1. P. Lecoq CERN 1 February 2012 ICTR-PHE 2012, Geneva, February 27-March 2, 2012 Novel multimodal endoscopic probes for simultaneous PET/ultrasound imaging for image-guided interventions FP7 project, call Health 2010 P. Lecoq CERN, Geneva, Switzerland On behalf of the EndoTOFPET-US collaboration "The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/ 2007-2013) under Grant Agreement n°256984."

2. P. Lecoq CERN 2 February 2012 ICTR-PHE 2012, Geneva, February 27-March 2, 2012 EndoTOFPET-US project Development of new biomarkers First clinical targets: pancreatic/prostatic cancer Tool: dual modality PET-US endoscopic probe –Spatial resolution: 1mm –Timing resolution: 200ps –High sensitivity to detect 1mm tumor in a few mn –Energy resolution: discriminate Compton events

3. P. Lecoq CERN 3 February 2012 ICTR-PHE 2012, Geneva, February 27-March 2, 2012 The consortium

4. P. Lecoq CERN 4 February 2012 ICTR-PHE 2012, Geneva, February 27-March 2, 2012 Technical challenges Non-conventional PET configuration –Assymetric: one PET head in near contact to ROI Simulation and reconstruction problems –Endoscopic: one PET head inside the body Miniaturization High background from other organs (heart, bladder,…) Variable geometry

5. P. Lecoq CERN 5 February 2012 ICTR-PHE 2012, Geneva, February 27-March 2, 2012 Technical challenges Innovative solutions –Very thin crystal pixels for the internal probe (  pulling-down crystal fibers production technology?) for high granularity of the internal probe and <1mm spatial resolution –TOF electronic collimation with < 200ps timing resolution for background rejection outside 3cm ROI –Digital light detection: SiPM with single SPAD readout for single optical photon counting and ultimate timing resolution –Diffractive optics light concentrators between crystals and SiPM for optimizing light collection –High level of electronics and mechanical integration (5  m precision) For miniaturization –Tracking of all movables parts for <1mm determination of their relative positions

6. P. Lecoq CERN 6 February 2012 ICTR-PHE 2012, Geneva, February 27-March 2, 2012 Anatomical constraints

7. P. Lecoq CERN 7 February 2012 ICTR-PHE 2012, Geneva, February 27-March 2, 2012 Geometry of PET Head

8. P. Lecoq CERN 8 February 2012 ICTR-PHE 2012, Geneva, February 27-March 2, 2012 20.5x20.5x1.5 cm 3 4096 LYSO crystals 3x3x15 mm 3 64 matrices of 64 crystals each Hamamatsu 50  m SiPM 8x8 matrix External Plate

9. P. Lecoq CERN 9 February 2012 ICTR-PHE 2012, Geneva, February 27-March 2, 2012 Endoscopic probe: crystals EM tracking sensor PET head US Probe with biopsy needle PROBE 9x18 LYSO or LSO:Ce, Ca matrix 0.75x0.75x10mm 3 crystals 80  m 3M ESR gap EXTERNAL PLATE 20.5x20.5 cm 2 LYSO:Ce matrix 3x3x15mm 3 crystals 80  m 3M ESR gap

10. P. Lecoq CERN 10 February 2012 ICTR-PHE 2012, Geneva, February 27-March 2, 2012 Crystal performance 16 LYSO crystals matrix 0.75x0.75x10mm 3 80  m 3M ESR wrapping Uniformly irradiated by a 137 Cs source DRY contact to PMT 2020Q ENDOSCOPIC PROBE 16 LYSO crystals matrix 3x3x15mm 3 80  m 3M ESR wrapping Uniformly irradiated by a 137 Cs source DRY contact to PMT 2020Q EXTERNAL PLATE

11. P. Lecoq CERN 11 February 2012 ICTR-PHE 2012, Geneva, February 27-March 2, 2012 Endoscopic probe: A new concept of fully digital SiPM EM tracking sensor PET head US Probe with biopsy needle 50um 30um 800um 16x26 SiPM-like or CLUSTER 48 TDCs per crystal 864 TDCs on the chip Considering also active quenching 14.4mm 7.2mm 9x18 IMAGER

12. P. Lecoq CERN 12 February 2012 ICTR-PHE 2012, Geneva, February 27-March 2, 2012 Measurements & Comparison ParameterEndoTOFPET-USPhilips # SPAD / cluster 4166400 Max. Fill Factor (%) 5077 PDP (% @ 430nm) 3231 Cluster Pitch (μm) 8004000 # clusters per chip 4x6 (9x18)2x2 # TDCs / cluster column 481 # TOAs / cluster 481 TDC resolution or LSB (ps) 51.8- Lost TOAs few many Clock (MHz) 25200 Max. Conv. rate (MS/s) 3-

13. P. Lecoq CERN 13 February 2012 ICTR-PHE 2012, Geneva, February 27-March 2, 2012 Optical coupling system Collimator Detector Lenticular lens Crystal Simulations predict a yield of 68-70% (gain of ~1.7) Fill factor of the photodetector (~41%)) 500  m thick light concentrator glued on the crystal & photodetctor

14. P. Lecoq CERN 14 February 2012 ICTR-PHE 2012, Geneva, February 27-March 2, 2012 Overview of readout architecture PCIe interface ASIC 1 16 4 ASIC 1 16 Frontend readout & control 1 SPAD 1 2 data clock, reset/sync, control DAQ Server Frontend readout & control Backend readout & control SPAD readout & control DETECTOR

15. P. Lecoq CERN 15 February 2012 ICTR-PHE 2012, Geneva, February 27-March 2, 2012 Event and DAQ rates  The hit rate in the external plate is expected to be 10 kHz per crystal. The total hit rate is 40 MHz.  The event rate in the internal probe is of the order of 1 MHz.  The total average data rate from the PET plate is 2 Gb/s. The available bandwidth is 3.2 Gb/s (4 x LVDS links at 800 Mb/s each)  The total average rate from the internal probe is of the order of 1 Gb/s. A total bandwidth of 1.6 Gb/s is available (2 x LVDS links at 800 Mb/s each)  Random coincidence rate is estimated at 250 kHz (assuming 6.25 ns coincidence window). The true coincidence rate is assumed to be of the same order. Therefore we assume that the total trigger rate is 0.5 MHz.  For a trigger rate of 0.5 MHz the storage rate is relatively modest (about 100 Mbyte/s).  The stored data is reduced by a factor 10 after offline filtering with a coincidence window of 600 ps.

16. P. Lecoq CERN 16 February 2012 ICTR-PHE 2012, Geneva, February 27-March 2, 2012 F. Powolny et al., IEEE Trans. Nucl. Sc., Vol 58, N°3, pp597-604, June 2011 FWHM in coincidence Hama 25  m FWHM in coincidence Hama 50  m FWHM in coincidence Hama 100  m Fill factor30.8%61.5%78.5% # pixels144003600900 Best settings73 V Bias 150mV Th 72.4 V Bias 100mV Th 70.3 V Bias 300mV Th 2 LSO PML 2x2x10mm 3 340ps220ps280ps 2 LSO co-doped Ce.Ca AGILE 2x2x10mm 3 170ps 2 LYSO Proteus 2x2x10mm 3 175ps 2 LYSO Proteus 0.75x0.75x10mm 3 188ps Can we achieve 200ps timing resolution? More data in: Auffray et al. Proceedings of the IEEE NSS/MIC conference, Valencia, Oct. 2011

17. P. Lecoq CERN 17 February 2012 ICTR-PHE 2012, Geneva, February 27-March 2, 2012 Project Organization WP1: UnivMed Project Coordination WP2: CERN Crystals and optics Scintillating fibers and diffrative coupling optics WP6: TUM Clinical requirements & preclinical and pilot clinical studies Feasibility tests on pigs, Pilot clinical tests, Impact on biomarker studies WP3: Delft TU Photodetectors Novel digital photodetectors WP4: LIP FE and DAQ electronics Highly integrated TOF electronics WP5: DESY Detector Integration Miniaturized probe Tracking&Image fusion 4 years project

18. P. Lecoq CERN 18 February 2012 ICTR-PHE 2012, Geneva, February 27-March 2, 2012Conclusion EndoTOFPET-US is an approved FP7 project running since 1 year Objectives –Develop a multimodal imaging/interventional endoscopic probe based on several technological breakthroughs –To be used a a tool to develop biomarkers in priority for pancreas and prostate –Define a roadmap for the development of a new generation of multimodal endoscopic probes for different clinical applications "The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/ 2007-2013) under Grant Agreement n°256984."

19. P. Lecoq CERN 19 February 2012 ICTR-PHE 2012, Geneva, February 27-March 2, 2012 Backup slides

20. P. Lecoq CERN 20 February 2012 ICTR-PHE 2012, Geneva, February 27-March 2, 2012

21. P. Lecoq CERN 21 February 2012 ICTR-PHE 2012, Geneva, February 27-March 2, 2012 Diffractive Optics Sensitive Strips pads TDC Array Dead Space (compensated by concentrators) 9 x 18 clusters

22. P. Lecoq CERN 22 February 2012 ICTR-PHE 2012, Geneva, February 27-March 2, 2012 Optimization LSO vs LSO 2x2x10mm 3 SiPM Hamamatsu 50  m

23. P. Lecoq CERN 23 February 2012 ICTR-PHE 2012, Geneva, February 27-March 2, 2012 Reproducibility LSO vs LSO SiPM Hamamatsu 50  m

24. P. Lecoq CERN 24 February 2012 ICTR-PHE 2012, Geneva, February 27-March 2, 2012 24 System properties  System clock (160 MHz), sync and reset signals distributed to all frontends  Data transmission to DAQ: serial encoded 8/10B  DAQ server PCIe interface used for data and frontend configuration  Data are organized in Data Frames: time window of 6.4  s (1024 clocks)  Time tag of data hits: frame counter, coarse counter, fine counter  Clock counters in the detectors are synchronized with the sync signal  Coincidence trigger and data re-formatting in backend  Data from coincidence events are stored in the DAQ server

25. P. Lecoq CERN 25 February 2012 ICTR-PHE 2012, Geneva, February 27-March 2, 2012 Can we achieve 200ps timing resolution? 2 LSO co-doped Ce.Ca AGILE 2x2x10mm 3 2 LYSO Proteus 2x2x10mm 3 2 LYSO Proteus 0.75x0.75x10mm 3