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Geant4 for Microdosimetry R. Capra, S. Chauvie, Z. Francis, S. Guatelli, S. Incerti, B. Mascialino, Ph. Moretto, G. Montarou, P. Nieminen, Maria Grazia Pia DNA MICROS 2005 Venezia, 13-18 November 2005 Maria Grazia Pia, INFN Genova Born from the requirements of Object Oriented Toolkit for large scale HEP experiments the simulation of particle Widely used not only in HEP interactions with matter • Space science and astrophysics • Medical physics, medical imaging also… • Radiation protection • Accelerator physics An experiment of • Pest control, food irradiation distributed software production • Landmining, security and management • etc. • Technology transfer An experiment of application of rigorous software engineering methodologies R&D phase: RD44, 1994 - 1998 and Object Oriented technology to particle physics environment 1st release: December 1998 2 new releases/year since then Maria Grazia Pia, INFN Genova Geant4 architecture in a nutshell Rigorous software engineering – spiral software process – object oriented methods Interface to Domain – quality assurance external decomposition – use of standards products w/o Geometry dependencies – multiple solid representations handled through the hierarchical same abstract interface (CSG, STEP compliant solids, BREPs) structure of sub- – Simple placements, parameterised volumes, domains replicas, assembly-volumes etc. – Boolean operations on solids Physics independent from tracking Uni-directional Subject to rigorous, quantitative validation flow of Electromagnetic physics dependencies – 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 Maria Grazia Pia, INFN Genova introducing dependencies ~80 members Geant4 Collaboration MoU based Development, Distribution and User Support of Geant4 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. Maria Grazia Pia, INFN Genova 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 Maria Grazia Pia, INFN Genova Dosimetry in Medical Applications Courtesy of F. Foppiano et al., IST Genova Radiotherapy with Courtesy of P. Cirrone et al., INFN LNS external beams, IMRT Hadrontherapy Courtesy of S. Guatelli et al,. INFN Genova Brachytherapy Radiation Protection Maria Grazia Pia, INFN Genova Courtesy of J. Perl, SLAC Courtesy of L. Beaulieu et al., Laval 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 Lateral profile 6MV – 10x10 field – 50mm depth Kolmogorov-Smirnov Test IMRT Treatment Head range D p-value Percent dose -84 -60 mm 0.39 0.23 -59 -48 mm 0.27 0.90 -47 47 mm 0.43 0.19 48 59 mm 0.30 0.82 84 Grazia 0.10 60 Maria mm Pia, 0.40 Genova INFN Distance (mm) Dosimetry: protons and ions agreement with data WHOLE PEAK Cramer – Anderson – better than 3% (N1=149 N2=66) von Mises test Darling test Test statistics 0.06 0.499375 p-value 0.79 0.747452 Electromagnetic only 0.52 0.443831 Inventory of Geant4 hadronic models Maria Grazia Pia, INFN Genova Radiation protection for interplanetary manned missions Maria Grazia Pia, INFN Genova Doubling the shielding thickness decreases the energy deposit by ~10% 10 cm water 5 cm water rigid/inflatable habitats are equivalent 2.15 cm Al e.m. physics + Bertini set shielding 5 cm water materials e.m. 10 cm water 4 cm Al physics 10 cm water only 10 cm polyethylene Maria Grazia Pia, INFN Genova A major concern in radiation protection is the dose accumulated in organs at risk Development of anthropomorphic Anthropomorphic phantom models for Geant4 Phantoms – 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 Maria Grazia Pia, INFN Genova for geometry description storage Maria Grazia Pia, INFN Genova of astronauts Self-body shielding Radiation exposure Effects of external shielding Dose calculation in critical organs Skull Skull Upper spine Upper spine Lower spine Lower spine Arm bones Arm bones Leg bones Leg bones Womb Womb Stomach Stomach Upper intestine Upper intestine Lower intestine Lower intestine Liver Liver Pancreas Pancreas Spleen Spleen Kidneys 5 cm water shielding Kidneys 10 cm water shielding Bladder Bladder Breast Breast Overies Overies Uterus Uterus Geometry objects (solids, logical volumes, physical volumes) are handled transparently by So why not describing Geant4 kernel through DNA? abstract interfaces Processes are handled transparently by Geant4 kernel So what about through an mutagenesis as a abstract interface process? DNA Object Oriented technology + Geant4 architecture Maria Grazia Pia, INFN Genova Biological models in Geant4 Relevance for space: astronaut and aircrew radiation hazards Maria Grazia Pia, INFN Genova The concept of “dose” fails at cellular and DNA scales It is desirable to gain an understanding DNA to the processes at all levels (macroscopic vs. microscopic) “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 Maria Grazia Pia, INFN Genova Multiple domains in the same software environment Macroscopic level – calculation of dose Complexity of – already feasible with Geant4 – develop useful associated tools software, physics and biology addressed with an iterative and Cellular level incremental software process – cell modelling – processes for cell survival, damage etc. Parallel development DNA level at all the three levels – DNA modelling (domain decomposition) – physics processes at the eV scale – bio-chemical processes – processes for DNA damage, repair etc. Maria Grazia Pia, INFN Genova http://www.ge.infn.it/geant4/dna Maria Grazia Pia, INFN Genova Biological processes Physical Biological processes processes Known, available Unknown, not available Courtesy A. Brahme (KI) E.g. generation Chemical of free rad icals processes in the cell Courtesy A. Brahme Maria Institute) (Karolinska Grazia Pia, INFN Genova Cellular level Theories and models for cell survival TARGET THEORY MODELS Single-hit model Geant4 approach: variety of Multi-target single-hit model models all handled through Single-target multi-hit model the same abstract interface MOLECULAR THEORY MODELS Theory of radiation action Theory of dual radiation action in progress Repair-Misrepair model Lethal-Potentially lethal model Critical evaluation of the models Analysis & Design Implementation Test Requirements Problem domain analysis Experimental validation of Geant4 simulation models Maria Grazia Pia, INFN Genova Target theory models No hits: cell survives Extension of single-hit model One or more hits: cell dies Cell survival equations Multi-target Single-hit based on single-hit model-dependent model model assumptions n! PSURV(q,b,n,D) = B(b) (e-qD)(n-b) (1- e-qD)b S(ρ,Δ) = PSURV (ρ0, h=0, Δ) = (1- ρ0)Δ = exp[Δ ln (1- ρ0)] b! (n -b)! No assumption on: Single-target • Time multi-hit Joiner & Johns • Enzymatic repair of DNA model model 2 - D/DC S= e-ßD two hits S= e-αR [1 + ( αS / αR -1) e ]D–ßD Maria Grazia Pia, INFN Genova Molecular models for cell death More sophisticated models Molecular theory Theory of dual of radiation action radiation action (linear-quadratic model) Chadwick and Leenhouts (1981) Kellerer and Rossi (1971) Repair or misrepair Lethal-potentially of cell survival lethal model Tobias et al. (1980) Curtis (1986) Maria Grazia Pia, INFN Genova TARGET SINGLE-HIT THEORY S= e-D / D0 REVISED MODEL TARGET MULTI-TARGET THEORY SINGLE-HIT S = 1- (1- e-qD)n S = e-q1D [ 1- (1- e-qn D)n ] MOLECULAR RADIATION ACTION S = e –p ( αD + ßD 2 ) THEORY In progress: MOLECULAR DUAL RADIATION 2 evaluation of S = S0 e - k (ξ D + D ) THEORY ACTION model MOLECULAR REPAIR-MISREPAIR parameters THEORY LIN REP / QUADMIS S = e-αD[1 + (αDT / ε)]ε from clinical MOLECULAR REPAIR-MISREPAIR data THEORY LIN REP / MIS S = e-αD[1 + (αD / ε)]εΦ MOLECULAR LETHAL-POTENTIALLY NPL THEORY LETHAL S = exp[ - NTOT[1 + ε (1 – e- εBAtr) ]ε ] MOLECULAR LETHAL-POTENTIALLY THEORY LETHAL – LOW DOSE S = e-ηAC D MOLECULAR LETHAL-POTENTIALLY - ln[ S(t)] = (ηAC + ηAB) D – ε ln[1 + (ηABD/ε)(1 – e-εBA tr)] THEORY LETHAL – HIGH DOSE MOLECULAR LETHAL-POTENTIALLY LETHAL – LQ APPROX - ln[ S(t)] = (ηAC + ηAB e-εBAtr ) D + (η2AB/2ε)(1 – e-εBA tr)2 D2] THEORY Maria Grazia Pia, INFN Genova 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 Electrons Protons (H+) Hydrogen (H) Alpha (He++) He+ He Brenner (7.5 - 200 eV) Elastic Emfietzoglou (> 200 ev) Negligible effect Negligible effect Negligible effect Negligible effect Negligible effect Emfietzoglou Miller and Green Miller and Green Miller and Green Miller and Green Excitation Born (7 ev – 10 keV) Born (100 eV – 10 MeV) Negligible effect (1 keV – 15 MeV) (1 keV – 15 MeV) (1 keV – 15 MeV) Not pertinent to this Dingfelder Not pertinent to this Not pertinent to this Charge decrease particle (100 eV – 2 MeV) particle In progress In progress particle Miller and Green Not pertinent to this Not pertinent to this Not pertinent to this Charge increase particle particle Dingfelder particle In progress In progress (0.1 Kev – 100 MeV) Rudd (0.1 - 500 keV) Ionization In progress In progress (> 500 keV) Rudd (0.1 – 100 MeV) In progress In progress In progress Maria Grazia Pia, INFN Genova Scenario Geant4 simulation for Mars (and Earth…) with biological processes at cellular level (cell survival, Geant4 simulation Dose in organs cell damage…) space environment treatment source at risk + spacecraft, shielding etc. 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 + Maria Grazia Pia, INFN Genova DNA processes 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 Maria Grazia Pia, INFN Genova
"Geant4 Space Workshop DNA"