Maria Grazia Pia, INFN Genova
forfor MicrodosimetryMicrodosimetry
CECAM WorkshopLyon, 3-6 December 2007
DNADNA
Maria Grazia PiaINFN Genova
S. Chauvie (Cuneo Hospital and INFN), S. Incerti and Ph. Moretto (CENBG)
Partly funded by
Maria Grazia Pia, INFN GenovaCourtesy Borexino
Courtesy H. Araujo and A. Howard, IC London
ZEPLIN III
Courtesy CMS Collaboration
Courtesy ATLAS Collaboration
Courtesy K. Amako et al., KEK
Courtesy GATE Collaboration
Courtesy R. Nartallo et al.,ESA
Widely used also in Space science and astrophysics Medical physics, nuclear medicine Radiation protection Accelerator physics Humanitarian projects, security etc.Technology transfer to industry, hospitals…
Born from the requirements of large scale HEP experiments
Most cited Most cited “Nuclear Science “Nuclear Science and Technology” and Technology”
publication!publication!
S. Agostinelli et al.GEANT4 - a simulation toolkit
NIM A 506 (2003) 250-303
Maria Grazia Pia, INFN Genova
LHC
ATLAS
LHCb
Complex physicsComplex physicsComplex detectorsComplex detectors
20 years software life-span
Maria Grazia Pia, INFN Genova
DosimetryDosimetry
Space scienceRadiotherapy Effects on components
Multi-disciplinary application environmentMulti-disciplinary application environment
Wide spectrum of physics coverage, variety of physics modelsPrecise, quantitatively validated physics
Accurate description of geometry and materials
Courtesy of ESACourtesy of CERN RADMON team
Maria Grazia Pia, INFN Genova
Dosimetry Dosimetry in Medicalin Medical ApplicationsApplications
Courtesy of L. Beaulieu et al., Laval
BrachytherapyRadiation Protection
Courtesy of J. Perl, SLAC
Hadrontherapy
Courtesy of P. Cirrone et al., INFN LNS
Courtesy of F. Foppiano et al,. IST and INFN Genova
Radiotherapy with external beams, IMRT
Courtesy of F. Foppiano et al., IST and INFN Genova
Maria Grazia Pia, INFN Genova
Exotic Geant4 applications…Exotic Geant4 applications…
FAO/IAEA International Conference on Area-Wide Control of Insect PestsArea-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
Precise dose calculationPrecise dose calculationGeant4 Low Energy Electromagnetic Physics Geant4 Low Energy Electromagnetic Physics
packagepackageElectrons and photons (250/100 eV < E < 100 GeV)
Models based on the Livermore libraries (EEDL, EPDL, EADL) Models à la Penelope
Hadrons and ions Free electron gas + Parameterisations (ICRU49, Ziegler) + Bethe-Bloch Nuclear stopping power, Barkas effect, chemical formula, effective charge etc.
Atomic relaxation Fluorescence, Auger electron emission, PIXE
Fe lines
GaAs lines
Atomic relaxationFluorescence
Auger effectshell effectsions
Maria Grazia Pia, INFN Genova
Fundamental concepts
Functionality: Functionality: physics, geometry etc.physics, geometry etc.Functionality: Functionality: physics, geometry etc.physics, geometry etc.
Software technologySoftware technologySoftware technologySoftware technology
Open source distributionOpen source distributionOpen source distributionOpen source distribution
Toolkit Toolkit Toolkit Toolkit
TransparencyTransparencyTransparencyTransparency
International CollaborationInternational CollaborationInternational CollaborationInternational Collaboration
Maria Grazia Pia, INFN Genova
PhysicsPhysicsFrom the Minutes of LCB (LHCC Computing Board) meeting on 21 October, 1997:
“It was noted that experiments have requirements for independent, alternative physics models. In Geant4 these models, differently from the concept of packages, allow the user to understandunderstand how the results are produced, and hence improve the physics validationphysics validation. Geant4 is developed with a modular architecture and is the ideal framework where existing components are integrated and new models continue to be developed.”
Maria Grazia Pia, INFN Genova
Domain decomposition
hierarchical structure of sub-
domains
Geant4 architecture
Uni-directional flow of
dependencies
Interface to external products w/o dependencies
Software EngineeringSoftware Engineeringplays a fundamental role in Geant4
User Requirements• formally collected• systematically updated• PSS-05 standard
Software Process• spiral iterative approach• regular assessments and improvements (SPI process)• monitored following the ISO 15504 model
Quality Assurance• commercial tools• code inspections• automatic checks of coding guidelines• testing procedures at unit and integration level• dedicated testing team
Object Oriented methods • OOAD• use of CASE tools
• openness to extension and evolution• contribute to the transparency of physics• interface to external software without dependencies
Use of Standards • de jure and de facto
Maria Grazia Pia, INFN Genova
ToolkitToolkitA set of compatible componentscomponents
each component is specialisedspecialised for a specific functionalityeach component can be refinedrefined independently to a great detailcomponents can be integratedintegrated at any degree of complexityit is easy to provide (and use) alternativealternative componentsthe user application can be customisedcustomised as needed
Openness to extensionextension and evolution evolution new implementations can be added w/o changing the existing code
Robustness and ease of maintenancemaintenance
protocolsprotocols and well defined dependenciesdependencies minimize coupling
OO OO technologytechnology
Strategic Strategic visionvision
Maria Grazia Pia, INFN Genova
http://www.ge.infn.it/geant4/dnahttp://www.ge.infn.it/geant4/dna
Maria Grazia Pia, INFN Genova
Biological models in Geant4 Biological models in Geant4
Relevance for space: Relevance for space: astronaut and aircrew radiation hazardsastronaut and aircrew radiation hazards
Project originally motivated and partly funded by
Maria Grazia Pia, INFN Genova
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 & open source release
DNADNA “Sister” activity to Geant4 Low-Energy Electromagnetic PhysicsGeant4 Low-Energy Electromagnetic PhysicsFollows the same rigorous software standards
INFN (Genova) - IN2P3 (CENBG)Partly sponsored by ESA
New collaborators welcome!
Maria Grazia Pia, INFN Genova
MultipleMultiple domains in the domains in the samesame software software environmentenvironment
Macroscopic levelMacroscopic level calculation of dose
already feasible with Geant4
develop useful associated tools
Cellular level cell modelling
processes for cell survival, damage etc.
DNA level DNA modelling
physics processes at the eV scale
bio-chemical processes
processes for DNA damage, repair etc.
Complexity of
software, physics and biologysoftware, physics and biology
addressed with an iterative and incremental software process
Parallel development at all the three levels
(domain decomposition)
Maria Grazia Pia, INFN Genova
What’s new?What’s new?Many “track structure” Monte Carlo codes previously developed A lot of modelling expertise embedded in these codes Each code implements oneone modelling approach (developed by its authors) “Stand-aloneStand-alone” codes, with limited application scope Legacy software technology (FORTRAN, procedural programming) Not publicly distributedNot publicly distributed
Geant4-DNAGeant4-DNA “Track structure” simulation in a general-purpose Monte Carlo system Toolkit approach: many interchangeable models Advanced software technology Rigorous software process software process Open sourceOpen source, freely available, supported by an international organization Foster a collaborative spirit in the scientific community Benefit of the feedback of a wider user community
Maria Grazia Pia, INFN Genova
11stst development cycle: development cycle:
Geant4 physics Geant4 physics extensionsextensions
Complex domain Physics: collaboration with theorists
Technology: innovative design technique introduced in Geant4
(1st time in Monte Carlo)
Experimental complexity as well Scarce experimental data
Collaboration with experimentalists for model validation
Geant4 physics validation at low energies is difficult!
Physics down to the eV scalePhysics down to the eV scale
Maria Grazia Pia, INFN Genova
Geant4-DNA physics Geant4-DNA physics processesprocesses
Models in liquid water More realistic than water vapour
Theoretically more challenging
Hardly any experimental data
New measurements needed
Status 1st -release Geant4 8.1
Full release on 14 December 2007
Further extensions in progress Models for water vapour
Models for other materials than water
Particle Processes
e-Elastic scatteringExcitationIonisation
pCharge decreaseExcitationIonisation
H Charge increaseIonisation
He++Charge decreaseExcitationIonisation
He+
Charge decreaseCharge increaseExcitationIonisation
HeCharge increaseExcitationIonisation
Specialised processes for low energy interactions with water
Maria Grazia Pia, INFN Genova
(Current) Physics Models(Current) Physics Models
e p H He+ HeElastic > 7.5 eV
Screened Rutherford + empirical
Brenner-Zaider
Excitation 7.5 eV – 10 keVA1B1, B1A1, Ryd A+B, Ryd C+D,
diffuse bands
10 eV – 500 keVDingfelder
500 keV – 10 MeVEmfietzoglou
100 eV – 10 MeVDingfelder Effective
charge scaling from same
models as for proton
Dingfelder
Charge Change
100 eV – 10 MeVDingfelder
100 eV – 10 MeVDingfelder
Ionisation7 eV – 10 keVEmfietzoglou
1b1, 3a1, 1b2, 2a1 + 1a1
100 eV – 500 keVRudd
500 keV – 10 MeVDingfelder (Born)
100 eV – 10 MeVDingfelder
Maria Grazia Pia, INFN Genova
Why these models?Why these models?No emotional attachment to any of the models Toolkit: offer a wide choice among many available alternatives
Complementary/alternative models
No “one size fits all”
Powerful design Abstract interfaces: the kernel is blind to any specific modelling
The system is intrinsically open to multiple implementations
Improvements, extensions, options Open system
Collaboration is welcome (experimental/modelling/software)
Maria Grazia Pia, INFN Genova
What is behind…What is behind…A policy defines a class or class template interface
Policy host classes are parameterised classes classes that use other classes as a parameter
Advantage w.r.t. a conventional strategy pattern Policies are not required to inherit from a base class
The code is bound at compilation time No need of virtual methods, resulting in faster execution
Policy-based Policy-based class designclass design
Policies can proliferate w/o any limitation
Syntax-oriented rather than signature-oriented
New technique
1st time introduced in Monte
Carlo
Weak dependency of the policy and the policy based class on the policy interface
Highly customizable designOpen to extension
Maria Grazia Pia, INFN Genova
Geant4-DNA physics processGeant4-DNA physics process
Deprived of any intrinsic physics functionality
Configured by
template specializationtemplate specialization to acquire physics properties
Handled transparently by Geant4 kernel
Maria Grazia Pia, INFN Genova
Development metricsDevelopment metricsOpen to extension: what does it mean in practice?
Implementation + unit test of a new physics model ~ 5 to 7 hours5 to 7 hours (average computing experience) No integration effort at all
Other software processes Peer review of the code Integration testing System testing Porting to other supported platforms User documentation Experimental validation
Investment in software technology!Investment in software technology!
Maria Grazia Pia, INFN Genova
More details on both software and physics in IEEE Trans. Nucl. Sci., IEEE Trans. Nucl. Sci., Vol. 54, no. 6, Dec. 2007Vol. 54, no. 6, Dec. 2007
Maria Grazia Pia, INFN Genova
Example of simulationExample of simulation
Liquid water sphere
0.2 µm diameter
1000 electrons shot from central source
E = 20 keV
Geant4 physics processes:
Elastic scattering
Excitation
Ionisation
0.2 µm
Shower of particles at
the nm / eV scale
Maria Grazia Pia, INFN Genova
How How accurate accurate are are Geant4-DNA physics Geant4-DNA physics models ?models ?
Both theoretical and experimental complexity in the very low energy régime
Theoretical calculations must take into account the detailed dielectric structure of the interacting material Approximations, assumptions, semi-empirical models
Experimental measurements are difficult Control of systematics
Practical constraints depending on the phase
Maria Grazia Pia, INFN Genova
Verification & ValidationVerification & Validation
Verification Conformity with theoretical models
Performed on all physics models
Validation Against experimental data
Lack of experimental data in liquid water in the very low energy range
New measurements needed
Evaluation of plausibility Only practical option at the present stage
Comparison against experimental data in water vapour/ice
Interesting also to study phase-related effects
Maria Grazia Pia, INFN Genova
A selection of resultsA selection of results
Systematic comparison in progress Survey of literature: extensive collection of experimental data
(goal: all!)
No time to show all of them ( paper)
Selection of a few interesting cases Highlight the complexity of the experimental domain
Discuss physics modelling features
S. Chauvie, S. Incerti, P. Moretto, M. G. Pia, Evaluation of Phase Effects in Geant4 Microdosimetry Models for Particle Interactions in Water, Proc. IEEE NSS 2007
Maria Grazia Pia, INFN Genova
Electron elastic scatteringElectron elastic scatteringTheoretical challenge to model accurately at very low energy
Various theoretical approaches at different degrees of complexity From simple screened Rutherford cross section to sophisticated phase shift
calculations
No experimental data in liquid water
Geant4-DNA Simple screened Rutherford cross section + semi-empirical model based on
vapour data
(Why so unsophisticated? Look at the experimental data…)
Open to evolution along with the availability of new data
Maria Grazia Pia, INFN Genova
Electron elastic scattering: Electron elastic scattering: total cross sectiontotal cross section
Evident discrepancy of the experimental data
Puzzle: inconsistency in recommended evaluated data from Itikawa & Mason, J. Phys. Chem. Ref. Data, 34-1, pp. 1-22, 2005.
Geant4-DNA Better agreement with some of
the data sets
Hardly conclusive comparison, given the experimental status…
Geant4-DNA elastic Itikawa & Mason elastic (recommended) Itikawa & Mason total (recommended) Danjo & NishimuraSeng et al. Sueoka et al. Saglam et al.
Recommended total cross section smaller than elastic only one!
Not all available experimental data reported… the picture would be too crowded!
Maria Grazia Pia, INFN Genova
Electron ionisationElectron ionisation
Semi-empirical model D. Emfietzoglou and M. Moscovitch, “Inelastic collision
characteristics of electrons in liquid water”, NIM B, vol. 193, pp. 71-78, 2002
Based on dielectric formalism for the valence shells (1b1, 3a1, 1b2 and 2a1) responsible for condensed-phase effects
Based on the binary encounter approximation for the K-shell (1a1)
Maria Grazia Pia, INFN Genova
Electron ionisation:Electron ionisation:total cross sectiontotal cross section
Different phases Geant4-DNA model:
liquid water Experimental data:
vapour
Plausible behaviour of Geant4 implementation
Phase differences appear more significant at lower energies
Geant4-DNA Born ionisation Itikawa & Mason ionisation (recommended)
Maria Grazia Pia, INFN Genova
Proton ionisationProton ionisation
Cross section based on two complementary models
a semi-empirical analytical approach with parameters specifically calculated for liquid water
for 100 eV < E < 500 keV
a model based on the Born theory
for 500 keV < E < 10 MeV
• M. Dingfelder et al., “Inelastic-collision cross sections of liquid water for interactions of energetic protons”, Radiat. Phys. Chem., vol. 59, pp. 255-275, 2000. • M. E. Rudd et al., “Cross sections for ionisation of water vapor by 7-4000 keV protons”, Phys. Rev. A, vol. 31, pp. 492-494, 1985.• M. E. Rudd et al., “Electron production in proton collisions: total cross sections”, Rev. Mod. Phys., vol. 57, no. 4, pp. 965-994, 1985.
Maria Grazia Pia, INFN Genova
Proton ionisation: Proton ionisation:
total cross sectiontotal cross sectionAll measurements performed by the same team
at different accelerators and time
Even data taken by the same group exhibit inconsistencies !
systematic is difficult to control in delicate experimental conditions
Geant4-DNA models look plausible
Hard to discuss phase effects in these experimental conditions!
Goodness-of-fit test Geant4 DNA model incompatible with
experimental data (p-value < 0.001)
Compatibility w.r.t. data fit? Cramer-von Mises test: p-value = 0.1 Anderson-Darling test: p-value <0.001
PNL data early Van de Graaff data late Van de Graaff data early Univ. Nebraska-Lincoln data late Univ. Nebraska-Lincoln data tandem Van de Graaff data
Geant4-DNA
Fit to experimental
data
M. E. Rudd, T. V. Goffe, R. D. DuBois, L. H. Toburen, “Cross sections for ionisation of water vapor by 7-4000 keV protons”, Phys. Rev. A, vol. 31, pp. 492-494, 1985.
Different phasesGeant4-DNA model: liquid waterExperimental data: vapour
Maria Grazia Pia, INFN Genova
Proton and hydrogen charge change Proton and hydrogen charge change
Cross section based on a semi-empirical approach Described by an analytical formula
With parameters optimised from experimental data in vapour
• M. Dingfelder et al., “Inelastic-collision cross sections of liquid water for interactions of energetic protons”, Radiat. Phys. Chem., vol. 59, pp. 255-275, 2000.• B. G. Lindsay et al., “Charge transfer of 0.5-, 1.5-, and 5-keV protons with H2O: absolute differential and integral cross sections”, Phys. Rev. A, vol. 55, no. 5, pp. 3945-3946, 1997.• R. Dagnac et al., “A study on the collision of hydrogen ions H+
1 , H+2 and H+
3 with a water-vapour target”, J. Phys. B, vol. 3, pp. 1239-1251, 1970.• L. H. Toburen et al., “Measurement of highenergy charge transfer cross sections for incident protons and atomic hydrogen in various gases”, Phys. Rev., vol. 171, no. 1, pp. 114-122, 1968
Maria Grazia Pia, INFN Genova
Charge change cross section: Charge change cross section: proton and hydrogenproton and hydrogen
Different phases Geant4-DNA model: liquid Experimental data: vapour
Goodness-of-fit test Geant4-DNA model experimental data (white symbols only)
Anderson-Darling test Cramer-von Mises test Kolmogorov-Smirnov test Kuiper test Watson test
p-value > 0.1 from all tests
… … but some data were used to but some data were used to optimise the semi-empirical optimise the semi-empirical
model!model!
Lindsay et al. Dagnac et al. Toburen et al. Berkner et al. Cable Koopman Chambers et al.
Large discrepancies
among the data!
Maria Grazia Pia, INFN Genova
Conclusion from Conclusion from comparisonscomparisonsGeant4-DNA models (liquid) look plausible when compared to available experimental data (vapour)
More experimental data are neededMore experimental data are needed In liquid water for simulation model validation
In vapour and ice to study the importance of phase effects in modelling particle interactions with the medium
With good control of systematiccontrol of systematic and reproducibilityreproducibility of experimental conditions!
Hard to draw firm conclusions about phase effects Available experimental data exhibit significant discrepancies in many cases
Some of these data have been already used to constrain or optimize semi-empirical models
Maria Grazia Pia, INFN Genova
Exploiting the toolkitExploiting the toolkitFor the first time
a general-purpose Monte Carlogeneral-purpose Monte Carlo system is equipped with functionality specific
to the simulation of biological effects of radiationbiological effects of radiation
Geant4-DNA physics processes User InterfaceKernel
Geometry Visualisation
Maria Grazia Pia, INFN Genova
Microdosimetry in high resolution cellular phantoms
with Geant4-DNA
© IPB/CENBG
Maria Grazia Pia, INFN Genova
ContextContextUnderstanding the health effects of low doses of ionizing radiation is the challenge of today’s radiobiology research
At the cell scale, recent results include the observation of bystander effects adaptive response gene expression changes genomic instability genetic susceptibility
► May question the validity of health risk estimation at low doses of radiation
► Consequences for radiotherapy, environment exposure, space exploration…
Dedicated worldwide experimental facilities to investigate the interaction of ionizing radiation with living cells radioactive sources classical beams microbeams: allow a perfect control of the deposited dose in the targeted cell
(e.g. the CENBG irradiation facility in France)
Maria Grazia Pia, INFN Genova
AIFIRA equipped with a cellular irradiation microbeam line
3 MeV proton or beam
single cell & single ion mode
Targeting accuracy on living cells in air: a few µm
Able to quantify DNA damages like double strand breaks
CENBG AIFIRA irradiation facility
in Bordeaux, France
© IPB/CENBG
Maria Grazia Pia, INFN Genova
Realistic cellular geometries Realistic cellular geometries from confocal microscopyfrom confocal microscopy
ability to control depth of fielddepth of field
elimination of background informationbackground information away from the focal plane
(that leads to image degradation)
collect serial optical sectionsoptical sections from thick specimens
© Olympus
Confocal microscopy offers several advantages over
conventional widefield optical microscopy
Maria Grazia Pia, INFN Genova
Confocal microscopyConfocal microscopyImages of human keratinocyte cells HaCaT/(GFP-H2B)Tg acquired at CENBG cell line used in single cell irradiation at CENBG
Cells fixed after 4 hours or 24 hours of incubation (cell irradiation conditions)
Staining Nucleus: Hoechst 33342 dye (DNA marker)
Cytoplasm: propidium iodide, (RNA and DNA marker).
Nucleoli (high chromatine and protein concentration regions): idem
Acquisition 2D images acquired every 163 nm with a Leica® DMR TCS SP2
confocal microscope
several 2D resolutions, up to 512 × 512 pixels
Image reconstruction 3D stacking using the Leica Confocal Software®
filtering and phantom geometry reconstruction with Mercury® Computer Systems, Inc. Amira® suite
© IPB/CENBG
© IPB/CENBG
Maria Grazia Pia, INFN Genova
Building cellular modelsBuilding cellular models
Selection of four “phantoms” reconstructed from 128×128 2D confocal images.
Incubation : 4 hours for cells a and b
24 hours for cells c and d
The cytoplasm and nucleoli appear in red while the nucleus is shown in blue
© IPB/CENBG
a b
c d
Maria Grazia Pia, INFN Genova
Geometry modellingGeometry modelling
Not available in ad-hoc
Monte Carlo codes
Exploit the advantage of a general purpose Monte Carlo system
Powerful Geant4 geometry packagePowerful Geant4 geometry package
Use of functionality already existing in Geant4
Voxel geometriesVoxel geometries +
Navigation optimisation techniquesNavigation optimisation techniques
Direct benefit from investment in the Geant4 toolkit
Realistic rendering of the biological systemsImportant for overall realistic simulation
results
Parameterised volumesNested parameterisation
Maria Grazia Pia, INFN Genova
Cellular phantoms in Cellular phantoms in Geant4Geant4
Implemented either as parameterised volumes or nested geometries
(faster navigation above 64x64 resolution)
Composition: liquid water (compatible with Geant4 DNA models)
These cellular models are publicly available in the Geant4 microbeammicrobeam Advanced Example geant4/examples/advanced/microbeam
011
1 2 3
011
1 2 31 2 3
4 5 …
1 2 3
4 5 …
Maria Grazia Pia, INFN Genova
2.37 MeV +
hitting the cell
Cellular phantom modelCellular phantom model
24h incubated cell
Irradiated with a 2.37 MeV + beam
64 x 64 x 60 resolution
0.36 x 0.36 x 0.16 µm3 voxel size
cytoplasm
nucleus~10 µm
Maria Grazia Pia, INFN Genova
Shower in cellular Shower in cellular phantomphantom
Ch
arg
e d
ecre
ase
Ch
arg
e in
cre
ase
Ela
sti
c s
catt
eri
ng
Excit
ati
on
Ion
isati
on
(unit: µm)
2.37 MeV + delivered on targeted cell by the CENBG microbeam irradiation facility
• G4 DNA processes• CPU ~45 min(preliminary timing)
ZOOM
Maria Grazia Pia, INFN Genova
Geant4 DNA capabilitiesGeant4 DNA capabilities
With this Geant4 extension, it is now possible to study the energy deposit distribution produced by a primary particle and its secondaries inside a cell
Access distributions in nucleus, cytoplasm, mitochondria…
What you get in return is more than your own investment!
Maria Grazia Pia, INFN Genova
Changing scaleChanging scaleLarge effort for microscopic modelling of interactions and biological systems in Geant4
Parallel approach: macroscopic modelling in Geant4
Concept of dose in a cell population
Statistical evaluation of radiation effects from empirical data
All this is possible in the same simulation environment (toolkit)
Human cell lines irradiated with X-rays
Courtesy E. Hall
Example: modelling cell survival fractioncell survival fraction
in a population of irradiated cells
Maria Grazia Pia, INFN Genova
ExampleExample Computation of dose in a cell population and estimation of survival fraction
Monolayer
V79-379A cells
Proton beam
E= 3.66 MeV/n
Linear-Quadratic model
Folkard et al., Int. J. Rad. Biol., 1996
α = 0.32β = -0.039
Macroscopic cell survival models to be distributed in Geant4 (advanced example in preparation)
Dose (Gy)
Continuous line:LQ theoretical model
with Folkard parameters
Data points:Geant4 simulation results
Su
rviv
al
Maria Grazia Pia, INFN Genova
ConclusionConclusionThe Geant4 DNA processes are publicly available
Can be applied to realistic cell geometries
Full comparison against vapour/ice will be published evaluation of phase effects
Thanks to the flexibility of policy-based code design of Geant4 DNA, any interaction model can be easily implemented in a few hours and automatically integrated in Geant4 !
Not limited to radiation biology…
Maria Grazia Pia, INFN Genova
PerspectivesPerspectivesShort term Geant4 DNA processes
will be publicly available in Geant4 9.1 on 14 December 2007
Microdosimetry advanced example will be available in the next Geant4 releases (presumably end of June 2008) illustrates how to use the Geant4 DNA physics processes
Cellular survival advanced example in preparation
Other physics models thanks to the novel software design
Longer term Chemical phase: production of radical species
Geometry-dedicated development cycle: DNA geometry modelling
Biological phase: prediction of DNA damages (double strand breaks – fatal lesions, DNA fragments…) after irrradiation
Other materials than liquid water: DNA bases, silicon etc.
Maria Grazia Pia, INFN Genova
For discussion…For discussion…
Geant4-DNA proposes a paradigm shift Open source, freely available software
Microdosimetry/radiobiology functionality in a general-purpose Monte Carlo code
Availability of multiple models in the same environment
Equal importance to functionality and software technology
Foster collaboration within the scientific community Theoretical modelling, experimental measurements, software technology
Promote feedback from users of the software
Comments and suggestions are welcome...
Maria Grazia Pia, INFN Genova
AcknowledgmentAcknowledgmentThanks to M. Dingfelder and D. Emfietzoglou for theoretical support
W. Friedland and H. Paretzke for fruitful discussions and suggestions
P. Nieminen for motivation and support to the project through ESA funding
COST-P9 for supporting short-term visits
R. Capra, Z. Francis, G. Montarou for preliminary contributions at an early stage
G. Cosmo and I. McLaren for support in the Geant4 system testing process
K. Amako for support in releasing the Geant4-DNA code documentation
Z. W. Bell (TNS Senior Editor) for his advice in the paper publication process
CERN Library for providing many reference papers
Thanks to Nigel Mason and CECAM for organizing this workshop and supporting our participation!