Geant4 Space Workshop - DNA

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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 dEtudes Nucléaires de
Bordeaux-Gradignan and Université Bordeaux IN2P3
(France) 5 European Space Agency (The Netherlands)
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14th Symposium on Microdosimetry November 13-18,
2005 Venezia, Italy
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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.
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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.
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Biological models in Geant4 Relevance for
space astronaut and aircrew radiation hazards
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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
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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
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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)
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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
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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)
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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
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Models for cell survival
Cellular level

• 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.
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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
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Low Energy Physics extensions
DNA level

• 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
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http//www.ge.infn.it/geant4/dna