Post on 26-Mar-2015
Maria Grazia Pia, INFN Genova
Geant4 for MicrodosimetryGeant4 for Microdosimetry
MMD 2005Wollongong, 5-8 November 2005
DNADNA
R. Capra, S. Chauvie, Z. Francis, S. Guatelli, S. Incerti, B. Mascialino, Ph. Moretto, G. Montarou, P. Nieminen, Maria Grazia Pia
Maria Grazia Pia, INFN Genova
Object Oriented Toolkit for Object Oriented Toolkit for the simulation of particle the simulation of particle interactions with matterinteractions with matter
An experiment of distributed software production distributed software production
and managementand management
An experiment of application of rigorous software engineering methodologiessoftware engineering methodologies
and object oriented technology object oriented technology to the particle physics environment
also…
Born from the requirements of large scale HEP experiments
Widely used not only in HEP
• Space science and astrophysics• Medical physics, medical imaging• Radiation protection• Accelerator physics• Pest control, food irradiation• Landmining, security• etc.
• Technology transfer
R&D phase: RD44, 1994 - 1998
1st release: December 1998
2 new releases/year since then
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
in a in a nutshellnutshell
Rigorous software engineering– Iterative-incremental software process– Object oriented methods– Quality assurance
Geometry– Powerful and versatile geometry modelling– Multiple solid representations handled through
the same abstract interface (CSG, STEP compliant solids, BREPs)
– Simple placements, parameterised volumes, replicas, assembly-volumes etc.
– Boolean operations on solids
Physics independent from tracking
Subject to rigorous, quantitative validation
Electromagnetic physics– Standard, Low-Energy, Muon, Optical etc.
Hadronic physics– Parameterised, data-driven, theory-driven
models
Interactive capabilities– Visualisation, UI/GUI– Multiple drivers to external systems
Maria Grazia Pia, INFN Genova
Geant4 CollaborationGeant4 Collaboration
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.
MoU basedDevelopment, Distribution and User Support of Geant4
~100 members
Maria Grazia Pia, INFN Genova
Dosimetry with Geant4Dosimetry with Geant4
Radfet #2 Radfet #4
Radfet #1#3
S300/50G300/50D300/50D690/15
DG300/50
G690/15
S690/15
DG690/15
Bulk
BulkDiode
Space science
Radiotherapy Effects on components
Multi-disciplinary application environment
Wide spectrum of physics coverage, variety of physics modelsPrecise, quantitatively validated physics
Accurate description of geometry and materials
Maria Grazia Pia, INFN Genova
Dosimetry Dosimetry in Medicalin Medical ApplicationsApplications
Courtesy of L. Beaulieu et al., Laval
Radiotherapy with external beams, IMRT
Brachytherapy
Hadrontherapy
Radiation Protection
Courtesy of J. Perl, SLAC
Courtesy of P. Cirrone et al., INFN LNS
Courtesy of S. Guatelli et al,. INFN Genova
Courtesy of F. Foppiano et al., IST Genova
Maria Grazia Pia, INFN Genova
Precise dose calculationPrecise dose calculationGeant4 Low Energy Electromagnetic Physics packageElectrons 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
Fe lines
GaAs lines
Atomic relaxationFluorescence
Auger effectshell effectsions
Maria Grazia Pia, INFN Genova
A medical accelerator for IMRTA medical accelerator for IMRT
Kolmogorov-Smirnov test
p-value = 1
depth dose profile
Simulation Exp. data
range D p-value
-84 -60 mm 0.385 0.23
-59 -48 mm 0.27 0.90
-47 47 mm 0.43 0.19
48 59 mm 0.30 0.82
60 84 mm 0.40 0.10
lateral dose profileSimulation Exp. data tumour
healthy tissue
Maria Grazia Pia, INFN Genova
MicroSelectron-HDR source
Endocavitary brachytherapy
Superficial brachytherapy
Interstitial brachytherapy
Bebig Isoseed I-125 source
Maria Grazia Pia, INFN Genova
Dosimetry: protons and Dosimetry: protons and ionsionsagreement with data
better than 3%Further validation tests in progress
WHOLE PEAK
(N1=149 N2=66)
Cramer –
von Mises test
Anderson – Darling test
Test statistics 0.06 0.499375
p-value 0.79 0.747452
0.52 0.443831Electromagnetic only
Inventory of Geant4 hadronic models
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
Radiation protection for Radiation protection for interplanetary manned interplanetary manned missionsmissions
Maria Grazia Pia, INFN Genova
2.15 cm Al
10 cm water
5 cm water
4 cm Al
rigid/inflatablerigid/inflatablehabitats are equivalenthabitats are equivalent
10 cm water5 cm water
Doubling the shielding Doubling the shielding thickness decreases the thickness decreases the energy deposit by ~10% energy deposit by ~10%
10 cm water10 cm polyethylene
e.m. physics + Bertini set
e.m. physics
only
shielding shielding materialsmaterials
S. Guatelli et al., Geant4 Simulation for interplanetary manned missions, to be submitted December 2005
Maria Grazia Pia, INFN Genova
AnthropomorphiAnthropomorphic Phantomsc Phantoms
A major concern in radiation protection is the
dose accumulated in organs at riskdose accumulated in organs at risk
Development of anthropomorphic phantom models for Geant4
– evaluate dose deposited in critical organs
Original approachOriginal approach
– analytical and voxel phantomsanalytical and voxel phantoms in the same simulation environment
Analytical phantomsAnalytical phantomsGeant4 CSG, BREPS solids
Voxel phantomsVoxel phantomsGeant4 parameterised volumes
GDMLGDML for geometry description storage
Maria Grazia Pia, INFN Genova
Radiation exposure Radiation exposure of astronautsof astronauts
5 cm water shielding
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10 cm water shielding
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Dose calculation in critical organs
Effects of external shieldingexternal shielding self-body shieldingself-body shielding
Preliminary
Maria Grazia Pia, INFN Genova
Object Oriented technology+
Geant4 architecture
Processes are handled transparently by Geant4 kernel
through an
abstract interfaceabstract interface
Geometry objects (solids, logical volumes, physical volumes)
are handled transparently by Geant4 kernel through
abstract interfacesabstract interfaces
So why not describing DNA?
So what about mutagenesis as a
process?
DNADNA
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
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
ToolkitToolkitA set of compatible components
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 dependencies dependencies minimize coupling
OO OO technologytechnology
Strategic Strategic visionvision
Maria Grazia Pia, INFN Genova
“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 & open source release
The concept of “dose” fails at cellular The concept of “dose” fails at cellular and DNA scalesand DNA scales
It is desirable to gain an understanding to the processes at all levels
(macroscopic vs. microscopic)DNADNA
Maria Grazia Pia, INFN Genova
Multiple domains in the Multiple domains in the same software same software environmentenvironment
Macroscopic 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
http://www.ge.infn.it/geant4/dnahttp://www.ge.infn.it/geant4/dna
Maria Grazia Pia, INFN Genova
Cou
rtes
y A
. Bra
hme
(KI)
Courtesy A. Brahme (Karolinska Institute)
Biological processesBiological processes
PhysicalPhysicalprocessesprocesses
BiologicalBiologicalprocessesprocesses
ChemicalChemicalprocessesprocesses
Known, available
Unknown, not available
E.g. E.g. generation of generation of free radicals free radicals in the cellin the cell
Maria Grazia Pia, INFN Genova
RequirementsProblem domain analysis
Theories and models for cell survivalTheories and models for cell survival
TARGET THEORY MODELSTARGET THEORY MODELS Single-hit model Multi-target single-hit model Single-target multi-hit model
MOLECULAR THEORY MODELSMOLECULAR THEORY MODELS Theory of radiation action Theory of dual radiation action Repair-Misrepair model Lethal-Potentially lethal model
Analysis & DesignImplementationTest
Experimental validation of Geant4 simulation models
Critical evaluation of the models
in progress
Cellular level Cellular level Cellular level Cellular level
Geant4 approach: variety of models all handled through the same abstract interface
Maria Grazia Pia, INFN Genova
Target theory modelsTarget theory models
Single-hitmodel
Multi-targetsingle-hit
model
Single-targetmulti-hitmodel
Joiner & Johns model
No hits: cell survivesOne or more hits: cell dies
S(ρ,Δ) = PSURV (ρ0, h=0, Δ) = (1- ρ0)Δ = exp[Δ ln (1- ρ0)]
PSURV(q,b,n,D) = B(b) (e-qD)(n-b) (1- e-qD)b n!
b! (n -b)!
Extension of single-hit model
S = e-αR [1 + ( αS / αR -1) e ] D – ß D - D/DC
Cell survival equationsCell survival equations based on
model-dependent assumptions
S= e-ßD 2
two hits
No assumption on: • TimeTime• Enzymatic repair of DNAEnzymatic repair of DNA
Maria Grazia Pia, INFN Genova
Molecular theory of radiation action
(linear-quadratic model)
Theory of dualradiation action
Repair or misrepair of cell survival
Lethal-potentiallylethal model
Chadwick and Leenhouts (1981)
Tobias et al. (1980)
Kellerer and Rossi (1971)
Curtis (1986)
Molecular models for cell Molecular models for cell deathdeath
More sophisticated modelsMore sophisticated models
Maria Grazia Pia, INFN Genova
TARGET
THEORY
SINGLE-HIT
TARGET
THEORY
MULTI-TARGET
SINGLE-HIT
MOLECULAR
THEORY
RADIATION ACTION
MOLECULAR
THEORY
DUAL RADIATION ACTION
MOLECULAR
THEORY
REPAIR-MISREPAIR
LIN REP / QUADMIS
MOLECULAR
THEORY
REPAIR-MISREPAIR
LIN REP / MIS
MOLECULAR
THEORY
LETHAL-POTENTIALLY LETHAL
MOLECULAR
THEORY
LETHAL-POTENTIALLY LETHAL – LOW DOSE
MOLECULAR
THEORY
LETHAL-POTENTIALLY LETHAL – HIGH DOSE
MOLECULAR
THEORY
LETHAL-POTENTIALLY LETHAL – LQ APPROX
S= e-D / D0
S = 1- (1- e-qD)n
S = e –p ( αD + ßD )2
S = S0 e - k (ξ D + D ) 2
S = e-αD[1 + (αD / ε)]εΦ
S = e-αD[1 + (αDT / ε)]ε
S = exp[ - NTOT[1 + ]ε ] ε (1 – e- εBAtr)NPL
S = e-ηAC D
- ln[ S(t)] = (ηAC + ηAB) D – ε ln[1 + (ηABD/ε)(1 – e-εBA tr)]
- ln[ S(t)] = (ηAC + ηAB e-εBAtr ) D + (η2AB/2ε)(1 – e-εBA tr)2 D2]
S = e-q1D [ 1- (1- e-qn D)n ]
REVISED MODEL
In progress: evaluation of
model parameters from clinical
data
Maria Grazia Pia, INFN Genova
Low Energy Physics extensionsLow 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
Processes for other material than water to follow– interest for radiation effects on components
DNA levelDNA levelDNA levelDNA level
Electrons Protons (H+) Hydrogen (H) Alpha (He++) He+ He
ElasticBrenner (7.5 - 200 eV)
Negligible effect Negligible effect Negligible effect Negligible effect Negligible effectEmfietzoglou (> 200 ev)
ExcitationEmfietzoglou Miller and Green
Negligible effectMiller and Green Miller and Green Miller and Green
Born (7 ev – 10 keV) Born (100 eV – 10 MeV) (1 keV – 15 MeV) (1 keV – 15 MeV) (1 keV – 15 MeV)
Charge decreaseDingfelder
In progress In progress(100 eV – 2 MeV)
Charge increaseMiller and Green
In progress In progressDingfelder (0.1 Kev – 100 MeV)
Ionization In progressRudd (0.1 - 500 keV)
Rudd (0.1 – 100 MeV) In progress In progress In progressIn progress (> 500 keV)
Not pertinent to this particle
Not pertinent to this particle
Not pertinent to this particle
Not pertinent to this particle
Not pertinent to this particle
Not pertinent to this particle
Current statusCurrent status
Maria Grazia Pia, INFN Genova
Development processDevelopment process
Complex domain– physics– software
Collaboration with theorists
Innovative design introduced in Geant4– Policy-based class design– Parameterised classes: policies are cross section models, models for final
state calculation etc.– Flexibility of modelling + performance optimisation
Collaboration with experimentalists for model validation would be helpful
– Geant4 physics validation at low energies is difficult!
Maria Grazia Pia, INFN Genova
Electrons Protons (H+) Hydrogen (H) Alpha (He++) He+ He
ElasticBrenner (7.5 - 200 eV)
Negligible effect Negligible effect Negligible effect Negligible effect Negligible effectEmfietzoglou (> 200 ev)
ExcitationEmfietzoglou Miller and Green
Negligible effectMiller and Green Miller and Green Miller and Green
Born (7 ev – 10 keV) Born (100 eV – 10 MeV) (1 keV – 15 MeV) (1 keV – 15 MeV) (1 keV – 15 MeV)
Charge decreaseDingfelder
In progress In progress(100 eV – 2 MeV)
Charge increaseMiller and Green
In progress In progressDingfelder (0.1 Kev – 100 MeV)
Ionization In progressRudd (0.1 - 500 keV)
Rudd (0.1 – 100 MeV) In progress In progress In progressIn progress (> 500 keV)
Process not pertinent to this particle
Process not pertinent to this particle
Process not pertinent to this particle
Process not pertinent to this particle
Process not pertinent to this particle
Process not pertinent to this particle
Electrons Protons (H+) Hydrogen (H) Alpha (He++) He+ He
ElasticBrenner (7.5 - 200 eV)
Negligible effect Negligible effect Negligible effect Negligible effect Negligible effectEmfietzoglou (> 200 ev)
ExcitationEmfietzoglou Miller and Green
Negligible effectMiller and Green Miller and Green Miller and Green
Born (7 ev – 10 keV) Born (100 eV – 10 MeV) (1 keV – 15 MeV) (1 keV – 15 MeV) (1 keV – 15 MeV)
Charge decreaseDingfelder
In progress In progress(100 eV – 2 MeV)
Charge increaseMiller and Green
In progress In progressDingfelder (0.1 Kev – 100 MeV)
Ionization In progressRudd (0.1 - 500 keV)
Rudd (0.1 – 100 MeV) In progress In progress In progressIn progress (> 500 keV)
Process not pertinent to this particle
Process not pertinent to this particle
Process not pertinent to this particle
Process not pertinent to this particle
Process not pertinent to this particle
Process not pertinent to this particle
Electrons Protons (H+) Hydrogen (H) Alpha (He++) He+ He
ElasticBrenner (7.5 - 200 eV)
Negligible effect Negligible effect Negligible effect Negligible effect Negligible effectEmfietzoglou (> 200 ev)
ExcitationEmfietzoglou Miller and Green
Negligible effectMiller and Green Miller and Green Miller and Green
Born (7 ev – 10 keV) Born (100 eV – 10 MeV) (1 keV – 15 MeV) (1 keV – 15 MeV) (1 keV – 15 MeV)
Charge decreaseDingfelder
In progress In progress(100 eV – 2 MeV)
Charge increaseMiller and Green
In progress In progressDingfelder (0.1 Kev – 100 MeV)
Ionization In progressRudd (0.1 - 500 keV)
Rudd (0.1 – 100 MeV) In progress In progress In progressIn progress (> 500 keV)
Process not pertinent to this particle
Process not pertinent to this particle
Process not pertinent to this particle
Process not pertinent to this particle
Process not pertinent to this particle
Process not pertinent to this particle
Cross sections
Final state generation
Process kinematics
Maria Grazia Pia, INFN Genova
Elastic scatteringElastic scatteringTotal cross section
Angular distribution
Phys. Med. Biol. 45 (2000) 3171-3194Solid line: our model
● Brenner● Emfietzoglou
10 eV100 eV
200 eV500 eV
1 keV
J. Phys. D 33 (2000) 932-944
Preliminary
Maria Grazia Pia, INFN Genova
Excitation Excitation
Testing still in progress
(m2)
E(eV)
p + H20 p + H
20*
Rad. Phys. Chem. 59 (2000) 255-275
m2)
E(eV)
e- + H20 e- + H
20*
Preliminary
Maria Grazia Pia, INFN Genova
ExcitationExcitation
E(eV)
He + H2O He + H
2O*
He+ + H2O He+ + H
2O*
He++ + H2O He++ + H
2O*
(m2)
(m2)
E(eV)
Rad. Phys. Chem. 59 (2000) 255-275
Preliminary
Maria Grazia Pia, INFN Genova
Charge transferCharge transfer
Charge transfer by protons/Hydrogen is implemented
Charge transfer by Helium is still to be implemented
E(eV)
(m2)
Helium
p + H20 H + H
20+ + E
H + H20 p + e- + H
20
Preliminary
Maria Grazia Pia, INFN Genova
IonisationIonisation
Proton (< 500 keV) and Hydrogen ionisation implemented Development of remaining ionisation processes still ongoing
ln(E/eV)
(m2)
H + H20 H + e- + H
20+
p + H20 p + e- + H
20+
Preliminary
Maria Grazia Pia, INFN Genova
Scenario Scenario for Mars (and earth…)for Mars (and earth…)
Geant4 simulationspace environment
+spacecraft, shielding etc.
+anthropomorphic phantom
Dose in organs at risk
Geant4 simulation with biological
processes at cellular level (cell survival,
cell damage…)
Phase space input to nano-simulation
Geant4 simulation with physics at eV scale
+DNA processes
Oncological risk to Oncological risk to astronauts/patientsastronauts/patients
Risk of nervous Risk of nervous system damagesystem damage
Geant4 simulationtreatment source
+geometry from CT image
oranthropomorphic phantom
Maria Grazia Pia, INFN Genova
ConclusionsConclusionsGeant4 offers powerful geometry and physics modelling in an advanced computing environmentWide spectrum of complementary and alternative physics models
Multi-disciplinary applications of dosimetry simulationPrecision 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