Applications in Medicine

1. Applications in Medicine Maria Grazia Pia INFN Sezione di Genova Symposium on Geant4 Applications 9th ICATPP Conference Como, 17-21 October 2005

2. Thanks to Simone Giani for organizing this symposium! GEANT4 SYMPOSIUM PROGRAMME 20 Oct 2005 INDUSTRY The Radiation Imager Virtual Laboratory GENERAL ELECTRICS – by R.Thompson MonteCarlo Simulation of PET Systems SIEMENS - CPS – by M.Conti SPACE Applications of G4 for the ESA Space Programme EUROPEAN SPACE AGENCY – by G.Santin GEANT4 Applications for NASA Space Missions SLAC - NASA GSFC - Vanderbilt U. – by M.Asai MEDICINE G4 in Development of New Radiotherapy Treatments KAROLINSKA (Sweden) – by A.Brahme GEANT4 Applications in Medicine INFN (Italy) – by M.G.Pia TECHNOLOGY GEANT4 Application to Ion-Therapy in Japan KEK (Japan) – by K.Amako Open-GATE Project INSERM (France) – by I.Buvat PHYSICS Detector Simulation in HEP CERN (CH) – by J.P.Wellisch GEANT4 Accelerator Applications IMPERIAL COLLEGE (UK) – by M.Ellis

3. Courtesy of L. Beaulieu et al., Laval Radiation Protection Courtesy of J. Perl, SLAC Medicalapplications PET, SPECT Courtesy of GATE Collaboration Courtesy of B. Mascialino et al., INFN Genova Radiotherapy with external beams, IMRT Courtesy of P. Cirrone et al., INFN LNS Hadrontherapy Brachytherapy Courtesy of S. Guatelli et al,. INFN Genova

4. Mars and Leukemia Symposium on Geant4 Applications 9th ICATPP Conference Como, 17-21 October 2005 Maria Grazia Pia INFN Sezione di Genova

5. Astrophysics • Planetary exploration has grown into a major player in the vision of space science organizations like ESA and NASA • The study of the effects of space radiation on astronauts is an important concern of missions for the human exploration of the solar system • The radiation hazard can be limited: • selecting traveling periods and trajectories • providing adequate shielding in the transport vehicles and surface habitats Radiation Protection

6. Vehicle concepts SIH - Simplified Inflatable Habitat Conventional approach Rigid Habitat A layer of Al (structure element of the ISS) Innovative concepts under study Inflatable habitat A multilayer structure consisting of: • MLI: external thermal protection blanket - Betacloth and Mylar • Meteoroid and debris protection - Nextel (bullet proof material) and open cell foam • Structural layer - Kevlar • Rebundant bladder - Polyethylene, polyacrylate, EVOH, kevlar, nomex Materials and thicknesses by ALENIA SPAZIO

7. Sketch by ALENIA SPAZIO Surface Habitats Innovative concepts under study Use of local materials Cavity in the planetary soil + Covering heap

8. Radiation environment

9. Vehicle concepts Surface habitats Astronaut Electromagnetic processes + Hadronic processes Radiation protection with • Model the radiation spectrum according to current standards • Galactic cosmic rays, Solar particle events • Physics • Select appropriate models from the Geant4 Toolkit • Verify the accuracy of the physics models • Distinguish e.m. and hadronic contributions to the dose • Geometrical configurations • Model essential characteristics for dosimetry studies • Model complex geometries of spacecrafts in detail • Evaluate energy deposit/dose in shielding configurations • various shielding materials and thicknesses

10. Geant4 EM Physics Models • Verification of the Geant4 e.m. physics processes with respect to protocol data (NIST reference data, ICRU Report 49) Geant4 electromagnetic physics models are accurate Compatible with NIST data within NIST accuracy (LowE p-value > 0.9) “Comparison of Geant4 electromagnetic physics models against the NIST reference data” IEEE Transactions on Nuclear Science, vol. 52 (4), pp. 910-918, 2005 Optimal selection • Geant4 Low Energy Package for p, a, ions and their secondaries • Geant4 Standard Package for positrons

11. Geant4 Hadronic Physics • Complementary and alternative models • Parameterised, data driven and theory driven models • The most complete hadronic simulation kit available on the market • Models for p and a • Hadronic models for ions in progress Intrinsic complexity of hadronic physics Ample choice of models Composition of different models over an extended energy range to cover the spectrum of galactic cosmic rays and solar particle events

12. Lateral profile 6MV – 10x10 field – 50mm depth Percent dose Distance (mm) 30 cm Z Dosimetry • The Astronaut is approximated as a phantom • a waterbox, sliced along the longitudinal axis to evaluate particle penetration in the body • the transversal size is optimized to contain the shower generated by the interacting particles • the longitudinal size is a “realistic” human body thickness • The phantom is the volume where the energy deposit is collected • The energy deposit is given by the primary particles and all the secondaries created IMRT Treatment Head

13. e.m. physics + Bertini set 2.15 cm Al 5 cm water e.m. physics only 10 cm water 10 cm polyethylene 10 cm water 4 cm Al Doubling the shielding thickness decreases the energy deposit by ~10% 10 cm water 5 cm water rigid/inflatable habitats are equivalent shielding materials

14. SIH Shelter Strategy against SPE Energy deposit (MeV) with respect to the depth in the phantom (cm) A shelter with additional water shielding (75 cm thickness) The shelter shields • ~ 50% of the dose by GCR p • ~ 67 % of the dose by GCR α escaping the main shielding 99.7% of the SPE spectrum is shielded • SPE p and a • with E > 130 MeV/nucl reach the shelter • with E > 400 MeV/nucl reach the phantom • (i.e. < 0.3% of the entire spectrum)

15. x = 0 - 3 m roof thickness Planetary surface habitats Moon as an intermediate step in the exploration of Mars Habitat built out of moon soil 4 cm Al 4 cm Al GCR p GCR α vacuum x e.m. + hadronic physics (Bertini set) Habitat moon soil Energy deposit (GeV) in the phantom vs roof thickness (m) Phantom A log of moon soil is as effective as Al shielding, or even better

16. Dosimetry with Geant4 • All the previous results are novel radiation protection applications of Geant4 • first quantitative evaluation of space radiation effects for interplanetary manned missions based on 3D Monte Carlo calculations • first quantitative comparison of innovative shielding concepts w.r.t. conventional solutions • Key Geant4 features • wide spectrum of physics coverage • precise, quantitatively validated physics models selected as the most appropriate for the application • accurate description of materials • Same key features as indosimetry for medical applications

17. A major concern in radiation protection is the dose accumulated in organs at risk Anthropomorphic Phantoms • Development of anthropomorphic phantom models for Geant4 • evaluate dose deposited in critical organs • Original approach • analytical and voxel phantoms in the same simulation environment • mix & match • facilitated by the OO technology • First release December 2005 • G. Guerrieri, Thesis, Univ. Genova, Oct. 2005

18. Sound software technology and rigorous software process Analytical phantoms Geant4 CSG, BREPS solids Voxel phantoms Geant4 parameterised volumes GDML for geometry description storage

19. Geant4 analytical phantoms 1 skull 2 thyroid 3 spine 4 lungs 5 breast 6 heart 7 liver 8 stomach 9 spleen 10 kidneys 11 pancreas 12 intestine 13 uterus and ovaries 14 bladder 15 womb 16 leg bones 17 arm bones Current implementation ORNL and MIRD5 phantoms Male and Female Geant4 analytical phantom ORNL model, female

20. G4Lady

21. 5 cm water shielding Skull Upper spine Lower spine Arm bones Leg bones Womb Stomach Upper intestine Lower intestine Liver Pancreas Spleen Kidneys Bladder Breast Overies Uterus 10 cm water shielding Skull Upper spine Lower spine Arm bones Leg bones Womb Stomach Upper intestine Lower intestine Liver Pancreas Spleen Kidneys Bladder Breast Overies Uterus Application Dose calculation in critical organs Effects of external shielding Self-body shielding

22. Total Body Irradiation • TBI is used as a method of preparation for bone marrow transplantation for leukemias and lymphomas • Low dose TBI is sometimes used to treat disorders of the blood cells such as low grade lymphoma and does not require bone marrow transplant or stem cells • In TBI, the dose calculation is based on dosimetry using a phantom opens new ground for precise dose calculation and TBI optimisation

23. Radfet #2 S300/50 Radfet #4 G300/50 D300/50 Bulk D690/15 Radfet #1#3 DG690/15 G690/15 S690/15 Bulk Diode DG300/50 Dosimetry with Geant4 Precise physics Rigorous validation Space science Radiotherapy Effects on components Multi-disciplinary application environment

24. Geant4 Symposium 2015 DNA Study of radiation damage at the cellular and DNA level

25. http://www.ge.infn.it/geant4/dna

26. Geant4-based “sister” activity to the Geant4 Low-Energy Electromagnetic Working Group Follows the same rigorous software standards International (open) collaboration ESA, INFN (Genova, Torino), IN2P3 (CENBG, Univ. Clermont-Ferrand), Univ. of Lund Simulation of nano-scale effects of radiation at the DNA level Various scientific domains involved medical, biology, genetics, physics, software engineering Multiple approaches can be implemented with Geant4 RBE parameterisation, detailed biochemical processes, etc. First phase: 2000-2001 Collection of user requirements & first prototypes Second phase: started in 2004 Software development & release DNA The concept of “dose” fails at cellular and DNA scales It is desirable to gain an understanding to the processes at all levels (macroscopic vs. microscopic)

27. Biological models in Geant4 Relevance for space: astronaut and aircrew radiation hazards

28. Biological processes Biologicalprocesses Physicalprocesses Known, available Unknown, not available Courtesy A. Brahme (KI) E.g. generation of free rad icals in the cell Chemicalprocesses Courtesy A. Brahme (Karolinska Institute)

29. Cellular level Theories and models for cell survival • TARGET THEORY MODELS • Single-hit model • Multi-target single-hit model • Single-target multi-hit model • MOLECULAR THEORY MODELS • Theory of radiation action • Theory of dual radiation action • Repair-Misrepair model • Lethal-Potentially lethal model in progress Analysis & Design Implementation Test Critical evaluation of the models done Experimental validation of Geant4 simulation models Requirements Problem domain analysis

30. S = e –p ( αD + ßD ) 2 2 S = S0 e - k (ξD + D ) NPL S = exp[ - NTOT[1 + ]ε] ε (1 – e- εBAtr) S = e-q1D [ 1- (1- e-qnD)n ] S = e-αD[1 + (αDT / ε)]ε S= e-D / D0 REVISED MODEL S = 1- (1- e-qD)n In progress: calculation of model parameters from clinical data S = e-αD[1 + (αD / ε)]εΦ S = e-ηAC D - ln[ S(t)] = (ηAC +ηAB) D – ε ln[1 + (ηABD/ε)(1 – e-εBA tr)] - ln[ S(t)] = (ηAC +ηAB e-εBAtr ) D + (η2AB/2ε)(1 – e-εBA tr)2 D2]

31. DNA level Low Energy Physics extensions • Current Geant4 low energy electromagnetic processes: down to 250/100 eV (electrons and photons) • not adequate for application at the DNA level • Specialised processes down to the eV scale • at this scale physics processes depend on material, phase etc. • some models exist in literature (Dingfelder et al., Emfietzoglou et al. etc.) • In progress: Geant4 processes in water at the eV scale • Status: first release in December 2005

32. Scenario for Mars (and hospitals) Geant4 simulation with biological processes at cellular level (cell survival, cell damage…) Geant4 simulation treatment source + geometry from CT image or anthropomorphic phantom Geant4 simulation space environment + spacecraft, shielding etc. + anthropomorphic phantom Dose in organs at risk Oncological risk to astronauts/patients Risk of nervous system damage Phase space input to nano-simulation Geant4 simulation with physics at eV scale + DNA processes

33. for medicine • Macroscopic • calculation of dose • already feasible with Geant4 • develop useful associated tools • Cellular level • cell modelling • processes for cell survival, damage etc. • DNA level • DNA modelling • physics processes at the eV scale • processes for DNA strand breaking, repair etc. Complexity of software, physics and biology addressed with an iterative and incremental software process Parallel development at all the three levels (domain decomposition)

34. Exotic Geant4 applications… FAO/IAEA International Conference on Area-Wide Control of Insect Pests: Integrating the Sterile Insect and Related Nuclear and Other Techniques Vienna, May 9-13, 2005 K. Manai, K. Farah, A.Trabelsi, F. Gharbi and O. Kadri (Tunisia) Dose Distribution and Dose Uniformity in Pupae Treated by the Tunisian Gamma Irradiator Using the GEANT4 Toolkit

35. Thanks • Riccardo Capra, Susanna Guatelli, Giorgio Guerrieri, Barbara Mascialino, Michela Piergentili (INFN Genova) • Petteri Nieminen (ESA) • Alenia Spazio (Torino) • Sébastien Incerti, Philippe Moretto (CENBG) • Ziad Francis, Gérard Montarou (Univ. Clermont-Ferrand) • Stéphane Chauvie (INFN Torino) • Joseph Perl (SLAC) • Thanks to many Geant4 users worldwide, even if not all their Geant4 applications in medicine were mentioned in this presentation