Journes jeunes chercheurs SFPM Gd R MI 2

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Journées jeunes chercheurs SFPM / Gd. R MI 2 B – 20/11/2019 ION BEAM

Journées jeunes chercheurs SFPM / Gd. R MI 2 B – 20/11/2019 ION BEAM MONITORING USING BRMESSTRAHLUNG X-RAYS F. Ralite 1 ; C. Koumeir 2 ; A. Guertin 1 ; F. Haddad 1, 2 ; N. Servagent 1 ; V. Métivier 1 1 Laboratoire de physique subatomique et des technologies associées : SUBATECH, Nantes, France 2 GIP ARRONAX, Saint-Herblain, France Contact : flavien. [email protected] in 2 p 3. fr

RALITE – Présentation SFPM – 14/06/2018 CONCLUSION CONTEXTFlavien – BEAM MONITORING METHOD – RESULTS–

RALITE – Présentation SFPM – 14/06/2018 CONCLUSION CONTEXTFlavien – BEAM MONITORING METHOD – RESULTS– RADIOTHERAPY External radiotherapy Brachytherapy Internal Vectorized Radiotherapy Ionizing radiations from particle accelerator Radioactive source in contact with the tumor • Photon beam Radionucleide coupled with chemical vector • Electron beam • Ion beam Framework of our study PROTON BEAM : High and localised deposited dose (Bragg peak ) PROTONS PHOTONS (Particle Therapy, Spinger, 2016) (V. Verma, CCO, 2016) Figure 1 : Schematic view of the depth-dose profile for photon and proton beams. Flavien RALITE Figure 2 : Comparison of the dose distribution obtained with proton beams (left) and photon beams (right) for the treatment of occular cancer Journées jeunes chercheurs SFPM / Gd. R MI 2 B - Nantes - 12/11/2019 2

RALITE – Présentation SFPM – 14/06/2018 CONCLUSION CONTEXTFlavien – BEAM MONITORING METHOD – RESULTS–

RALITE – Présentation SFPM – 14/06/2018 CONCLUSION CONTEXTFlavien – BEAM MONITORING METHOD – RESULTS– SPREAD OUT BRAGG PEAK Normal tissue Bragg peak: Single energy beam Tumor SOBP : Multi energy beam Normal tissue Patient Skin Proton Beam 68 Me. V Figure 3 : Spread-out Bragg Peak from proton beam of 68 Me. V. High and localised deposited dose: • Ion beam moniroting required • Non-invasive and online methods Flavien RALITE Journées jeunes chercheurs SFPM / Gd. R MI 2 B - Nantes - 12/11/2019 3

RALITE – Présentation SFPM – 14/06/2018 CONCLUSION CONTEXTFlavien – BEAM MONITORING METHOD – RESULTS–

RALITE – Présentation SFPM – 14/06/2018 CONCLUSION CONTEXTFlavien – BEAM MONITORING METHOD – RESULTS– SECONDARY PARTICLE PRODUCTION Interaction Proton/Matter: • X-ray production • Ionisation / Excitation • Bremsstrahlung Beam H+ • γ photon production • Gamma prompt production from nuclear interaction • Annihilation of positron from β+ emitter created by the radiation • Secondary electron Figure 4 : Schematic view of particles emitted from the irradiated medium after interaction with a proton beam. Flavien RALITE Journées jeunes chercheurs SFPM / Gd. R MI 2 B - Nantes - 12/11/2019 4

RALITE – Présentation SFPM – 14/06/2018 CONCLUSION CONTEXTFlavien – BEAM MONITORING METHOD – RESULTS–

RALITE – Présentation SFPM – 14/06/2018 CONCLUSION CONTEXTFlavien – BEAM MONITORING METHOD – RESULTS– NON-INVASIVE ONLINE BEAM MONITORING g detector XR detector g PET g XR Different approaches: • Positron Emission Tomography • Online beam range verification • Beam range uncertainties (several mm) Ammar, Phys. Med. Biol. , 2014 Robert, Phys. Med. Biol. , 2013 Beam H+ e+ XR g g • γ prompt measurment • Online beam range monitoring • Beam range uncertainties (several mm) Verburg, Phys. Med. Biol. , 2014 Testa, Rad. Env. Biophy. , 2010 • X-ray bremsstrahlung • Beam imaging • Beam range monitoring • Beam range uncertainties (? ) Figure 5 : Schematic view of the different online beam monitoring approach. Flavien RALITE Journées jeunes chercheurs SFPM / Gd. R MI 2 B - Nantes - 12/11/2019 Yamaguchi, Phys. Med. Biol. , 2012 Yamaguchi, Nucl. Inst. Meth. A. , 2016 5

RALITE – Présentation SFPM – 14/06/2018 CONCLUSION CONTEXTFlavien – BEAM MONITORING METHOD – RESULTS–

RALITE – Présentation SFPM – 14/06/2018 CONCLUSION CONTEXTFlavien – BEAM MONITORING METHOD – RESULTS– BREMSSTRAHLUNG X-RAYS XR NB Bremsstrahlung: • X-ray emissions from the deceleration of the charges particles in the medium e. XR Beam H+ 68 Me. V SEB e- XR AB • X-ray energy is proportional to the energy loss of the charged particles • Continuous component of the X-ray spectrum Composantes du Bremsstrahlung : • • QFEB : Quasi-Free Electron Bremsstrahlung SEB : Secondary Electron Bremsstrahlung AB : Atomic Bremsstrahlung NB : Nuclear Bremsstrahlung • Cross section: XR QFEB Figure 6 : Schematic view fo the bremsstrahlung X-rays emitted from different processes. Ishi, Rad. Phys. Chem. , 2006 Miraglia, Phys. Rev. , 1989 Pasher, Phys. Rev. , 1990 Bremsstrahlung interest: • Directly link to the deposited dose • Significant cross sections Ishi, Rad. Phys. Chem. , 2006 • Sensitive to the medium attenuation • Low energy : elementary composition of the medium • High energy : density of the medium Flavien RALITE Journées jeunes chercheurs SFPM / Gd. R MI 2 B - Nantes - 12/11/2019 6

RALITE – Présentation SFPM – 14/06/2018 CONCLUSION CONTEXTFlavien – BEAM MONITORING METHOD – RESULTS–

RALITE – Présentation SFPM – 14/06/2018 CONCLUSION CONTEXTFlavien – BEAM MONITORING METHOD – RESULTS– DEPOSITED DOSE Method developed for radiobiology: Schwob, Rad. Pro. Dosi. , 2015 From measure to the deposited dose • Demonstrated for alpha particles • Valid for homogeneous medium with a thin thickness Linear Energy Transfert Beam fluence Determined by Monte-Carlo simulations (SRIM/TRIM) Conversion factor (Me. V/g in J/kg) Aim of the study • Proof of feasability to monitor proton beam using bremsstrahlung X-rays Detection efficiency Flavien RALITE In this state, not applicable in clinic: • Heterogeneous meidum • Impossibility to get the LET • Medium attenuation • Cross section measurement • Fundamental study to model the bremsstrahlung spectrum Total cross section of bremsstrahlung X-rays Medium attenuation • Extend the method to clinical application Journées jeunes chercheurs SFPM / Gd. R MI 2 B - Nantes - 12/11/2019 7

RALITE – Présentation SFPM – 14/06/2018 CONCLUSION CONTEXTFlavien – BEAM MONITORING METHOD – RESULTS–

RALITE – Présentation SFPM – 14/06/2018 CONCLUSION CONTEXTFlavien – BEAM MONITORING METHOD – RESULTS– H+ Beam: 17 Me. V 30 Me. V 40 Me. V 50 Me. V EXPERIMENTAL SET-UP Silicon detector: • Promotes the detection of low energy photons (between 1 and 30 ke. V) • Minimise the target-detector distance • Crystal thickness: 450µm Figure 7 : Schematic view of the experimental set-up to measure bremsstrahlung spectra and cross sections Two acquisitions: • Background: measure of the ambiant activation and fluence with the beam stop • Measure of the bremsstrahlung X-rays emitted by the PMMA target Flavien RALITE Journées jeunes chercheurs SFPM / Gd. R MI 2 B - Nantes - 12/11/2019 8

RALITE – Présentation SFPM – 14/06/2018 CONCLUSION CONTEXTFlavien – BEAM MONITORING METHOD – RESULTS–

RALITE – Présentation SFPM – 14/06/2018 CONCLUSION CONTEXTFlavien – BEAM MONITORING METHOD – RESULTS– EXPERIMENTAL SET-UP Figure 9 : Photography of the beam line output with a silicon detector looking at the PMMA target. Characteristic peak of Argon Bremsstrahlung Figure 8 : Photography of the experimental set-up. Flavien RALITE Figure 10 : Raw spectra of background and bremsstrahlung acquisitions Journées jeunes chercheurs SFPM / Gd. R MI 2 B - Nantes - 12/11/2019 9

RALITE – Présentation SFPM – 14/06/2018 CONCLUSION CONTEXTFlavien – BEAM MONITORING METHOD – RESULTS–

RALITE – Présentation SFPM – 14/06/2018 CONCLUSION CONTEXTFlavien – BEAM MONITORING METHOD – RESULTS– CROSS SECTION RESULTS • Significant agreement between the experiemental data and the model • The disagreement at high energy photon could be explained with the noise induced by the target • Fundamental contributions of the spectrum • QFEB • SEB Figure 11: Bremsstrahlung cross sections for a carbon target bombarded with proton beams of 17 Me. V, 30 Me. V, 40 Me. V and 50 Me. V. Flavien RALITE Journées jeunes chercheurs SFPM / Gd. R MI 2 B - Nantes - 12/11/2019 10

RALITE – Présentation SFPM – 14/06/2018 CONCLUSION CONTEXTFlavien – BEAM MONITORING METHOD – RESULTS–

RALITE – Présentation SFPM – 14/06/2018 CONCLUSION CONTEXTFlavien – BEAM MONITORING METHOD – RESULTS– CROSS SECTION RESULTS • Cross section measured are closed to litterature • Ishii : For proton beam of 20 Me. V at the photon energy of 7 kev : 0. 01 barn/ke. V. sr • Measure : For proton beam of 17 Me. V at the photon energy of 7 ke. V : 0. 008 barn/ke. V. sr (Ishii, NIM B. , 2018) • The disagreement at high energy photon could be explained with the noise induced by the target Figure 12: Comparison of the bremsstrahlung cross sections for a Carbon target bombarded with proton beams of 17 Me. V/u, and 20 Me. V (from Ishii work). Flavien RALITE Journées jeunes chercheurs SFPM / Gd. R MI 2 B - Nantes - 12/11/2019 11

RALITE – Présentation SFPM – 14/06/2018 CONCLUSION CONTEXTFlavien – BEAM MONITORING METHOD – RESULTS–

RALITE – Présentation SFPM – 14/06/2018 CONCLUSION CONTEXTFlavien – BEAM MONITORING METHOD – RESULTS– BREMSSTRAHLUNG MODEL RESULTS • PMMA target : significant agreement between model and bremsstrahlung spectra • Signal measured comes from bremsstrahlung • Shape of the spectra: • Photon with an Energy > 15 ke. V are attenuated because of the detector efficiency • Photon with an energy < 5 ke. V are attenuated because of the air attenuation Figure 13: Exprimental (grey line) and simulated (black dashed line) bremsstrahlung spectra from the 1000µm PMMA thick target bombarded with proton beams of 16. 9 Me. V, 30. 1 Me. V, 39. 3 Me. V and 49. 6 Me. V. Flavien RALITE Journées jeunes chercheurs SFPM / Gd. R MI 2 B - Nantes - 12/11/2019 12

RALITE – Présentation SFPM – 14/06/2018 CONCLUSION CONTEXTFlavien – BEAM MONITORING METHOD – RESULTS–

RALITE – Présentation SFPM – 14/06/2018 CONCLUSION CONTEXTFlavien – BEAM MONITORING METHOD – RESULTS– BREMSSTRAHLUNG MODEL RESULTS Photon with an Energy > 15 ke. V are attenuated because of the detector efficiency Figure 14: Silicon drift detector efficiency Photon with an energy < 5 ke. V are attenuated because of the target-detector distance and the detection efficiency Figure 13: Exprimental (grey line) and simulated (black dashed line) bremsstrahlung spectra from the 1000µm PMMA thick target bombarded with proton beams of 16. 9 Me. V, 30. 1 Me. V, 39. 3 Me. V and 49. 6 Me. V. Flavien RALITE Journées jeunes chercheurs SFPM / Gd. R MI 2 B - Nantes - 12/11/2019 13

RALITE – Présentation SFPM – 14/06/2018 CONCLUSION CONTEXTFlavien – BEAM MONITORING METHOD – RESULTS–

RALITE – Présentation SFPM – 14/06/2018 CONCLUSION CONTEXTFlavien – BEAM MONITORING METHOD – RESULTS– BEAM ENERGY MONITORING Emean increases with the beam energy Beam Energy (Me. V) 16. 9 30. 1 39. 3 49. 6 Emean (ke. V) FWHM increases with the beam energy • The bremsstrahlung spectrum hardening with the increase of the beam energy is explained with the bremsstrahlung cross sections variations • Proton beam energy can be monitored with the bremsstrahlung X-rays • Observation are only valid for this set-up because of the detector efficiency and medium attenuation Fraction of high energy photon (>15 ke. V) increases Figure 15: Bremsstrhalung spectra from 1000µm PMMA thick target bombarded with 16. 9 Me. V, 30. 12 Me. V, 39. 3 Me. V and 49. 6 Me. V proton beams (energy at the target surface). Flavien RALITE Journées jeunes chercheurs SFPM / Gd. R MI 2 B - Nantes - 12/11/2019 14

RALITE – Présentation SFPM – 14/06/2018 CONCLUSION CONTEXTFlavien – BEAM MONITORING METHOD – RESULTS–

RALITE – Présentation SFPM – 14/06/2018 CONCLUSION CONTEXTFlavien – BEAM MONITORING METHOD – RESULTS– BEAM RANGE MONITORING WITH BREMSSTRAHLUNG X-RAYS Flavien RALITE Journées jeunes chercheurs SFPM / Gd. R MI 2 B - Nantes - 12/11/2019 15

RALITE – Présentation SFPM – 14/06/2018 CONCLUSION CONTEXTFlavien – BEAM MONITORING METHOD – RESULTS–

RALITE – Présentation SFPM – 14/06/2018 CONCLUSION CONTEXTFlavien – BEAM MONITORING METHOD – RESULTS– BREMSSTRAHLUNG SCAN Silicon X-ray drift detector Proton beam output Ionisation Chamber Kapton ouput window 50µm Measure of the beam fluence (water thickness equivalence 120µm) Measure of the bremsstrahlung emitted from water Beam Collimator Aluminium ø=5 mm X-ray Collimator Pb ø=0. 5 cm 13, 2 cm 20 cm 11, 5 cm Proton Beam 68 Me. V Y Titanium entrance window 100µm Sliding motion of the water tank 8, 5 cm Z X Water tank Biological medium surrogate Figure 16: Experimental set-up of the bremsstrahlung scan for a water tank bombarded with proton beam of 68 Me. V. Flavien RALITE Journées jeunes chercheurs SFPM / Gd. R MI 2 B - Nantes - 12/11/2019 16

RALITE – Présentation SFPM – 14/06/2018 CONTEXTFlavien – BEAM MONITORING METHOD – RESULTS –

RALITE – Présentation SFPM – 14/06/2018 CONTEXTFlavien – BEAM MONITORING METHOD – RESULTS – CONCLUSION BREMSSTRAHLUNG SCAN • Bremsstrahlung spectra evolve with the beam energy • Link with the deposited dose should be investigated Figure 17: Depth-dose profile of the FLUKA simulation (Data were normalised). Bremstrahlung spectra at different depth are also presented. Flavien RALITE Journées jeunes chercheurs SFPM / Gd. R MI 2 B - Nantes - 12/11/2019 17

RALITE – PLATFORM Présentation SFPMMONITORING – 14/06/2018 CONTEXTFlavien – RADIOBIOLOGY – BEAM – CONCLUSION

RALITE – PLATFORM Présentation SFPMMONITORING – 14/06/2018 CONTEXTFlavien – RADIOBIOLOGY – BEAM – CONCLUSION AND OUTSKIRTS • Ion beam monitoring using Bremsstrahlung X-rays • Cross section measured on carbon target • Bremsstrahlung model validated with the experimental data • significant sensivity for the method • Beam energy can be monitored with the bremsstrahlung for proton beams in the frame of radiobiology experiment • Results are only valid for the set-up used because of the detector efficiency and the medium attenuation • Outskirts • Monte-Carlo simulations are required to improve the set-up and to develop an X-ray camera • Link with the deposited dose should be investigate Flavien RALITE Journées jeunes chercheurs SFPM / Gd. R MI 2 B - Nantes - 12/11/2019 18

Flavien RALITE – Présentation SFPM – 14/06/2018 REFERENCES • Robet C. et al, Distributions

Flavien RALITE – Présentation SFPM – 14/06/2018 REFERENCES • Robet C. et al, Distributions of secondary particles in protons and carbon-ion therapy, Phy. Med. Biol. 58, (2013) • J. M. Verburg et al, Proton range verification though prompt gamma-ray spectroscopy, Phy. Med. Biol. , 59, 7089 -7106, (2014). • Testa E. et al, Real-time monitoring of the Bragg peak position by means of single poton detection, Radia. Env. Biophy. , 49, 337 -43, (2010) • M. Yamaguchi et al, Secondary-Electron-Bremsstrahlung imaging for proton therapy, Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, detectors and Associated Equipment, 833, 199 -207, (2016). • L. Schwob et al, New beam monitoring tool for radiobiology experiments at the cyclotron Arronax, Radiation Protection Dosimetry, 166(1 -4), 257 -60, (2015). • K. Ishii et al, Continuous X-rays produced in light-ion-atom collisions, Radiation Physics and Chemistry, 75, 1135 -1163, (2006). • K. Ishii et al, High energy limit of atomic bremsstrahlung, Nuclear Instruments and Methods in Physics Research Section A: Beam Interactions with Materials and Atoms, 99, 163 -165, (2006). • J. E. Miraglia, Scaling laws for secondary-electron-bremsstrahlung, Physical Review A, 39, 2908 -2913, (1989). • M. Pacher et al, Scaling laws and polarization of atomic bremsstrahlung, Physical Review A, 41, 2574 -2579, (1990) • K. Ishii et al, Theoretical detection limit of PIXE analysis using 20 Me. V proton beams, Nucl. Instr. and Meth. In Phys. Res. B, 417, 37 -40, (2018). • M. J. Berger et al, Stopping power and range tables for electrons, protons and helium ions, NIST standard reference database 124, (2017). • Ziegler J. F. et al. , 2010. SRIM – The Stopping and range of ions in matter (2010), Nuclear Instrument and Methods in Physics Research, Section B, June 2010 181: 1823 • F. Haddad et al. Arronax, a High Energy and High Intensity Cyclotron for Nuclear Medicine, Eur. J. Nucl. Med. Mol. Imaging, 35, 1377 -1387, (2008). Flavien RALITE Journées jeunes chercheurs SFPM / Gd. R MI 2 B - Nantes - 12/11/2019 19

Flavien RALITE – Présentation SFPM – 14/06/2018 APPENDIX INCIDENT PARTICLE MONITORING Bremsstrahlung yield grows

Flavien RALITE – Présentation SFPM – 14/06/2018 APPENDIX INCIDENT PARTICLE MONITORING Bremsstrahlung yield grows with the proton beam energy Bremsstrahlung yield saturation Good agreement with the model The number of incident particle can be monitoring, in the following conditions : • • • Saturation of the measured bremsstrahlung yield Medium thickness larger than the minimum thcikness required to have saturation conditions Homogeneous medium Knowing the TEL of the proton beam, the deposited dose can be monitored with the monitoring of the number of incident particles Figure 15 : Bremsstrahlung yield versus the PMMA thickness target bombarded with proton beam of 16. 9 Me. V/U, 30. 12 Me. V, 39. 3 Me. V and 49. 6 Me. V. Flavien RALITE Journées jeunes chercheurs SFPM / Gd. R MI 2 B - Nantes - 12/11/2019 20

Flavien RALITE – Présentation SFPM – 14/06/2018 APPENDIX INCIDENT PARTICLE MONITORING Good agreement with

Flavien RALITE – Présentation SFPM – 14/06/2018 APPENDIX INCIDENT PARTICLE MONITORING Good agreement with the model Figure 15 : Bremsstrahlung yield versus the PMMA thickness target bombarded with proton beam of 16. 9 Me. V/U, 30. 12 Me. V, 39. 3 Me. V and 49. 6 Me. V. Flavien RALITE Journées jeunes chercheurs SFPM / Gd. R MI 2 B - Nantes - 12/11/2019 21

Flavien RALITE – Présentation SFPM – 14/06/2018 APPENDIX BREMSSTRAHLUNG SCAN Silicon X-ray drift detector

Flavien RALITE – Présentation SFPM – 14/06/2018 APPENDIX BREMSSTRAHLUNG SCAN Silicon X-ray drift detector Proton beam output Beam Collimator Measure of the bremsstrahlung emitted from water Ionisation Chamber Measure of the beam fluence Water tank Biological medium surrogate Figure 17: Photographies of the experimental set-up of the bremsstrahlung scan for a water tank bombarded with proton beam of 68 Me. V. Flavien RALITE Journées jeunes chercheurs SFPM / Gd. R MI 2 B - Nantes - 12/11/2019 22