1. Andrei Nomerotski 1 Instrumentation for Medical Applications Andrei Nomerotski (Oxford Particle Physics) VC Forum, 17 November 2009

2. Andrei Nomerotski 2 Particle Detectors in Medicine  Energy scales of modern particle physics are much beyond needs of medicine but detection techniques are similar u High energy particles cascade to low energy particles  Detection of visible light and X-rays is in demand both in medical imaging and particle physics  Medical imaging u Slow rates (~Hz)  Modest # of frames per second u Complicated processing  Each frame is a lot of information u High data rates

3. Andrei Nomerotski 3 Driving Factors  Huge progress in micro (nano) electronics u New silicon technologies u New types of detectors u Complicated processing at sensor level  New materials  Computing  faster CPU u Taking advantage of Moore’s law u Software sophistication

4. Andrei Nomerotski 4 Outline  In the following will talk about u Positron Emission Tomography u Medical Imaging using silicon detectors u In Vivo Dosimetry

5. Andrei Nomerotski 5 Positron Emission Tomography (PET) 5 Cancer diagnostic tool Distinguish normal and cancerous tissue on the basis of their biological function

6. Andrei Nomerotski 6 FDG-PET: basic principle Two opposite PET detectors operating in coincidence 511 keV 511 keV  -ray 511 keV  -ray 18 F-fluoro-deoxy-glucose

7. Andrei Nomerotski 7 Whole Body PET  Usually combined with Computer Tomography (CT) u PET accuracy ~5 mm u Overlaid images give better accuracy u CT allow for attenuation corrections  2M scans annually u 20% per year growth

8. Andrei Nomerotski 8 Scintillator: Converts 511 keV gamma-rays into the light PMTs: Convert the scintillation light into a measurable electrical voltage pulse 511 keV gamma-rays 8 PET detector components

9. Andrei Nomerotski 9 Solid-State PET Detectors Avalanche photodiode (APD) High detection efficiency (~50%) Wide dynamic range Low gain (~100) Silicon Photomultiplier (SiPM) Work in Geiger mode Gain is comparable to PMTs (~10 6 ) High speed (similar to PMTs) Limited dynamic range Being considered Already developed

10. Andrei Nomerotski 10 Silicon Photomultiplier (SiPM) SiPM devicesSiPM microcells Schematic diagram 1mm x 1mm HAMAMATSU Inc. Geiger mode operated silicon arrays on a common substrate Invented in 90’s Last years – big improvements in parameters and available bareas

11. Andrei Nomerotski 11 Silicon Photomultiplier  Hamamatsu MPPC

12. Andrei Nomerotski 12 New Fast Scintillators  Promising new scintillators: PreLudeTM420 (LYSO) and BrilLanCeTM380 (LaBr3(Ce)) u By Saint-Gobain Cristaux et Detecteurs

13. Andrei Nomerotski 13 Time Of Flight PET  Use time information to localize interaction with ~few cm precision  Allows for better image quality for same dose u Or lower dose (=higher throughput) for same image quality  Need to achieve ~100 ps timing accuracy u Currently ~400 ps

14. Andrei Nomerotski 14 Combined PET & MRI  Difficult to combine due to strong magnetic field and high frequency interference  SiPMs work in strong magnetic field  PET scanner inside MRI scanner  Advantage over PET/CT - lower dose From S.Cherry, Advances in PET Imaging Technology

15. Andrei Nomerotski 15 PET R&D Activities in Oxford Physics  Ongoing R&D on SiPM  can be used for PET  Preparing a bid to Wellcome/STFC to build a TOF-PET demonstrator  Discussing common R&D projects with Churchill  Offer SiPM/TOF-PET MPhys project in Physics

16. Andrei Nomerotski 16 Medical Imaging

17. Andrei Nomerotski 17 Medical Imaging  Concentrate on X-ray imaging with silicon detectors  Nicely demonstrates advances in silicon industry u Not driven by science any more rather by telecommunications and PlayStation users  Nowadays use processes with 0.09  m = 90 nm min feature size with 45 nm in sight  Medipix – silicon pixel detector with integrated electronics and readout u Started at CERN in 90’s as by-product of R&D for future LHC experiments u Very successful with dozens of applications outside of PP (and medicine)

18. Andrei Nomerotski 18 X-Rays in Silicon  Visible photon range few  m  20keV X-ray range 5  m  100 keV X-ray range 80  m  For larger energies need different materials (higher Z)

19. Andrei Nomerotski 19 Hybrid-Pixel Detectors Pulse processing electronics provides simultaneously fast and noise free images

20. Andrei Nomerotski 20 Medipix2 Bump Bonding

21. Andrei Nomerotski 21 Charge sensitive preamplifier with individual leakage current compensation 2 discriminators with globally adjustable threshold 3-bit local fine tuning of the threshold per discriminator 1 test and 1 mask bit External shutter activates the counter 13-bit counter 1 Overflow bit Signal ~ few 1000 electrons (!) Medipix2 Pixel Cell Schematic

22. Andrei Nomerotski 22 Medipix2 Cell Layout

23. Andrei Nomerotski 23 Medipix2 Chip Architecture 256 x 256 pixels 5ms readout time (serial @ 200MHz) 300  s readout time (parallel @ 100MHz)

24. Andrei Nomerotski 24 Medipix Data Acquisition  Max frame rates ~ 1 kHz  USB interface- easy to use X-ray detector Medipix with USB interface

25. Andrei Nomerotski 25 Sample Images

26. Andrei Nomerotski 26 High resolution X-ray imaging using a micro- focus X-ray source Needle holding the sample Edges are enhanced by phase contrast effect S. Pospisil, J. Jakubek and co-workers, IEAP, CTU, Prague, CZ

27. Andrei Nomerotski 27 Future Trends  Microelectronics becomes more and more complex u Intelligence at pixel level  Medipix3 introduce corrections to amplitude to improve amplitude resolution

28. Andrei Nomerotski 28 Charge summing and allocation concept 55µm The winner takes all

29. Andrei Nomerotski 29 Medipix3 Simulation  Much improved amplitude resolution  Immune to threshold variations

30. Andrei Nomerotski 30 Material Reconstruction in CT Photon counting at 8 keV threshold water / non iodine iodine Brightness = density of materials (g/cm 3 )  Measurements in collaboration with the University of Canterbury, Christchurch G. Anton, T. Michel and co-workers, Univ. Erlangen, D  Amplitude information important to distinguish between different materials

31. Andrei Nomerotski 31 In Vivo Dosimetry  A lot of interest given JAI activities on therapy of cancer using particle accelerators  TLD, diodes, MOSFETs u TLDs are complicated to process u Diodes need a cable and continuous readout  New: MOSFET u Metal Oxide Semiconductor Field Effect Transistors u Absorbed dose change characteristics of MOSFET u Compact ~1 mm  Much needed instrument with a lot of room for improvement and new ideas scanditronix-wellhofer.com

32. Andrei Nomerotski 32 Medipix Activities in Oxford Area  Several Medipix/Timepix users u Diamond Light Source for crystal diffraction studies u Oxford Chemistry/Physics for Ion Imaging Mass Spectrometry u Oxford Engineering for Mammography  Talking to each other, may think about joining the Medipix collaboration

33. Andrei Nomerotski 33 Future: Monolithic Sensors  Future trend is in integration of detector and electronics in one sensor, MAPS (Monolithic Active Pixel Sensor)

34. Andrei Nomerotski 34 Monolithic Sensors with 3D Integration  Technologies becoming available to thin silicon wafers to 10 microns and to bond them together  New approach to monolithic sensors: 3D integration  Precision 1  m alignment u Interconnection of wafers by metal vias

35. Andrei Nomerotski 35 Ultra Thin Devices  First attempts to produce ultra-thin devices in industry and for particle detection are under way  hopefully will make its way to medical applications as well

36. Andrei Nomerotski 36 Summary  Enormous progress in detector technologies and nanoelectronics which can be applied to medical applications u Especially to imaging  A lot of interest from Physics side to apply better detectors to medicine  Medical applications are driven by practical needs and economics  benefit from communications between two communities Acknowledgements: Medipix collaboration