1. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 1 ClearPEM: a PET imaging system dedicated to breast cancer diagnostics J. Varela LIP/IST Lisbon & CERN EuroMedIm06, Marseille, May 2006

2. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 2 ClearPEM Project TAGUSPARK – Parque de Ciência e Tecnologia LIP - Laboratório de Instrumentação e Partículas Hospital Garcia Orta - Serviço Medicina Nuclear IBEB - Instituto Biofisica e Engenharia Biomédica IBILI - Instituto Biomédico de Investigação da Luz e Imagem INESC - Instituto de Engenharia de Sistemas e Computadores INEGI - Instituto de Engenharia Mecânica e Gestão Industrial Sensitivity@350 keV (%) central slice 4 cm off- axis 3 cm off- axis 2 cm off- axis 1 cm off- axis Y-axis (cm) X-axis (cm) The ClearPEM scanner is developed in the framework of the Crystal Clear Collaboration at CERN  Consortium PET-Mammography, Portugal  CERN, Geneva  VUB, Brussels

3. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 3 Good spatial resolution ( 2 mm, whole FoV)  Fine crystal segmentation (2x2 mm)  DoI measurement with adequate resolution (FWHM ~2 mm) High Sensitivity ( 0.05 cps/Bq, center FoV)  Solid angle coverage as large as possible  High photon interaction probability (20 mm long crystals)  High efficiency to Compton events in the detector (> 75%)  Minimize dead time in data acquisition (<10 % at highest rate) ClearPEM Requirements Low Random Background ( <25%, close to the chest)  Good time resolution (~ 1 ns)

4. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 4 ClearPEM Imaging System Breast and axilla exams  Breast exams with the patient in prone position  The plates rotate around the breast  PEM plates can be rotated for axilla exams PEM Robotic Device PEM Detector Plates

5. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 5 ClearPEM detector model ClearPEM Detector  6300 LYSO:Ce crystals  Avalanche photodiodes  Low noise electronics ClearPEM Detector:  Two detection plates  192 crystal matrices (8x4 crystals each)  Front-back APD readout for DoI measurement Optical simulation Plate surface 14x16 cm2

6. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 6 Crystals Quality Control  Production of 6300 crystal pixels concluded  Measurements with miniACOS (CERN):  700 crystals measured  Light yield dispersion (~12% rms) Light Yield 2x2x20mm depolished Energy resolution miniACOS LYSO:Ce Crystals 2 x 2 x 20 mm 3

7. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 7 Quality Control of APD Arrays 400 APD-arrays S8550-01 (Hamamatsu) Quality Control:  Bias voltage for M=50, 100, 200  Id/M per subarray  dM/dV (%/V)  Relative gain of individual pixels S8550-01 APD arrays Gain variation per Volt Id (16 pixels) < 70 nA Dark Current (Id) APD Number Relative gain of APD Pixels  = 4.6% dM/dV<4%/V

8. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 8 Performance of Detector Modules LYSO/BaSO 4 Matrix Measurements of 24 Detector Modules Quality Control:  Gain uniformity  Energy resolution  DoI resolution  Cross-talk See also poster P3_212 “Long-term stability of Clear-PEM Detector Modules”, C. Ortigão et al.

9. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 9 Gain Uniformity & Energy Resolution  Flood irradiation Cs-137  Measurement of relative gain of Detector Module pixels  Energy resolution at 662 keV  Results for 24 Detector Modules Relative Pixel Gain Average = 13.4% Energy Resolution RMS = 12.9%

10. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 10 Depth of Interaction Each asymmetry peak corresponds to irradiation at one beam location DoI Resolution for 32 pixels of one Detector Module FWHM ~ 2 mm A=(T-B)/(T+B) Crystal Collimated beam + 7 mm TopBottom

11. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 11 Top-Bottom Asymmetry  Flood irradiation Cs-137  Measurement of the width of the asymmetry distribution Asymmetry A=(T-B)/(T+B) Quality Control of 24 Modules

12. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 12 Cross-Talk Method: Select photopeak events in one crystal and study energy deposit in neighbor crystals Average crosstalk: 2 - 3 % 24 modules measured 1056 walls Average cross-talk per Module Na22 “flood” Red – select 511 keV Green – select 1274 keV

13. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 13 Single photon time resolution 2.1 ns (RMS) Time Resolution Non-optimized electronics (peaking time ~150 ns) Sampling ADC 10 bits 100 MHz Time difference APD(top) – APD (bottom) Preliminary

14. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 14 Full System Simulation  Monte – Carlo Simulations using GEANT4  NCAT phantom  Standardized uptake values one hour after the injection of 370 MBq.  Concentration of 2.1 kBq/cc for the soft tissue.  Detailed detector geometry  Includes trigger and data acquisition simulation ClearPEM Simulation Framework

15. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 15 Counting Rates Simulation setup Breast size Detector heads separation True rate Scatter fraction Randoms / Trues Asmall15 cm2.5 kHz30% 44% (no shield) 28% (Pb shield) Bmedium13 cm11.0 kHz30% 25% (no shield) 20% (Pb shield) C medium compressed 10 cm16.5 kHz30% 24% (no shield) 19% (Pb shield) BCA Single rate per Detector Head ~ 2.2 MHz (E  >50 keV) Fraction of Random Coincidences < 30% Standard uptakes for FDG injection of 370 MBq; Breast uptake 2.1 KBq/mL

16. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 16 DAQ/Trigger Performance DAQ and Trigger Efficiency: - above 90% for E>200 keV Time Resolution - single photon rms ~1.5 ns - photostatistics contributes ~1 ns - electronic noise ~1000 e-

17. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 17 “Full simulation” sensitivity image (uniform activity in the FoV) Sensitivity pattern: irregular variation Packing fraction: 52% FOV dimension: 16.2 x 14.5 cm 2 Transverse view Coronal view Sagittal view Coronal view sequence Monte Carlo Sensitivity Image

18. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 18 Reconstruction Performance Scanner rotation axis NCAT Breast Phantom Chain Phantom Scanner rotation axis Performance evaluation in optimal imaging conditions Performance evaluation in realistic imaging conditions Using Monte Carlo Simulated Data Detector Plates in 2 orthogonal orientations

19. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 19 Point Source Reconstruction Chain phantom 10 mm between point sources; No background activity.

20. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 20 Lesion Reconstructed Images lesion : background activity concentration 1:131:101:51:4 10 mm Ø lesion 5 mm Ø lesion 7 mm Ø lesion 3 mm Ø lesion lesion : background activity concentration 1:131:101:51:4 lesion : background activity concentration 1:131:101:51:4 lesion : background activity concentration 1:131:101:51:4 Poor visibillityGood visibillityNot visible (5 min total acquisition)

21. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 21 Coincidence digital trigger:  Digital algorithms (time and energy)  Time resolution ~ 1 ns  Good efficiency for multi-hit (Compton) events Fast Data Acquisition:  Data acquisition system able to cope with a single photon background rate of the order of 10 MHz  The data acquisition efficiency larger than 90%.  Pipeline structures for minimum dead time Data Acquisition Requirements

22. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 22 Architecture of Electronics Systems  Amplifier/ Multiplexer ASIC:  Sampling ADC (100 MHz)  Links LVDS  Crate 6U  4 DAQ boards  1 Trigger/DCC board  FPGAs 4 M gates Digital trigger Data reduction Data readout DAE crate PC Off-Detector 600 MHz Ampli AnalogMux 192:2 ADC 100 MHz 10 bit On-Detector Serializer Frontend Boards Service Boards Data Acquisition Electronics Frontend Boards Service Boards  APD Bias Voltage regulation  T, P monitoring  Power distribution

23. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 23 Frontend ASIC Technology AMS 0.35  m CMOS ASIC V1:  sampled-data memory, multiplexers, control logic OK  input amplifier with unstable bias levels Input: 192 channels Noise: ENC ~ 1000 e- Power per chip : < 2 mW/channel Clock frequency : 100 MHz Shaping: Peaking time 40 ns Analog memories: 10 samples Output multiplexing: 2 highest channels Frontend ASIC Specifications: ASIC V1 Layout

24. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 24 Layout of Test ASIC V2 Control Logic 4 channels multiplexers + buffers 5900  m 1600  m 4 channels Area – 9.44 mm 2 8 channels + switches + control logic + self-test

25. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 25 Detector Supermodule Frontend Electronics Integration Frontend Board Compact system inside the PEM Detector Head:  6000 APD channels  400 HV lines  160 high speed (600 MHz) output lines  High frequency clock (100 MHz)

26. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 26 Data Acquisition System DAQ module: - pipeline data storage - hit energy and time calculation Filter Module: - rejects out-of-time data - rejects high multiplicity events Trigger module: - performs coincidence trigger - random triggers - singles trigger DCC module: - collects relevant data - data transfer to PC

27. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 27 Processing Deserializers Control DAQ Board Trigger and Data Acquisition Boards DAQ Board tested successfully TRG/DCC Board TRG/DCC Board is under test Control Processing PCI Interface

28. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 28 Electromechanical safety switch Cable carrier Detector Heads Detector heads Adapter for source mounting Collision detection switches Water distribution block Patch Panel

29. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 29 Movements Robotic Device Movements Prototype Under Assembly

30. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 30 Conclusions The ClearPEM mammography scanner promises to have an interesting performance. Work is under way to conclude the prototype and to prove these expectations this year. Clinical tests are foreseen in 2007

31. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 31

32. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 32 Backup

33. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 33 Along axis parallel to plates Results with full simulation: Sensitivity at FOV center = 0.06 cps/Bq ClearPEM Sensitivity Along axis perpendicular to plates Plate separation 10 cm

34. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 34 + = True coincidence background (Geant4 full simulation) Random coincidence background (event generator) Investigate impact of random coincidences from outside the FOV in the quality of PEM images Events are mixed in the LMF file before image reconstruction Torso region 18% less contrast 5 mm Ø at 6 cm from CFOV Lesion uptake: 20.4 kBq/ml Breast uptake: 2.1 kBq/ml 2 orthogonal projections 300 s acquisition 3D-OSEM reconstruction Simulation approach Example: + = Effect of Randoms to PEM Images

35. ClearPEM, J. Varela EuroMedIm06, Marseille, May 2006 35 Breast configurationAxilla configuration Mechanical System