Non-uniformities to correct. Projection of the image of the slit. FWHM = 0.65mm Measured energy resolution ~ 8% keV Active area 0.75 mm FWHM Dead area 1.4 mm FWHM Mcarlo FWHM = Mcarlo FWHM = 0.8 LaBr3 continuous 1.5 mm thick + H9500 (3 x 3 mm2 anode); 3 mm thick + H8500(6 x 6 mm2) 3 mm mm thick LaBr3 attached to a H8500 PSPMT

17 Preliminary pinhole SPECT reconstruction results from the CsI detector Images are displayed as MIP (maximum-intensity-re-projections) animations Please use slide show mode to see the animation 2 point sources APOE mouse (kidneys shown) Flood image Sample projection image

18 Conclusions A solution for this challenging problem exists: - good results with CsI(Tl) 1 mm pitch + H pixels, spatial resolution 0.53 mm mm, FOV=33-25,  (22-39) cps/MBq improvements needed? scaling down (50 x 50 mm2, 0.4 mm pitch, Burle photodetector (3x3 mm2) ->more compact, much less expensive x 100 mm2 CsI(Tl) 0.8 (0.6) mm pitch with individual readout - careful evaluation of LaBr3 option (the advantage is better energy resolution (very important if multilabeling shows to be possible and useful) - Fov, surface treatment, thickness, availability, cost - decision SNR - decision to be taken on the base of SNR obtained with measurements (phantoms) Measurements for CsI(Na) mm pitch, LaBr3 3 mm thick 10 x 10 cm2 vs 5 x5 cm 2 (scaling down) (tomographic reconstruction will be decisive) Final layout on two steps next two years (if funding allows)

19 Invited talks Invited talks a Congressi Internazionali 1.F. Cusanno. “High Resolution, High Sensitivity detectors for Molecular imaging with Radionuclides: the Coded Aperture option”. Milos (Grecia). Imaging technologies in Biomedical Sciences. September F. Garibaldi. “High Resolution, High Sensitivity Detectors”, Advanced Molecular Imaging Techniques in the Detection, Diagnosis, Therapy, and Follow-Up of Prostate Cancer, Rome, 6-7 December 3. Magliozzi ML et al “High Resolution, High Sensitivity Detectors for Molecular Imaging of Small Animals and Tumor Detection”. International Conference of Advanced Detectors. Como (Italy), October17-21, F. Garibaldi, “Molecular imaging: high resolution detectors for early diagnosis and therapy of breast cancer”. Milos (Grecia). Imaging technologies in Biomedical Sciences. September "Molecular Breast Imaging: first results from Italian National Health Institute clinical trials", to be presented at the International Conference "Fist European Conference on Molecular Imaging Technology (EUROMEDIM2006)” Marseille, France, May E. Cisbani, “Imaging with radionuclides: a powerful means for studying biological processes in vivo", Fist European Conference on Molecular Imaging Technology (EUROMEDIM2006)", Marseille, France, May Cuba ?

20 Publications 1.F. Garibaldi et al. “ A PET scanner employing CsI films as photocathode ”, Nucl. Instr. Meth., 2004, A525, F. Garibaldi et al. “ Novel design of a parallax free Compton enhanced PET scanner ”, Nucl. Instr. Meth., 2004, A525, R. Pani, M.N. Cinti, F. Cusanno, F. Garibaldi et al “ Imaging detector designs based on Flat panel PMT ”, Nucl. Instr. Meth., 2004, A527, F. Cusanno et al. “ Molecular imaging by single-photon emission ”, Nucl. Instr. Meth., 2004, A527, F. Cusanno et al. “ Preliminary Evaluation of Compact Detectors for Hand-Held Gamma Cameras ”, Physica Medica, 2004, XX (2), 65 6.Pani R. Cinti, M.N., Cisbani, E.; Colilli, S.; Cusanno, F.; De Vincentis 6.Preliminary study of metabolic radiotherapy with 188-Re via small animal imaging, A. Antoccia, G. Baldazzi, M. Bello, D. Bernardini, P. Boccaccio, D. Bollini, F. de Notaristefani, F. Garibaldi, G. Hull, U. Mazzi, G. Moschini, A. Muciaccio, F.-L. Navarria, V. Orsolini Cencelli, G. Pancaldi, R. Pani, A. Perrotta, M. Riondato, A. Rosato, A. Sgura, C. Tanzarella, N. Uzunov, M. Zuffa Nuclear Physics B, Volume 150, January 2006, Pages Small animal imaging by single photon emission using pinhole and coded aperture collimation, Garibaldi, F.; Accorsi, G.; Fortuna, A.; Fratoni, R.; Girolami, B.; Ghio, F.; Giuliani, F.; Gricia, M.; Lanza, R.; Loizzo, A.; Loizzo, S.; Lucentini, M.; Majewski, S.; Santavenere, F.; Pani, R.; Pellegrini, R.; Signore, A.; Scopinaro, F.; Veneroni, P.; IEEE Transaction on Nuclear Science, Volume 52, Issue 3, Part 1, June 2005 Page(s):573 – New Devices for Imaging in Nuclear Medicine, Cancer Biotherapy & Radiopharmaceuticals, 19(1), , A PET scanner employing CsI films as photocathode, Nucl Instr Meth A525, 2004, Novel design of a parallax free Compton enhanced PET scanner Nucl Instr Meth A525, 2004,

21 11. A study of intrinsic Crystal-pixel light-output spread for discrete scintigraphic imagers modeling, Scafe, R.; Pellegrini, R.; Soluri, A.; Montani, L.; Tati, A.; Cinti, M.N.; Cusanno, F.; Trotta, G,Pan Pani, R.;Garibaldi,F.,IEEE Transaction on Nuclear Science, Volume 51, Issue 1, Part 1, Feb Page(s): Custom breast phantom for an accurate tumor SNR analysis, Cinti, M.N.; Pani, R.; Garibaldi, F.; Pellegrini, R.; Betti, M.; Lanconelli, N.; Riccardi, A.; Campanini, R.; Zavattini, G.; Di Domenico, G.; Del Guerra, A.; Belcari, N.; Bencivelli, W.; Motta, A.; Vaiano, A.; Weinberg, I.N.; IEEE Transaction on Nuclear Science, Volume 51, Issue 1, Part 1, Feb Page(s):

22 Publications - Molecular imaging by single-photon emission”, Nucl. Instr. Meth., 2004, A527, Preliminary Evaluation of Compact Detectors for Hand-Held Gamma Cameras”, Physica Medica, 2004, XX (2), Small Animal Imaging by Single Photon Emission Using Pinhole and Coded Aperture Collimation”, IEEE Tran Nucl Sci, 2005, 52(3), Tumor SNR Analysis in Scintimammography by Dedicated High Contrast Imager”, IEEE Trans Nucl Sci, 2003, 50(5), Custom breast phantom for an accurate SNR analysis, IEEE Trans. N.S., Vol 51, N.1 Feb Molecular imaging: high resolution detectors for early diagnosis and therapy monitoring of breast cancer, To be published on NIM, Milos -High Resolution, High Sensitivity Detectors for Molecular Imaging with Radionuclides: the Coded Aperture Option, to be published on NIM - Euromedim Francesco - Euromedim Evaristo - Euromedim Carrato -A. Dragone

23 1. “ A PET scanner employing CsI films as photocathode ”, Nucl. Instr. Meth., 2004, A525, “ Novel design of a parallax free Compton enhanced PET scanner ”, Nucl. Instr. Meth., 2004, A525, “ Imaging detector designs based on Flat panel PMT ”, Nucl. Instr. Meth., 2004, A527, “ Molecular imaging by single-photon emission ”, Nucl. Instr. Meth., 2004, A527, “ Preliminary Evaluation of Compact Detectors for Hand-Held Gamma Cameras ”, Physica Medica, 2004, XX (2), “ Small Animal Imaging by Single Photon Emission Using Pinhole and Coded Aperture Collimation ”, IEEE Tran Nucl Sci, 2005, 52(3), Milos code apertures 8. Milos breast? 9.Prostate Rome, in preparation 10.Invited talks at Euromedim (titoli anche se non so se mettere il breast) 11. Deleo et al (la PET del CERN sottomesso a NIM) 12.altri lavori (recenti) di PET CERN) 13.lavori dei nostri amici del pin diodes (IEEE CD?? ) 14.altra roba recente di Pani in cui ha messo solo me? 15.Como M.Lucia Invited talsk (presentazione a congressi): 1.Milos Milos Prostate Conference 4.Euromedim a Maggio 5.What else? (dal 2004)? 6.Como MLuci 7.Cuba?

24 P ositron E mission T omography microPET

25 Detection coincident events between two detectors Compton scatter equation relates scatter angle and E o and E re Photon direction is determined within conical ambiguity Internal Compton Probe Imaging Distance10 cm Compton Probe High-Sensitivity Coll. High-Resolution Coll. Efficiency Resolution 1.8e mm 1.11e mm 4.00e mm


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