Geant4 Space Workshop - DNA by lo047q

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									          Applications in Medicine
                                      Maria Grazia Pia
                                   INFN Sezione di Genova



                                 Symposium on Geant4 Applications

                                9th ICATPP Conference
                                   Como, 17-21 October 2005
Maria Grazia Pia, INFN Genova
                                  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
     Thanks to Simone Giani       KAROLINSKA (Sweden) – by A.Brahme
 for organizing this symposium!   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
Maria Grazia Pia, INFN Genova     IMPERIAL COLLEGE (UK) – by M.Ellis
                                                Medical applications
                                                                                        PET, SPECT



                                                                                                                     Courtesy of GATE Collaboration




Courtesy of B. Mascialino et al., INFN Genova

  Radiotherapy with                               Courtesy of P. Cirrone et al., INFN LNS

external beams, IMRT                                        Hadrontherapy

                                   Radiation                              Brachytherapy                  Courtesy of S. Guatelli et al,. INFN Genova
                                   Protection




Maria Grazia Pia, INFN Genova                                                Courtesy of L. Beaulieu et al., Laval
                      Courtesy of J. Perl, SLAC
                   Mars and Leukemia

                                  Maria Grazia Pia
                                INFN Sezione di Genova


                      Symposium on Geant4 Applications
                          9th ICATPP Conference
                                Como, 17-21 October 2005
Maria Grazia Pia, INFN Genova
 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
Maria Grazia Pia, INFN Genova
 SIH - Simplified Inflatable Habitat              Vehicle concepts
                                                         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

Materials and thicknesses by ALENIA SPAZIO      Rebundant bladder
                                                  - Polyethylene, polyacrylate, EVOH, kevlar, nomex

  Maria Grazia Pia, INFN Genova
   Surface Habitats



Innovative concepts under study
      Use of local materials
     Cavity in the planetary soil
                  +
           Covering heap




                                    Sketch by ALENIA SPAZIO

Maria Grazia Pia, INFN Genova
Radiation environment




Maria Grazia Pia, INFN Genova
Radiation protection with
 Model the radiation spectrum according to current standards
  – Galactic cosmic rays, Solar particle events


  Geometrical configurations                                         Vehicle concepts
   – Model essential characteristics for dosimetry studies            Surface habitats
   – Model complex geometries of spacecrafts in detail                   Astronaut

 Physics
   – Select appropriate models from the Geant4 Toolkit         Electromagnetic processes
   – Verify the accuracy of the physics models                   + Hadronic processes
   – Distinguish e.m. and hadronic contributions to the dose


 Evaluate energy deposit/dose in shielding configurations
  – various shielding materials and thicknesses

Maria Grazia Pia, INFN Genova
   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

Maria Grazia Pia, INFN Genova
   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

 Maria Grazia Pia, INFN Genova
                                  Dosimetry
  The Astronaut is approximated as a phantom
    – a water box, 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                          30 cm
   – The energy deposit is given by the primary particles and all the secondaries created          Z
                                                          Lateral profile
                                                  6MV – 10x10 field – 50mm depth
                                                                                   IMRT Treatment Head
                                   Percent dose




Maria Grazia Pia, INFN Genova                               Distance (mm)
                                               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
   Strategy against SPE
                                                           Energy deposit (MeV) with respect to the
         A shelter with additional                                      depth in the phantom (cm)

             water shielding
            (75 cm thickness)

                                     SIH




                                            99.7% of the
                                 Shelter
                                           SPE spectrum
                                             is shielded
SPE p and a                                            The shelter shields
 with E > 130 MeV/nucl reach the shelter                  ~ 50% of the dose by GCR p
 with E > 400 MeV/nucl reach the phantom                  ~ 67 % of the dose by GCR α
  (i.e. < 0.3% of the entire spectrum)                 escaping the main shielding
 Maria Grazia Pia, INFN Genova
   Planetary surface habitats
Moon as an intermediate step in                                              4 cm Al
   the exploration of Mars

 Habitat built out of moon soil
                                                                             4 cm Al




     x = 0 - 3 m roof thickness
                                                   GCR p
                         vacuum                    GCR α
        x




      Habitat                                    e.m. + hadronic physics (Bertini set)
                            moon
                             soil

                  Phantom           Energy deposit (GeV) in the phantom vs roof thickness (m)


                                        A log of moon soil is as effective as
                                            Al shielding, or even better
Maria Grazia Pia, INFN Genova
   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 in dosimetry for medical applications

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
                                          – mix & match
                                          – facilitated by the OO technology

                                         First release December 2005
                                          – G. Guerrieri, Thesis, Univ. Genova, Oct. 2005



Maria Grazia Pia, INFN Genova
Sound software technology
           and
rigorous software process




     Analytical phantoms
  Geant4 CSG, BREPS solids
         Voxel phantoms
Geant4 parameterised volumes


                  GDML
for geometry description storage


 Maria Grazia Pia, INFN Genova
                 Geant4 analytical phantoms

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

  Maria Grazia Pia, INFN Genova
                                G4Lady




Maria Grazia Pia, INFN Genova
Maria Grazia Pia, INFN Genova
                                       Self-body shielding
                                                                                                                                                   Application




                                   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
   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
Maria Grazia Pia, INFN Genova
                     Dosimetry with Geant4
                                 Precise physics
                                Rigorous validation




     Space science               Radiotherapy        Effects on components




Maria Grazia Pia, INFN Genova
                                 Multi-disciplinary application environment
                    Geant4 Symposium 2015




                                       DNA
                                Study of radiation damage at
                                 the cellular and DNA level


Maria Grazia Pia, INFN Genova
http://www.ge.infn.it/geant4/dna




  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)
      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
Maria Grazia Pia, INFN Genova
Biological models in Geant4
Relevance for space:
astronaut and aircrew radiation hazards


 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
 Multi-target single-hit model
                                        in progress
 Single-target multi-hit model

MOLECULAR THEORY MODELS
 Theory of radiation action
 Theory of dual radiation action
 Repair-Misrepair model                Analysis & Design
 Lethal-Potentially lethal model       Implementation
                                        Test

    Critical evaluation of the models

done
                                                      Experimental validation of
        Requirements                                  Geant4 simulation models
   Problem domain analysis
  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              calculation 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
        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


Maria Grazia Pia, INFN Genova
Scenario
for Mars (and hospitals)                                 Geant4 simulation
                                                            with biological
                                                        processes at cellular
    Geant4 simulation                                    level (cell survival,
    treatment source
   space environment               Dose in organs          cell damage…)
             +                        at risk
 geometry from CT image
 spacecraft, shielding etc.
             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
                                      for medicine

       Macroscopic
         – 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
         – processes for DNA strand breaking, repair etc.


Maria Grazia Pia, INFN Genova
   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

Maria Grazia Pia, INFN Genova
   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



Maria Grazia Pia, INFN Genova

								
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