1. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 0 AQUA A DVANCED QU ALITY A SSURANCE FOR CNAO U. Amaldi, S. Iliescu, N. Malakhov, J. Samarati, F. Sauli and D. Watts TERA Foundation and CERN Presented by Fabio Sauli U. Amaldi, S. Iliescu, N. Malakhov, J. Samarati, F. Sauli and D. Watts TERA Foundation and CERN Presented by Fabio Sauli Advanced Instrumentation for Cancer Diagnosis and Treatment ESF workshop (Oxford 23-26 September 2008) Advanced Instrumentation for Cancer Diagnosis and Treatment ESF workshop (Oxford 23-26 September 2008)

2. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 1 CNAO (CENTRO NAZIONALE DI ADROTERAPIA ONCOLOGICA) 1 3 2 NATIONAL CENTRE OF ONCOLOGICAL HADROTHERAPY (Pavia, Italy) Synchrotron accelerator for light ions (protons, carbon) up to 400 MeV/u 3 fixed beam treatment rooms, 2 gantries Startup in spring 2009 Status of the accelerator (March “08):

3. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 2 AQUA PROGRAMS FOR CNAO In-beam PET Crystals Resistive Plate Chambers PRR Proton Range Radiography IVI Interaction Vertex Imaging NST Nuclear Scattering Tomography

4. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 3 PRR: PROTON RANGE RADIOGRAPHY K.M. Hanson et al, Phys. Med. Biol. 26 (1981) 965 P. Pemler et al, Nucl. Instr. and Meth. A432(1999)483 For beam energies above total absorption in the target, a correlated measurement of track position and residual energy allows to reconstruct the integrated density image: The residual energy is commonly measured with a monolithic crystal scintillator. Alternative system use of a plastic scintillator stacks. EE EERER L Range resolution due to straggling (  S ) and beam momentum spread (  P )

5. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 4 PROTON RANGE TELESCOPE Tracker Gas Electron Multiplier (GEM) detectors Digital Strip Readout Range/Energy loss Plastic scintillator Stack Silicon Photomultipliers Readout Measurement of range and energy loss High intrinsic rate capability (>1 MHz) Density 1, (almost) tissue equivalent Low cost, easily scalable to larger sizes Using modern technology developed for High Energy Physics Light, 2-dimensional readout High rate (> 1 MHz) Radiation resistant Large areas at low cost

6. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 5 GEANT 4 SIMULATIONS Mean differential energy loss in 3 mm thick scintillator slices and projected range as a function of initial energy (50 to 200 MeV in 25 MeV steps: 50 100 150 200 MeV Range straggling ~ 1.5 % rms

7. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 6 RANGE DETERMINATION Due to straggling, two events with the same initial energy have a different energy loss profile, depending on penetration in the last scintillator slice: A simple algorithm, the fraction of energy loss in the last scintillator to the one before the last, allows to deduce the fractional penetration in the last slice: A N : signal in last slice N A N-1 : signal in slice N-1 T: slice thickness

8. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 7 ENERGY LOSS: ELECTROMAGNETIC VS NUCLEAR A fraction of events (~25%) undergo a nuclear interaction. The residual range for a given initial energy has a long tail at short values: electromagnetic only nuclear+electromagnetic Electromagnetic Nuclear The expected range-energy correlation can be exploited to discard nuclear interaction events:

9. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 8 PRR RESOLUTION STUDY In collaboration with Prof. George Chen Massachusetts General Hospital (Boston) Simulated Proton Range Radiography, deduced from conventional CAT scans: Difference between the initial range map and the subsequent map generated from the initial planning CT scan and the follow-up scan after 5 weeks of treatment: GOALS: Treatment plan verification Organ motion correction

10. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 9 SCINTILLATOR RANGE TELESCOPE 30 scintillators 3 mm thick, 10x10 cm 2, read-out with wavelength shifter fibres and solid state sensors ~ 16 photoelectrons Fast scintillator: BC-408 Rise/decay time 0.9/2.1 ns Peak emission 425 nm WLS: BC-482A 1mm Decay time 12 ns Absorption peak 420 nm Emission peak 494 nm MMPC: Hamamatsu S-10362-11-050U 1 mm 2 active, 400 pixels Quantum efficiency 40% at 500 nm Time resolution 200-300 ps Response to minimum ionizing electrons (protons are from 3 to 20 times MIPs)

11. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 10 SCINTILLATOR RANGE TELESCOPE The scintillator modules are mounted on a frame support; the space between counters permits the insertion of absorbers to extend the residual energy range. Two scintillators back to back with readout electronics:

12. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 11 TRACKING DETECTORS FOR PRR F. Sauli, Nucl. Instr. and Meth. A386(1997)531 GEM: GAS ELECTRON MULTIPLIERS Fast gaseous position-sensitive detector, used in HEP experiments. The ionization released in a thin gas layer by charged particles is amplified and detected on perpendicular readout strips. Typical performances: Single particle detection and recording Position accuracy ~ 100 µm Rate capability > 1 MHz/cm 2 Radiation resistance above 10 14 particles/cm 2 Low mass ~ 0.5% X 0 per 2-D detector (0.3 mm H 2 O TIME-STAMPED EVENTS GEM chamber, 10x10 cm 2 active Fast digital readout Completion, test and calibration: fall ‘08 Installation at CNAO: spring ‘09

13. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 12 GEM DETECTORS GAS ELECTRON MULTIPLIER Typical geometry: 5 µm Cu on 50 µm Kapton 70 µm holes at 140 mm pitch F. Sauli, Nucl. Instrum. Methods A386(1997)531 Thin, metal-coated polymer foil with high density of holes. On application of a voltage difference, each hole acts as an individual proportional counter, multiplying the electrons entering from the drift region. The amplified electrons leave the hole; most of the ions are collected by the upper electrode: 5-10,000 INDEPENDENT PROPORTIONAL COUNTERS per cm 2

14. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 13 MULTIGEM DETECTORS GEM electrodes can be cascaded, injecting the electrons released in one into the next multiplier; cascades of up to five GEMs have been tested. This allows to obtain larger gains, or safer operating conditions for the same gain. The track coordinates are obtained from the charge collected on strips or pads: S. Bachmann et al, Nucl. Instr. and Meth. A479 (2002) 294 DRIFT INDUCTION GAIN

15. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 14 GEM PERFORMANCES 65 µm rms 2-D POSITION ACCURACY: M. Alfonsi et al, NIMA518(2004)106 LONG-TERM RADIATION RESISTANCE: ~ 4 10 14 particles cm -2 3.10 6 particles mm -2 RATE CAPABILITY: S. Bachmann et al, Nucl. Instr. and Meth. A479(2002)294

16. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 15 COMPASS TRIPLE GEM Honeycomb plates GEM foils 2-D Readout board C. Altumbas et al, Nucl. Instrum. Methods A490(2002)177 Sturdy, light construction used for the tracker of the COMPASS experiment at CERN. 30x30 cm 2 active, 2-dimensional electronic readout 22 detectors are operational since 2002 in high intensity beam.

17. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 16 GEM DETECTORS HALF-MOON TRIPLE GEM(TOTEM) 40 detectors in installation at CERN LHC Can be built in a variety of shapes, including non-planar 10-Chambers telescope:

18. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 17 GEM DETECTORS CYLINDRICAL Prototype for NA49 upgrade Two sectored GEM foils, 60 cm long (Gas Detectors Development at CERN) 60 cm

19. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 18 INTERACTION VERTEX IMAGING (IVI) SETUP In collaboration with A. Scribano (Siena University) Large angle Single-arm charged particle detectors: GEM detectors with fast electronic readout. Active during therapeutic exposures: the incoming beam has known position but cannot be detected

20. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 19 INTERACTION VERTEX IMAGING - SIMULATIONS Simulation of primary interactions for 400 MeV/u 12 C beam show a large yield of charged prongs (mostly protons) emitted along the trajectory; this can be exploited for in-beam dose monitoring. There is however a large halo given by secondary vertices, mostly in the forward direction. PrimarySecondary P. Solevi, Study of an in-beam PET system for CNAO. PhD Thesis at the University of Milano (2007) Total Secondary The drop-off slope of the distribution provides information on the Bragg spectrum; it should be studied experimentally.

21. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 20 INTERACTION VERTEX IMAGING Correlation plots between real and reconstructed vertex EFFECT OF TRACK ENERGY AND ANGLE SELECTION E>100 MeV, cosθ<0.9 Along the beam: Perpendicular to the beam:

22. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 21 NUCLEAR SCATTERING TOMOGRAPHY (NST) At high proton energy (~600 MeV), recording of the protons scattered by the target and reconstruction of the interaction vertex provides the 3-Dimensional density distribution. From the subset of elastic proton-proton scattering, one gets the hydrogen density distribution. Elastic: The method was developed 25 years ago by G. Charpak and collaborators. J.C. Duchazeaubeneix et al, J. Comp. Assisted Tomography 4 (1980)803 p

23. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 22 NUCLEAR SCATTERING TOMOGRAPHY Requires the development of very fast (> 1 MHz) data acquisition electronics. The p-p cross section has a maximum at 1200 GeV/c (~ 600 MeV); about 50% of the interactions are elastic. Elastic events are selected from 2- tracks data using angular correlation and coplanarity. Target volume of 10x10x10 cm 3 10 mm 3 voxels --> 10 5 voxels. For 5% statistical accuracy on local density (500 events/voxel) ~5.10 4 events/cm 3 Scattering probability ~ 10 -3 cm -1 Total beam flux ~ 10 8 cm -2 Total number of events ~ 5.10 7 Total acquisition (at 1 MHz) ~ 1 min Total dose ~ 30 mGy

24. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 23 IN-BEAM PET Computed distribution of  + emitters 212 MeV/u and 343 MeV/u 12 C beam: Imaging of co-linear gammas from positrons emitted by isotopes produced by the 12 C -target interactions: 11 C, 10 C, 15 O Dual-head scanner: P. Solevi, Study of an in-beam PET system for CNAO. PhD Thesis at the University of Milano (2007)

25. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 24 IN-BEAM PET (CRYSTALS) PHOTONIS XP85013 Micro-Channel Photomultiplier (MCP) 8x8 anode pads Signal risetime/width: 0.6/1.8 ns Preliminary study of localization and Depth of Interaction determination using segmented crystals and a multi-anode photomultiplier 5 LYSO crystals 60x30x12 mm 3 The center of gravity of the signal distribution provides the X-Y coordinates, the width the DOI X D Y

26. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 25 IN-BEAM PET (CRYSTALS) Width: Depth of interaction Real Measured ~ 1.5 mm rms D:3 mm 12 mm 25 mm Center of Gravity: Localization in the plane of the MCP MCP 22 Na Coincidence Preliminary measurements with a collimated 22 Na source With a simple algorithm, one can obtain a DOI determination corresponding to ~ 1/3 of the crystal thickness.

27. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 26 TIME OF FLIGHT PET (TOF) WITH SOLID STATE SENSORS Single photoelectron time resolution as a function of voltage: G. Collazuol et al, Nucl. Instr. and Meth. A581(2007)461 Array of individual Avalanche Photodiodes, operated in the Geiger mode: Single photon counting, very good time resolution SILICON PHOTOMULTIPLIER (SiPM) GEIGER AVALANCHE PHOTODIODE (G-APD) MULTI-PIXEL PHOTON COUNTERS (MPPC)

28. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 27 SiPM Developed by various laboratories and commercially available 1x1 mm 2 3x3 mm 3 6x6 mm 2 array Possible detector assembly: array of independent fingers Position-sensitive array: MAJOR OPEN ISSUES: Light collection efficiency? Saturation? Intrinsic time resolution (crystal+sensor+electronics)? Radiation resistance? Cost? Hamamatsu MPPC:

29. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 28 TOF PET: RESISTIVE PLATE CHAMBERS Parallel plate gaseous avalanche chambers have excellent time resolution for charged particles. The use of resistive electrodes limits the dead time after a discharge: Yu.Pestov, Nucl. Instr. and Meth. 196(1982)45 The best resolution are obtained with high pressures (10 bar) and narrow gaps (100 µm): Time resolution vs overvoltage for MIPs:

30. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 29 MULTIGAP RESISTIVE PLATE CHAMBER (RPC) E. Cerron Zeballos et al, Nucl. Instr. and Meth. A 374(1996)132 A stack of thin RPC gaps provides good efficiency and time resolution at atmospheric pressures; only one HV used, with floating middle plates. The signal is detected on external pickup electrodes. 10 gap, double stack module (ALICE) Efficiency and time resolution for fast charged particles:  ~96%  ~50 ps

31. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 30 MULTIGAP RPC TIME OF FLIGHT FOR ALICE Adopted for the Time of Flight detector of ALICE: large area, very good time resolution (~50 ps rms) RPC strip, ~120x12 cm 2 ~ 4 m ~ 7.5 m The ALICE Experiment at CERN LHC J. of Instrum. JINST 3 S08002 (2008)

32. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 31 IN-BEAM PET WITH RESISTIVE PLATE CHAMBERS Efficiency for 511 keV  as a function of layers (lead glass converters): ADVANTAGES: TOF (~ 50 ps) Large areas at low cost -> Full body PET Arbitrary read-out pattern (strips, pads...) DOI (thin modules) DRAWBACK: No energy resolution Multi-layer thin-gap RPC: the resistive electrode act as converters for photons: M. Couceiro et al, Nucl. Instr. and Meth. A580(2007)915 Development at Coimbra University (P. Fonte)

33. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 32 AQUA RPC-PET DEVELOPMENT Development of a prototype multi-gap RPC with thin (300 µm) glass converter plates. To improve stability of operation, the glass is coated with a high-resistivity diamond-like layer. Thin nylon wires (fishing lines) maintain the gaps. The stack is filled with the operating gas mixture and sealed; the 2-D readout electrodes are external to the stack. In collaboration with T. Tabarelli (Univ. La Bicocca, Milano). OPEN QUESTIONS: Efficiency: choice of best electrodes (must be dielectric) Time and space resolution Tolerance to other radiations (neutrons, protons) Gas choice, Long-term behaviour......

34. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 33 RATES AND EXPOSURE TIME Therapeutic beam intensity ~ 10 10 p/s on ~1cm 2 Raster beam scan: partly overlapping spots moved every 5 ms (~5.10 7 p/spot) PRESENT DETECTORS LIMITATION: GEM Tracker: 10 7 p/cm 2 (intrinsic due to space charge) Multi-events resolving time (charge collection+electronics shaping) ~100 ns Total flux over 10x10 cm 2 for 10% pileup ~ 10 6 p/s ---> 1 MHz Electronics readout ~ 100 kHz (10 5 p/s) RANGE TELESCOPE: Intrinsic (scintillator+WLS decay time) ~ 30 ns Silicon PM+shaping ~ 100 ns --> 10 MHz Electronics readout ~ 100 kHz PRESENT PERFORMANCES PRR: Pixel size 10 mm 2 --> 10 3 pixels for 10x10 cm 2 image For 3% statistical error (10 3 events/pixel) ~ 10 6 tracks --> 10 s for 100 kHz readout NST: Voxel size 5x5x5 mm 3 --> 2.5 10 4 voxels for 10x10x30 cm 3 target For 3% statistical error (10 3 events/voxel) --> 2.5 10 7 events --> 250 s (~4 min) for 100 kHz readout Estimated do not include efficiency losses, data analysis time etc. beam intensity should be reduced by four orders data acquisition rate could be increased 10x BETTER RESOLUTION-SHORTER ACQUISITION TIMES: 100 kHz--> >1 MHz

35. F. Sauli - ICPT Workshop (Oxford, 23-26 September 2008) 34