1. The PRIMA Project : development of a proton Computed Tomography system Mara Bruzzi Consuntivo PRIMA+ -CSN5 2 Maggio 2013 Roma 1 M. Bruzzi 1,2*, M. Brianzi 2, M. Bucciolini 2,3, G. A. P. Cirrone 4, C. Civinini 2, G. Cuttone 4, D. Lo Presti 5,6, S. Pallotta 2,3, C. Pugliatti 5,6, N. Randazzo 5, F. Romano 4,7, V. Sipala 8,9, M. Scaringella 1, C. Stancampiano 5,6, C. Talamonti 2,3, M. Tesi 1, E. Vanzi 10, M. Zani 2,3 1 Physics Department, University of Florence, Italy 2 INFN - Florence Division, Italy 3 Clinical Physiopathology Department, University of Florence, Florence, Italy 4 INFN - Laboratori Nazionali del Sud, Catania, Italy, 5 INFN - Catania Division, Italy 6 Physics Department, University of Catania, Catania, Italy 7 Centro Studi e Ricerche e Museo Storico della Fisica, Rome, Italy 8 Chemistry and Pharmacy Department, University of Sassari, Sassari, Italy 9 INFN Cagliari Division, Italy 10 SOD Fisica Medica, Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy * Spokesperson

2. The pCT Principle Direct measurement of proton stopping power Single particle proton tracking: silicon strip detectors → MLP Residual energy measurement: crystal calorimeter → energy loss 2 PARAMETERVALUE Proton beam energy 250 -270 MeV Proton beam rate1 MHz Spatial resolution< 1 mm Electronic density resolution <1% Detector radiation hardness >1000 Gy Dose per scan< 5 cGy 2 P1P1 P2P2 P3P3 P4P4 z x y Single event information can be processed by reconstruction algorithms to produce tomographic images. Mara Bruzzi Consuntivo PRIMA+ -CSN5 2 Maggio 2013 Roma

3. First prototype for pCT 53x53 mm 2 active area Data rate up to 10-20 kHz 3 Designed, m anufactured and tested with 62 & 180 MeV proton beams P1 P2 P3 P4 x y Mara Bruzzi Consuntivo PRIMA+ -CSN5 2 Maggio 2013 Roma

4. Parallel strip read-out Local data storaging during measurement. Ethernet data download at measurement completion. Tracker module 4 Mara Bruzzi Consuntivo PRIMA+ -CSN5 2 Maggio 2013 Roma

5. 6.6 x 1.6 mm 2 32 inputs - 32 outputs 670 mW power consumption Vcc=+3.3 V DETECTORS AND Front-end asic 5 High resistivity n-type Float Zone Silicon 200  m thick - Single side microstrip Squared size 5.25 x 5.25 cm 2 256 strips, AC coupled – width: 60  m, pitch 200  m Mara Bruzzi Consuntivo PRIMA+ -CSN5 2 Maggio 2013 Roma

6. 6 4 YAG:Ce scintillating crystals 30 x 30 mm 2 x 100mm each 4 Photodiodes 18mmx18 mm Calorimeter DAQ ARCHITECTURE 6 4 commercial front-end (Charge Sensitive Amplifier & shaper ) Mara Bruzzi Consuntivo PRIMA+ -CSN5 2 Maggio 2013 Roma

7. Profile along diagonal holes One cluster in each plane Cut on the difference between the “entrance“ and “exit” angle Test beam at LNS - 62 Mev protons radiography 7 P1 P2 P3 P4 Beam pipe Mara Bruzzi Consuntivo PRIMA+ -CSN5 2 Maggio 2013 Roma Sigma=0.170 ± 0.09 mm FWHM = 0.400± 0.212 mm Residual energy (MeV)

8. Test beam at Svedberg Laboratory - Uppsala pCT prototype mounted on 180 MeV protons beam line Radiography without filtering 8 Hole thickn. (cm) 1 1,5 2,3 3,3 4,5 6 8 10 Pmma cylindrical phantom with holes 14 cm total thickness Not to scale Mara Bruzzi Consuntivo PRIMA+ -CSN5 2 Maggio 2013 Roma

9. FIRST TOMOGRAPHIES: Test with 62 MeV protons PMMA phantom: diameter 2 cm, height 4 cm – holes  &6 mm, length 2 cm 36 projections (10 degrees steps) 2 cm Mara Bruzzi Consuntivo PRIMA+ -CSN5 2 Maggio 2013 Roma

10. Data analysis: the tomographic equation Definition of the tomographic equation (Wang, Med.Phys. 37(8), 2010: 4138) « projection » Unknown stopping power distribution (at E 0 ) Evaluation of the “projection” term (through numerical integration starting from NIST tables and using the measured E res ) E res Wang projection Mean measured residual energy plotted at P3 plane Corresponding Wang projections Mara Bruzzi Consuntivo PRIMA+ -CSN5 2 Maggio 2013 Roma

11. FIRST TOMOGRAPHIES: Test with 62 MeV protons We defined a plane parallel to detector’s planes passing through the phantom axis. Plane is sampled in a 256 x 256 matrix, 200µm pixel size. For each event, associated projection bin is determined by the intersection of the line connecting P2 and P3 impact points with the plane. P2P3 Mara Bruzzi Consuntivo PRIMA+ -CSN5 2 Maggio 2013 Roma

12. TOMOGRAPHIC RECONSTRUCTION RESULTS Butterworth filter: order 2, cut-off 20/128 of the Nyquist freq. Good quality images without cuts: possibility of reducing acquisition times and dose in patient procedures Mara Bruzzi Consuntivo PRIMA+ -CSN5 2 Maggio 2013 Roma

13. upgrade: pre-clinical prototype Increase 4x of the active area On-line data acquisition Data rate up to 1 MHz 13 A new prototype based on the same technology, to meet pre-clinical demands now under development tracker calorimeter 4x1 silicon detectors 5x20 cm 2 active area 7x2 YAG crystals 6x21 cm 2 active area Rectangular shape to perform tomography in slices X1 FE X2 FE X3 FE X4 FE top M. Scaringella et al. RESMDD12 Conference Florence October, 2012 Mara Bruzzi Consuntivo PRIMA+ -CSN5 2 Maggio 2013 Roma

14. 14 7x2 YAG:Ce scintillating crystals 30 x 30 mm 2 x 100mm each. Photodiodes assembled. Now under test (RDH) Mara Bruzzi Consuntivo PRIMA+ -CSN5 2 Maggio 2013 Roma

15. Infos sul progetto 15 Titolo del progetto PRIMA+ Responsabile nazionale Mara Bruzzi Data inizio 01-01-2010 - data fine 31-12-2012 area (acceleratori,interdisciplinare,rivelatori,elettronica/computing) in CSN5 Sezioni coinvolte INFN Firenze, INFN Catania, LNS Responsabil locali: M. Bruzzi, N. Randazzo, G.A.P. Cirrone 2) Numero di partecipanti (media) 21 FTE (media) 5 Fondi INFN ricevuti 1)missioni interne 78.5 kEuro 2)inventariabile/costruzione apparati 100.5 kEuro 3)consumo 99.5 kEur Fondi esterni (Università) Assegni di ricerca Mara Bruzzi Riunione RDH 22 Aprile 2013 Roma

16. Pubblicazioni PRIMA+ ISI [1] Bulletti, A., Capineri, L., Dunn, B.D., Bruzzi, M., Investigation of resistivity variation of printed circuit board laminates due to aging, IEEE Transactions on Components, Packaging and Manufacturing Technology Volume 2, Issue 12, 2012, Article number6352945, Pages 2001-2006. [2] Mori, R., Bruzzi, M., Cartiglia, M., Christophersen, M., Ely, S., Martinez-Mckinney, F., Phlips, B., Sadrozinski, H.W.F., Fadeyev, V., Charge collection measurements on slim-edge microstrip detectors Journal of Instrumentation, Volume 7, Issue 5, May 2012, Article number P05002. [3] Sipala, V; Brianzi, M; Bruzzi, M; Bucciolini, M; Cirrone, GAP; Civinini, C; Cuttone, G; Lo Presti, D; Pallotta, S; Randazzo, N; Romano, F; Stancampiano, C; Scaringella, M; Talamonti, C; Tesi, M PRIMA: An apparatus for medical application Nucl. Inst. and Meth. A 658-1 (2011) 73-77 [4] Cirrone, GAP; Bucciolini, M; Bruzzi, M; Candiano, G; Civinini, C; Cuttone, G; Guarino, P; Lo Presti, D; Mazzaglia, SE; Pallotta, S; Randazzo, N; Sipala, V; Stancampiano, C; Talamonti, C Monte Carlo evaluation of the Filtered Back Projection method for image reconstruction in proton computed tomography, Nucl. Inst. and Meth. A658-1 (2011) 78-83 [5] D. Menichelli et al., "Characterization of a silicon strip detector and a YaG:Ce calorimeter for a proton computed radiography apparatus," IEEE Trans. Nucl.Sci. 2010 [6] Civinini, C et al. Towards a proton imaging system Nucl. Inst. and Meth. A623-1 (2010) 588-590 [7] C. Talamonti et al., "Proton Radiography for clinical applications," Nucl.Instr.Meth. A 612; (2010) 571. [8] V. Sipala et al., "A proton imaging device: design and realization status," Nucl. Instr. Meth. A 612 (2010) 566–570. 16 Mara Bruzzi Riunione RDH 22 Aprile 2013 Roma

17. Pubblicazioni PRIMA+ Non ISI [1] Sipala, V; Brianzi, M; Bruzzi, M; Bucciolini, M; Cirrone, GAP; Civinini, C; Cuttone, G; Lo Presti, D; Randazzo, N; Scaringella, M; Stancampiano, C; Talamonti, C; Tesi, M Proton imaging apparatus for protontherapy application IL NUOVO CIMENTO C, vol. 34, (2011) p. 11-17 [2] Sipala V, Randazzo N, Bruzzi M, Bucciolini M, Pallotta S, Scaringella M, Talamonti C, Tesi M, Civinini C, Brianzi M, Cirrone GAP, Cuttone G, Romano F, Upgrade of the proton Computed Tomography system of the PRIMA project Proceedings of Science, PoS(RD11)013 (2012) [3] Sipala, V., Bruzzi, M., Brianzi, M., Bucciolini, M., Cirrone, G.A.P., Civinini, C., Cuttone, G., Lo Presti, D., Pallotta, S., Randazzo, N., Romano, F., Scaringella, M., Stancampiano, C., Talamonti, C., Tesi, M. Tomographic images by proton Computed Tomography system for proton therapy applications IEEE Nuclear Science Symposium Conference Record 2012, Article number6152644, Pages 3505-3507. 17 Mara Bruzzi Riunione RDH 22 Aprile 2013 Roma

18. Presentazioni a congresso 18 Mara Bruzzi Riunione RDH 22 Aprile 2013 Roma [1] Civinini, C PRIMA+: A proton Computed Tomography apparatus Incontri di Fisica delle Alte Energie (IFAE 2012), Ferrara, Italy, Apr. 11-13, 2012. [2] Sipala V. A proton Computed Tomography System for medical Application IWORID – International Workshop on Radiation Imaging Detectors 1-5 JULY 2012 Figueira da Foz, Coimbra, PORTUGAL [3] Vanzi E. The PRIMA collaboration: preliminary results in FBP reconstruction of pCT data, Radiation Effects on Semiconductor Materials Detectors Devices (RESMDD) 10 – 13 ottobre 2012 Firenze Italy. [4] Scaringella M., The PRIMA (Proton Imaging) collaboration: development of a proton Computed Tomography apparatus, Radiation Effects on Semiconductor Materials Detectors Devices (RESMDD) 10 – 13 ottobre 2012 Firenze Italy. [5] Bruzzi M. The PRIMA Collaboration: Status of the Development of a Proton Computed Tomography Scanner, 2012 Nuclear Science Symposium and Medical Imaging Conference, October 29 - November 3, 2012, Anaheim, California [6] Talamonti C. PRIMA Proton Imaging for Clinical Application 2012 Nuclear Science Symposium and Medical Imaging Conference October 29 - November 3, 2012, Anaheim, California [7] Talamonti C. Development of a Proton Computed Tomography System for Pre-Clinical Tests 2012 Nuclear Science Symposium and Medical Imaging Conference October 29 - November 3, 2012, Anaheim, California [8] Bruzzi M. Development and characterization under intensity modulated radiotherapy beam of a large area bidimensional dosimeter made with p-type epitaxial silicon 2012 Nuclear Science Symposium and Medical Imaging Conference October 29 - November 3, 2012, Anaheim, California [9] Sipala, V., Tomographic images by proton Computed Tomography system for proton therapy applications IEEE Nuclear Science Symposium and Medical Imaging Conference, NSS/MIC 2011; Valencia; Spain; 23-29 October 2011 [10] Sipala V, Upgrade of the proton Computed Tomography system of the PRIMA project RD11 Firenze July 2011. [11] Sipala, V PRIMA: An apparatus for medical application 8th International Conference on Radiation Effects on Semiconductor Materials, Detectors and Devices (RESMDD) Florence, October 12–15, 2010 [12] Cirrone, GAP Monte Carlo evaluation of the Filtered Back Projection method for image reconstruction in proton computed tomography 8th International Conference on Radiation Effects on Semiconductor Materials, Detectors and Devices (RESMDD) Florence, October 12–15, 2010. [13] Sipala, V Proton imaging apparatus for protontherapy application Incontri di Fisica Applicata (IFA 2010), La Biodola, Isola d'Elba, Italy, 24-28 May 2010

19. Conclusions A pCT apparatus has been designed and built based on: – Silicon microstrip detectors 5x5 cm 2 active area – YAG:Ce cristal calorimeter The prototype has been tested under proton beams with energies up to 180 MeV with promising results. First tomographic images were reconstructed with FBP with encouraging results. Even using the information on two planes only and without cuts on events good quality images were obtained. A new prototype with larger area (5x20 cm 2 ) is under development for pre- clinical validation. Future progress in WP3 RDH. 19 Mara Bruzzi Consuntivo PRIMA+ -CSN5 2 Maggio 2013 Roma

20. PHANTOM The phantom is custom-made. It is cylindrical and made of PolyMetilMetacrilate (PMMA) and it has holes of different size and depth. The phantom diameter (40 mm) has been chosen according to the tracker field of view while the phantom length (140 mm), according to beam quality. depth Not to scale

21. Resolution evaluation The edge of the phantom is fitted with an erf function on 20 slices in the homogeneous region. The mean FWHM of the LSF over the 20 slices was evaluated and used to quantify resolution. The derivative of the erf function is a Gaussian function that describes the Line Spread Function (LSF) of the imaging system. FWHM=0.9±0.1mm Noise=2.4% Mara Bruzzi Riunione RDH 22 Aprile 2013 Roma

22. WP3: upgrade status 22 I rivelatori a silicio sono stati consegnati nella seconda metà del 2012 Il nuovo calorimetro 7x2 è stato assemblato, ora sotto test Nuovi chip prodotti e consegnati ora sotto test Nuova scheda tracker Si disponibile dai primi di maggio Integrazione di un modulo xy in silicio del nuovo tracker con calorimetro e test sotto fascio programmato per la seconda metà del 2013 Mara Bruzzi Consuntivo PRIMA+ -CSN5 2 Maggio 2013 Roma

23. Upgraded si module 23 Mara Bruzzi Riunione RDH 22 Aprile 2013 Roma Front-end chips Slave FPGA Master FPGA Serial communication to central DAQ Mixed analog/digital, 12 layers Detector area

24. Data analysis: the tomographic equation Definition of the tomographic equation (Wang, Med.Phys. 37(8), 2010: 4138) « projection » Unknown stopping power distribution (at E 0 ) Evaluation of the “projection” term (through numerical integration starting from NIST tables and using the measured E res ) E res Wang projection Mean measured residual energy plotted at P3 plane Corresponding Wang projections Mara Bruzzi Consuntivo PRIMA+ -CSN5 2 Maggio 2013 Roma