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Riccardo Capra 1 , Stéphane Chauvie 2 ,

The. Collaboration . Riccardo Capra 1 , Stéphane Chauvie 2 , Ziad Francis 3 , Sebastien Incerti 4 , Barbara Mascialino 1 , Gerard Montarou 3 , Philippe Moretto 4 , Petteri Nieminen 5 , Maria Grazia Pia 1. 1 INFN Sezione di Genova (Italy)

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Riccardo Capra 1 , Stéphane Chauvie 2 ,

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  1. The Collaboration Riccardo Capra1, Stéphane Chauvie2, Ziad Francis3, Sebastien Incerti4, Barbara Mascialino1, Gerard Montarou3, Philippe Moretto4, Petteri Nieminen5, Maria Grazia Pia1 1 INFN Sezione di Genova (Italy) 2 Azienda Ospedaliera Santa Croce e Carle Cuneo; INFN Sezione di Torino (Italy) 3 Université Blaise Pascal, Laboratoire de Physique Corpusculaire; IN2P3 (France) 4 Centre d’Etudes Nucléaires de Bordeaux-Gradignan and Université Bordeaux; IN2P3 (France) 5 European Space Agency (The Netherlands)

  2. Radiobiological models implementation in Toolkit 14th Symposium on Microdosimetry November 13-18, 2005 – Venezia, Italy

  3. Abstract A project is in progress to extend the Geant4 simulation toolkit to model the effects of radiation with biological systems, both at cellular and DNA level. For the first time a general-purpose Monte Carlo system is equipped with functionality specific to radiobiological simulations. The object oriented technology adopted by Geant4 allows providing an ample set of models to simulate the response of a cell line to irradiation, leaving the option to users to choose among them the most appropriate ones for their simulation study. The project follows an iterative and incremental software process; the first component implemented describes a primary biological endpoint: the fractional survival of a population of cells irradiated with photons or charged particles. It provides the user the option to choose among a wide set of cell survival models, such as models based on the target theory of cell killing, the repair-misrepair model, the lethal-potentially lethal model, and the Scholz and Kraft model. The flexible design adopted makes it open to further extension to implement other cell survival models. We present the architecture of the new Geant4 component for radiobiological modeling, the detailed design of the cell survival models implemented and preliminary results of application in some specific cell lines. The simulation tool developed for the study of radiation interaction with biological matter would have a wide domain of application in several fields: from oncological radiotherapy to the radiation protection of astronauts.

  4. is a simulation toolkit for the simulation of the passage of particles through matter. object-oriented design and component architecture allows the extension of the toolkit functionality without affecting its kernel. A project is in progress to extend the simulation toolkit to model the effects of radiation with biological systems, both at cellular and DNA level. For the first time a general-purpose Monte Carlo system is equipped with functionality specific to radiobiological simulations.

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

  6. Collection of User Requirements Biologicalprocesses Physicalprocesses Known, available Process requirements Unknown, not available E.g. generation of free rad icals in the cell Chemicalprocesses Courtesy Nature User requirements on geometry and visualisation

  7. Software process guidelines • Unified Process, specifically tailored to the project • practical guidance and tools from the RUP • both rigorous and lightweight • mapping onto ISO 15504 • Incremental and iterative life-cycle mandatory in such a complex, evolving research field • Realistic, concrete objectives • code release with usable functionality First component fractional survival of a population of cells irradiated with photons or charged particles SPIRAL APPROACH

  8. Biological processes • Complexity • Multiple disciplines involved • physics • chemistry • biology • Still object of active research • not fully known • no general models, only partial/empirical ones Courtesy A. Brahme (KI) Courtesy A. Brahme (Karolinska Institute)

  9. Uncertainties Particles / Fluence rates LOW • Physics • Radiobiology • Extrapolations to human beings MODERATE Shielding LARGE (cells, tissues, animals) Acute exposure LARGE Chronic exposure LARGER Space radiation effects

  10. Scope • Goal: provide capabilities to study the biological effects of radiation at multiple levels • Macroscopic • calculation of dose • already feasible with Geant4 • develop useful associated tools • Cellular level • cell modelling • processes for cell survival, transformation etc. • DNA level • DNA modelling • physics processes at the eV scale • processes for DNA strand breaks, chromosome aberrations etc. Complexity of software, physics and biology addressed with an iterative and incremental software process Parallel development at all the three levels (domain decomposition)

  11. Different biological endpoints Cell survival Cell transformation Chromosome aberrations Sublethal damage repair Cell cycle Temperature Fractionation Dose rate effect Inverse dose rate effect Low dose hypersensitivity Courtesy Hall Courtesy Blakely

  12. Cellular level Models for cell survival • SURVIVAL MODELS • Single-hit model • Multi-target single-hit model • Single-target multi-hit model • Theory of radiation action • Theory of dual radiation action • Repair-Misrepair model • Lethal-Potentially lethal model • Scholz-Kraft model in progress Analysis & Design Implementation Test Critical evaluation of the models future done Experimental validation of Geant4 simulation models Requirements Problem domain analysis The flexible design adopted makes it open to further extension to implement other cell survival models.

  13. Primary and secondary particles deposit energy PROBLEM: Describe the surviving fraction of cells starting from alternative theoretical models - Repair-misrepair model - Lethal – potentially lethal model - Scholz-Kraft model - Target theory models - Radiation action model - Dual radiation action model Incident radiation (electromagnetic and hadronic interactions) Cell line Retrieve the dose in the cell Retrieve the biological outcome of the targeted cells Model the cell in terms of geometry and materials Describe the surviving fraction On the basis of the model selected Cell nucleus Cell cytoplasm

  14. 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 Elastic scattering Ionisation processes Electrons exchange Excitation

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

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