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Geant4 Space Workshop DNA

VIEWS: 48 PAGES: 25

									 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

								
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