AQUA A DVANCED QU ALITY A SSURANCE FOR CNAO

1. AQUAADVANCED QUALITY ASSURANCE FOR CNAO 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)

2. 1 2 3 CNAO (CENTRO NAZIONALE DI ADROTERAPIA ONCOLOGICA) 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. IVI Interaction Vertex Imaging In-beam PET Crystals Resistive Plate Chambers PRR Proton Range Radiography NST Nuclear Scattering Tomography AQUA PROGRAMS FOR CNAO

4. E ER E L PRR: PROTON RANGE RADIOGRAPHY 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: Range resolution due to straggling (S) and beam momentum spread (P) K.M. Hanson et al, Phys. Med. Biol. 26 (1981) 965 The residual energy is commonly measured with a monolithic crystal scintillator. Alternative system use of a plastic scintillator stacks. P. Pemler et al, Nucl. Instr. and Meth. A432(1999)483

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

6. 50 100 150 200 MeV 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: Range straggling ~ 1.5 % rms

7. 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: AN : signal in last slice N AN-1 : signal in slice N-1 T: slice thickness

8. electromagnetic only Electromagnetic nuclear+electromagnetic Nuclear 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: The expected range-energy correlation can be exploited to discard nuclear interaction events:

9. PRR RESOLUTION STUDY 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: In collaboration with Prof. George Chen Massachusetts General Hospital (Boston) GOALS: Treatment plan verification Organ motion correction

10. SCINTILLATOR RANGE TELESCOPE 30 scintillators 3 mm thick, 10x10 cm2, read-out with wavelength shifter fibres and solid state sensors • 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 mm2 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) ~ 16 photoelectrons

11. 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. TRACKING DETECTORS FOR PRR • 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/cm2 • Radiation resistance above 1014 particles/cm2 • Low mass ~ 0.5% X0 per 2-D detector (0.3 mm H2O • TIME-STAMPED EVENTS F. Sauli, Nucl. Instr. and Meth. A386(1997)531 GEM chamber, 10x10 cm2 active Fast digital readout Completion, test and calibration: fall ‘08 Installation at CNAO: spring ‘09

13. GEM DETECTORS GAS ELECTRON MULTIPLIER 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: Typical geometry: 5 µm Cu on 50 µm Kapton 70 µm holes at 140 mm pitch 5-10,000 INDEPENDENT PROPORTIONAL COUNTERS per cm2 F. Sauli, Nucl. Instrum. Methods A386(1997)531

14. DRIFT GAIN INDUCTION 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

15. RATE CAPABILITY: 3.106 particles mm-2 65 µm rms ~ 4 1014 particles cm-2 GEM PERFORMANCES 2-D POSITION ACCURACY: S. Bachmann et al, Nucl. Instr. and Meth. A479(2002)294 LONG-TERM RADIATION RESISTANCE: M. Alfonsi et al, NIMA518(2004)106

16. Honeycomb plates GEM foils 2-D Readout board COMPASS TRIPLE GEM Sturdy, light construction used for the tracker of the COMPASS experiment at CERN. 30x30 cm2 active, 2-dimensional electronic readout 22 detectors are operational since 2002 in high intensity beam. C. Altumbas et al, Nucl. Instrum. Methods A490(2002)177

17. GEM DETECTORS Can be built in a variety of shapes, including non-planar HALF-MOON TRIPLE GEM(TOTEM) 40 detectors in installation at CERN LHC 10-Chambers telescope:

18. GEM DETECTORS Two sectored GEM foils, 60 cm long (Gas Detectors Development at CERN) CYLINDRICAL Prototype for NA49 upgrade 60 cm

19. INTERACTION VERTEX IMAGING (IVI) SETUP 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 In collaboration with A. Scribano (Siena University)

20. Primary Secondary Total Secondary INTERACTION VERTEX IMAGING - SIMULATIONS Simulation of primary interactions for 400 MeV/u 12C 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. The drop-off slope of the distribution provides information on the Bragg spectrum; it should be studied experimentally. P. Solevi, Study of an in-beam PET system for CNAO. PhD Thesis at the University of Milano (2007)

21. INTERACTION VERTEX IMAGING EFFECT OF TRACK ENERGY AND ANGLE SELECTION E>100 MeV, cosθ<0.9 Correlation plots between real and reconstructed vertex Along the beam: Perpendicular to the beam:

22. Elastic: 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. p The method was developed 25 years ago by G. Charpak and collaborators. J.C. Duchazeaubeneix et al, J. Comp. Assisted Tomography 4 (1980)803

23. NUCLEAR SCATTERING TOMOGRAPHY 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 cm3 10 mm3voxels --> 105 voxels. For 5% statistical accuracy on local density (500 events/voxel) ~5.104 events/cm3 Scattering probability ~ 10-3 cm-1 Total beam flux ~ 108 cm-2 Total number of events ~ 5.107 Total acquisition (at 1 MHz) ~ 1 min Total dose ~ 30 mGy Requires the development of very fast (> 1 MHz) data acquisition electronics.

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

25. D Y X IN-BEAM PET (CRYSTALS) Preliminary study of localization and Depth of Interaction determination using segmented crystals and a multi-anode photomultiplier 5 LYSO crystals 60x30x12 mm3 PHOTONIS XP85013 Micro-Channel Photomultiplier (MCP) 8x8 anode pads Signal risetime/width: 0.6/1.8 ns The center of gravity of the signal distribution provides the X-Y coordinates, the width the DOI

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

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

28. SiPM Developed by various laboratories and commercially available Hamamatsu MPPC: 1x1 mm2 Possible detector assembly: array of independent fingers Position-sensitive array: 3x3 mm3 6x6 mm2 array MAJOR OPEN ISSUES:Light collection efficiency? Saturation? Intrinsic time resolution (crystal+sensor+electronics)? Radiation resistance? Cost?

29. 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: Time resolution vs overvoltage for MIPs: The best resolution are obtained with high pressures (10 bar) and narrow gaps (100 µm): Yu.Pestov, Nucl. Instr. and Meth. 196(1982)45

30. MULTIGAP RESISTIVE PLATE CHAMBER (RPC) 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 E. Cerron Zeballos et al, Nucl. Instr. and Meth. A 374(1996)132

31. ~ 7.5 m ~ 4 m MULTIGAP RPC TIME OF FLIGHT FOR ALICE RPC strip, ~120x12 cm2 Adopted for the Time of Flight detector of ALICE: large area, very good time resolution (~50 ps rms) The ALICE Experiment at CERN LHC J. of Instrum. JINST 3 S08002 (2008)

32. IN-BEAM PET WITH RESISTIVE PLATE CHAMBERS Multi-layer thin-gap RPC: the resistive electrode act as converters for photons: Development at Coimbra University (P. Fonte) 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 M. Couceiro et al, Nucl. Instr. and Meth. A580(2007)915

33. 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. • 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 • ...... In collaboration with T. Tabarelli (Univ. La Bicocca, Milano).

34. beam intensity should be reduced by four orders data acquisition rate could be increased 10x PRESENT PERFORMANCES PRR: Pixel size 10 mm2 --> 103 pixels for 10x10 cm2 image For 3% statistical error (103 events/pixel) ~ 106 tracks --> 10 s for 100 kHz readout NST: Voxel size 5x5x5 mm3 --> 2.5 104 voxels for 10x10x30 cm3 target For 3% statistical error (103 events/voxel) --> 2.5 107 events --> 250 s (~4 min) for 100 kHz readout Estimated do not include efficiency losses, data analysis time etc. RATES AND EXPOSURE TIME Therapeutic beam intensity ~ 1010 p/s on ~1cm2 Raster beam scan: partly overlapping spots moved every 5 ms (~5.107 p/spot) PRESENT DETECTORS LIMITATION: GEM Tracker: 107 p/cm2 (intrinsic due to space charge) Multi-events resolving time (charge collection+electronics shaping) ~100 ns Total flux over 10x10 cm2 for 10% pileup ~ 106 p/s ---> 1 MHz Electronics readout ~ 100 kHz (105 p/s) RANGE TELESCOPE: Intrinsic (scintillator+WLS decay time) ~ 30 ns Silicon PM+shaping ~ 100 ns --> 10 MHz Electronics readout ~ 100 kHz BETTER RESOLUTION-SHORTER ACQUISITION TIMES: 100 kHz--> >1 MHz