Geant4 for Microdosimetry

1. DNA R. Capra, S. Chauvie, Z. Francis, S. Guatelli, S. Incerti, B. Mascialino, Ph. Moretto, G. Montarou, P. Nieminen, Maria Grazia Pia Geant4 for Microdosimetry MICROS 2005 Venezia, 13-18 November 2005

2. Born from the requirements of large scale HEP experiments Object Oriented Toolkit for the simulation of particle interactions with matter • Widely used not only in HEP • Space science and astrophysics • Medical physics, medical imaging • Radiation protection • Accelerator physics • Pest control, food irradiation • Landmining, security • etc. • Technology transfer also… An experiment of distributed software production and management An experiment of application of rigoroussoftware engineering methodologies andObject Oriented technology to particle physics environment R&D phase: RD44, 1994 - 1998 1st release: December 1998 2 new releases/year since then

3. Geant4 architecture Interface to external products w/o dependencies Domain decomposition hierarchical structure of sub-domains Uni-directional flow of dependencies in a nutshell • Rigorous software engineering • spiral software process • object oriented methods • quality assurance • use of standards • Geometry • multiple solid representations handled through the same abstract interface (CSG, STEP compliant solids, BREPs) • Simple placements, parameterised volumes, replicas, assembly-volumes etc. • Boolean operations on solids • Physics independent from tracking • Subject to rigorous, quantitative validation • Electromagnetic physics • Standard, Low-Energy, Muon, Optical etc. • Hadronic physics • Parameterised, data-driven, theory-driven models • Interactive capabilities • visualisation, UI/GUI • multiple drivers to external systems w/o introducing dependencies

4. Geant4 Collaboration Major physics laboratories: CERN, KEK, SLAC, TRIUMF, TJNL European Space Agency: ESA National Institutes: INFN, IN2P3, PPARC Universities: Budker Inst., Frankfurt, Karolinska Inst., Helsinki, Lebedev Inst., LIP, Lund, Northeastern etc. ~80 members MoU based Development, Distribution and User Support of Geant4

5. 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 • Wide spectrum of physics coverage, variety of models • Precise, quantitatively validated physics • Accurate description of geometry and materials Multi-disciplinary application environment Space science Radiotherapy Effects on components

6. Courtesy of L. Beaulieu et al., Laval Radiation Protection Courtesy of J. Perl, SLAC Dosimetry in MedicalApplications Courtesy of F. Foppiano et al., IST Genova Radiotherapy with external beams, IMRT Courtesy of P. Cirrone et al., INFN LNS Hadrontherapy Courtesy of S. Guatelli et al,. INFN Genova Brachytherapy

7. Lateral profile 6MV – 10x10 field – 50mm depth Percent dose Distance (mm) Precise dose calculation Geant4 Low Energy Electromagnetic Physics package • Electrons and photons (250/100 eV < E < 100 GeV) • Models based on the Livermore libraries (EEDL, EPDL, EADL) • Penelope models • Hadrons and ions • Free electron gas + Parameterisations (ICRU49, Ziegler) + Bethe-Bloch • Nuclear stopping power, Barkas effect, chemical formulae effective charge etc. • Atomic relaxation • Fluorescence, Auger electron emission, PIXE Kolmogorov-Smirnov Test IMRT Treatment Head

8. Dosimetry: protons and ions agreement with data better than 3% Electromagnetic only Inventory of Geant4 hadronic models

9. Radiation protection for interplanetary manned missions

10. 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

11. 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 Analytical phantoms Geant4 CSG, BREPS solids Voxel phantoms Geant4 parameterised volumes GDML for geometry description storage

12. 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 Radiation exposure of astronauts Dose calculation in critical organs Effects of external shielding Self-body shielding

13. So why not describing DNA? DNA So what about mutagenesis as a process? Geometry objects (solids, logical volumes, physical volumes) are handled transparently by Geant4 kernel through abstract interfaces Processes are handled transparently by Geant4 kernel through an abstract interface Object Oriented technology + Geant4 architecture

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

15. “Sister” activity to Geant4 Low-Energy Electromagnetic Physics 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 & public, open source 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)

16. Multiple domains in the same software environment • Macroscopic level • 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 • bio-chemical processes • processes for DNA damage, 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)

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

18. 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)

19. 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 Geant4 approach: variety of models all handled through the same abstract interface in progress Critical evaluation of the models Analysis & Design Implementation Test Requirements Problem domain analysis Experimental validation of Geant4 simulation models

20. - D/DC n! PSURV(q,b,n,D) = B(b) (e-qD)(n-b) (1- e-qD)b b! (n -b)! S = e-αR [1 + ( αS / αR -1)e ] D – ß D 2 S= e-ßD Target theory models Extension of single-hit model No hits: cell survives One or more hits: cell dies Multi-target single-hit model Cell survival equations based on model-dependent assumptions Single-hit model S(ρ,Δ) = PSURV(ρ0, h=0, Δ) = (1- ρ0)Δ= exp[Δ ln (1- ρ0)] Single-target multi-hit model • No assumption on: • Time • Enzymatic repair of DNA Joiner & Johns model two hits

21. Molecular models for cell death More sophisticated models Theory of dual radiation action Molecular theory of radiation action (linear-quadratic model) Kellerer and Rossi (1971) Chadwick and Leenhouts (1981) Lethal-potentially lethal model Repair or misrepair of cell survival Tobias et al. (1980) Curtis (1986)

22. 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: evaluation 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]

23. DNA level Low Energy Physics extensions • Specialised processes down to the eV scale • at this scale physics processes depend on material, phase etc. • In progress: Geant4 processes in water at the eV scale, release winter 2006 • Details: see poster presentation • Processes for other material than water to follow

24. Scenario for Mars (and Earth…) Geant4 simulation with biological processes at cellular level (cell survival, cell damage…) Dose in organs at risk Geant4 simulation space environment + spacecraft, shielding etc. + anthropomorphic phantom Geant4 simulation treatment source + geometry from CT image or anthropomorphic phantom 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

25. Conclusions • Geant4 offers powerful geometry and physics modelling in an advanced computing environment • Wide spectrum of complementary and alternative physics models • Multi-disciplinary applications of dosimetry simulation • Precision of physics, validation against experimental data • Geant4-DNA: extensions for microdosimetry • physics processes at the eV scale • biological models • Multiple levels addressed in the same simulation environment • conventional dosimetry • processes at the cellular level • processes at DNA level • OO technology in support of physics versatility: openness to extension, without affecting Geant4 kernel