1. -1- 1st European Conference on Molecular Imaging Technology 9-12 May 2006 9-12 May 2006 Investigation of the LabPET TM Detector and Electronics for Photon-Counting CT Imaging Philippe Bérard a, J. Riendeau b, C. M. Pepin a, D. Rouleau a, J. Cadorette a, R. Fontaine b, R. Lecomte a 1st European Conference on Molecular Imaging Technology Marseille 9-12 May 2006 a Department of Nuclear Medicine and Radiobiology b Department of Electrical and Computer Engineering Université de Sherbrooke, Sherbrooke, Québec, Canada

2. -2- 1st European Conference on Molecular Imaging Technology 9-12 May 2006 9-12 May 2006 IEEE NSS/MIC Portland, October 2003 (2 x 2 x 10 mm 3 ). Academy of Molecular Imaging, March 2004, Orlando FL (1 x 1 x 10 mm 3 ). 1 x 1 mm 2 single L(Y)SO pixel PET detector Standard NIM electronics Am 241  59.5 keV 1mm 3 source 74 MBq 2003 - 2004 1 week ! 5 sec/proj10 sec/proj 20 sec/proj 50 sec/proj 40 sec/proj 30 sec/proj

3. -3- 1st European Conference on Molecular Imaging Technology 9-12 May 2006 9-12 May 2006 Main Purpose  Develop a combined multi-modality scanner capable of obtaining anatomical & functional data using a single apparatus relying on the same detection system. 2.4 2.0 1.7 0.75 1.0 1.3  Conduct successful follow-up investigations of gene expression, disease progression and therapeutic outcome in small animal models. See poster # 191 Lecomte et al. Preliminary report on the LabPET™, a high-performance APD-based digital PET scanner for small animal imaging. Investigation of photon-counting mode CT performed using LabPET™ detectors and digital electronics. Molecular Imaging Involves highly specific probes

4. -4- 1st European Conference on Molecular Imaging Technology 9-12 May 2006 9-12 May 2006 Dose issue in follow-up studies Effects of radiation dose on small animals LD50/30 for mouse: ~ 5 – 7.5 Gy Doses in the range 5 - 200 cGy : induce cell resistance to subsequent therapeutic doses of radiation (“adaptive response” * ) Doses in the range 1 - 20 cGy : induce therapeutic effects on certain tumor cells *G.P. Raaphorst and S. Boyden, “Adaptive response and its variation in human normal and tumor cells”, Int. J. Radiat. Biol. 75, pp. 865-873, 1999. PET/CT dose objective: lower than 1 cGy Lower spatial resolution: Dose ~ Δx -4, PET scintillator ~ 2 x 2 mm 2 pixels Micro CT typical dose ranges 10 - 40 cGy (100 µm resolution, σ ~ 25 HU) ** **Lee et al. A flat-panel detector based micro-CT system: performance evaluation for small-animal imaging, Physics in Medicine and Biology, no.48, 2003. Ford, N. L., Thornton, M. M., Holdswoth, D. W. Fundamental image quality limits for microcomputed tomography in small animals, Med. Phys., vol. 30, no. 11, pp. 2869-2877, 2003.

5. -5- 1st European Conference on Molecular Imaging Technology 9-12 May 2006 9-12 May 2006 Advantages of photon counting CT: Each event has equal weight independent of energy  Elimination of weight factor proportional to energy of integration imaging  Closer to optimal weighting of E -3 * Threshold detection allows discrimination of noise and scatter *R.N. Cahn et al., “Detective quantum efficiency dependence on X-ray energy weighting in mammography”, Med. Phys. 26 (12), pp. 2680-2683, December 1999. Photon counting in CT Detector: high light output scintillators to detect low-energy X-rays, fast fluorescence to avoid pulse-pile-up  count-rate > 10 6 - 10 7 counts/s, the higher the better Requirements :

6. -6- 1st European Conference on Molecular Imaging Technology 9-12 May 2006 9-12 May 2006 BGOGSOLSOLYSOYSONaI(Tl)CsI(Tl) Decay Time (ns) 300604041702301000 Light Output (APD) 304080100105100210 Peak Emission (nm) 480430420 430410550 1/μ (mm) at 60 keV 0.400.170.600.621.730.440.29 Photoelectric probability (%) at 60 keV 979995 949899 1/μ (mm) at 511 keV 11.61512.212.6443124 Photoelectric probability (%) at 511 keV 442634 51822 Potential PET/CT Scintillators Photon-counting CT scintillator requirements: Suitable for PET Short decay time  to avoid pulse pile-up and dead time in the front-end processing electronics High light output  low X-ray energy threshold

7. -7- 1st European Conference on Molecular Imaging Technology 9-12 May 2006 9-12 May 2006 PET/CT Detector LYSO best combination of : high attenuation coefficient high light output fast decay time  PET and CT imaging in photon- counting mode Decay Time (ns) Light Output (APD) Peak Emission (nm) 1/μ (mm) at 60 keV Photoelectric probability (%) at 60 keV 1/μ (mm) at 511 keV Photoelectric probability (%) at 511 keV LYSO 41 100 420 0.62 95 12.6 34 The high photoelectric absorption  confines spatial resolution to the crystal of interaction reflector scintillator APD

8. -8- 1st European Conference on Molecular Imaging Technology 9-12 May 2006 9-12 May 2006 PET/CT Configuration Oxford instruments 3. Normal microfocus x-ray tube with off focal spot geometrical configuration and reconstruction. See TomXGam and PIXSCAN 1. Rod anode microfocus 2. Carbon nanotube cold cathode

9. -9- 1st European Conference on Molecular Imaging Technology 9-12 May 2006 9-12 May 2006 Materials and Methods Stepping motors move X-ray source and phantom Data counts transferred by serial link Motor controller 115200 steps over 360 o Acquisition with a limited number of detectors Step and shoot acquisition

10. -10- 1st European Conference on Molecular Imaging Technology 9-12 May 2006 9-12 May 2006 LabPET TM Electronics APD Detector Module APD Bias Regulators 16-ch CSP ASIC (0.18 µm) Free- running ADCs FPGA DSP LabTEP TM 1 ‘fast track’ module See poster # 180 Fontaine et al. Digital signal processing applied to crystal identification in positron emission tomography dedicated to small animals.

11. -11- 1st European Conference on Molecular Imaging Technology 9-12 May 2006 9-12 May 2006 Digitized CSP signal from X-ray source  A veto with a duration of 8 samples was programmed in the FPGA after threshold crossing to detect maximum Resulting non-paralyzable dead-time of 156 ns limits the count rate to 5.6 x 10 6 events/sec/channel. Signal rise time ~90 ns (at 50% ADC maximum dynamic range) Fast baseline restorer to enable fast count rate Sample number Sample value ~ 55 keV event 65 kV, 20  A d xd = 23 cm 0.6 mm Cu

12. -12- 1st European Conference on Molecular Imaging Technology 9-12 May 2006 9-12 May 2006 Electronics count-rate X-ray source and LabPET™ detector Non-paralyzable model m = recorded count rate n = true interaction rate  = system dead time: 156 ns 10 % dead time at 1.6 x 10 6 counts/s 25 % dead time at 2.0 x 10 6 counts/s Paralyzable component from the detector ! CSP saturation Charge integration time Scintillator decay time

13. -13- 1st European Conference on Molecular Imaging Technology 9-12 May 2006 9-12 May 2006 CT Image Acquisition Operation characteristics Voltage : 65 kV Current : 20 μA Filter : 0.6 mm Cu Distance x-ray source – phantom : 11.5 cm Distance phantom - detectors : 11.5 cm nb detectors : 16 Linear sampling : 2 mm (detector width) 180 projections, 0.1 second/projection  25 minutes scan time 1 second/projection  45 minutes scan time Parallel FBP reconstruction algorithm : Nyquist cutoff frequency

14. -14- 1st European Conference on Molecular Imaging Technology 9-12 May 2006 9-12 May 2006 Energy resolution of detector Energy spectrum used for image acquisition. Landmark for small animals : 20-30 keV mean energy. Higher light output desirable Better SNR Better energy resolution  Lower counting threshold

15. -15- 1st European Conference on Molecular Imaging Technology 9-12 May 2006 9-12 May 2006 Spatial Resolution PSF : FWHM 1.03 mm FWTM 2.50 mm 250 μm rod PSF FWHM FWTM

16. -16- 1st European Conference on Molecular Imaging Technology 9-12 May 2006 9-12 May 2006 Spatial Resolution G. T. Barnes, M. V. Yester, M. A. King, Optimizing computed tomography (CT) scanner geometry, SPIE Vol. 173 Application of Optical Instrumentation in Medicine VII (1979) MTF 10% sys exp = 0.71 lp/mm MTF

17. -17- 1st European Conference on Molecular Imaging Technology 9-12 May 2006 9-12 May 2006 Spatial Resolution MTF sys = MTF foc  MTF det  MTF sam  MTF alg G. T. Barnes, M. V. Yester, M. A. King, Optimizing computed tomography (CT) scanner geometry, SPIE Vol. 173 Application of Optical Instrumentation in Medicine VII (1979) MTF MTF 10% sys exp = 0.71 lp/mm a = 50  m

18. -18- 1st European Conference on Molecular Imaging Technology 9-12 May 2006 9-12 May 2006 Spatial Resolution MTF sys = MTF foc  MTF alg  MTF det  MTF sam G. T. Barnes, M. V. Yester, M. A. King, Optimizing computed tomography (CT) scanner geometry, SPIE Vol. 173 Application of Optical Instrumentation in Medicine VII (1979) MTF MTF 10% sys exp = 0.71 lp/mm

19. -19- 1st European Conference on Molecular Imaging Technology 9-12 May 2006 9-12 May 2006 Spatial Resolution MTF sys = MTF foc  MTF det  MTF sam  MTF alg G. T. Barnes, M. V. Yester, M. A. King, Optimizing computed tomography (CT) scanner geometry, SPIE Vol. 173 Application of Optical Instrumentation in Medicine VII (1979) MTF MTF 10% sys exp = 0.71 lp/mm

20. -20- 1st European Conference on Molecular Imaging Technology 9-12 May 2006 9-12 May 2006 Spatial Resolution MTF sys = MTF foc  MTF det  MTF sam  MTF alg G. T. Barnes, M. V. Yester, M. A. King, Optimizing computed tomography (CT) scanner geometry, SPIE Vol. 173 Application of Optical Instrumentation in Medicine VII (1979) MTF 10% sys theo = 0.73 lp/mm MTF MTF 10% sys exp = 0.71 lp/mm

21. -21- 1st European Conference on Molecular Imaging Technology 9-12 May 2006 9-12 May 2006 3.5 cm diameter cylinder filled with water Ring artifacts !!! 1 sec/projections Noise

22. -22- 1st European Conference on Molecular Imaging Technology 9-12 May 2006 9-12 May 2006 Biological Tissue HU Bone100 to 1000 Soft tissues0 to 80 Adipose tissues-50 to -100 Kidney30 Liver40 to 50 Blood40 σ ~ D -0.5 Noise GORE, J. C., TOFTS, P. S. Statistical limitations in computed tomography, Phys. Med. Biol., vol. 23, no. 6, pp. 1176-1182, 1978.

23. -23- 1st European Conference on Molecular Imaging Technology 9-12 May 2006 9-12 May 2006 Contrast phantom Average (HU) Standard deviation (HU) Density (g/cm 3 ) 1. Teflon 303.620.21.2 x 10 -3 2. Polyethylene -126.614.21.06 3. Polystyrene -86.618.20.93 4. Air hole -996.251.72.25 5. Polycarbonate 50.618.91.15 6. Nylon 55.516.31.2 Plexiglas 117.119.21.19 1 2 3 45 6 3.5 cm diameter Plexiglas phantom filled with 5 mm diameter rods Several tissue-like materials can be discriminated with sufficient accuracy. Measured dose (TLD): 0.7 mGy

24. -24- 1st European Conference on Molecular Imaging Technology 9-12 May 2006 9-12 May 2006 Conclusion detectcount APD-based inorganic scintillator detectors and fast digital multi-channel pulse processing electronics, as developed for the LabPET TM, are suitable to detect and count individual X- rays in the diagnostic energy range. Resolution : 1.03 mm Noise : 6.8 HU Dose : 0.7 mGy

25. -25- 1st European Conference on Molecular Imaging Technology 9-12 May 2006 9-12 May 2006 Future Work Higher resolution : magnification, higher sampling, smaller detector pixel size Image artefact : CT adapted image reconstruction algorithm Add more detector, more analog and digital electronics Objectives : ~ 1 μl PET resolution, < 500 μm CT resolution

26. -26- 1st European Conference on Molecular Imaging Technology 9-12 May 2006 9-12 May 2006 Acknowledgments Thanks to: Murray Davies and Henri Dautet of PerkinElmer Optoelectronics, Vaudreuil, QC for providing the detectors used in this study

27. -27- 1st European Conference on Molecular Imaging Technology 9-12 May 2006 9-12 May 2006 Thank You for your attention !