1. Geant4 for Microdosimetry
DNA
Geant4 for Microdosimetry
R. Capra, S. Chauvie, Z. Francis, S. Guatelli, S. Incerti, B. Mascialino,
Ph. Moretto, G. Montarou, P. Nieminen, Maria Grazia Pia
MMD 2005
Wollongong, 5-8 November 2005

2. Born from the requirements of large scale HEP experiments
Object Oriented Toolkit for the simulation of particle interactions with matter
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
also…
An experiment of
distributed software production
and management
An experiment of application of rigorous software engineering methodologies
and object oriented technology
to the particle physics environment
R&D phase: RD44,
1st release: December 1998
2 new releases/year since then

3. in a nutshell Domain decomposition
hierarchical structure of sub-domains
Geant4 architecture
Uni-directional flow of dependencies
Interface to external products w/o dependencies
in a nutshell
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

4. Geant4 Collaboration ~100 members MoU based
Development, Distribution and User Support of Geant4
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.

5. Dosimetry with Geant4
Wide spectrum of physics coverage, variety of physics models
Precise, quantitatively validated physics
Accurate description of geometry and materials
Multi-disciplinary application environment
Radfet #2
Radfet #4
Radfet #1#3
S300/50
G300/50
D300/50
D690/15
DG300/50
G690/15
S690/15
DG690/15
Bulk
Diode
Space science
Radiotherapy
Effects on components

6. Dosimetry in Medical Applications
Courtesy of F. Foppiano et al., IST Genova
Radiotherapy with external beams, IMRT
Courtesy of P. Cirrone et al., INFN LNS
Hadrontherapy
Courtesy of S. Guatelli et al,. INFN Genova
Brachytherapy
Radiation Protection
Courtesy of J. Perl, SLAC
Courtesy of L. Beaulieu et al., Laval

7. Precise dose calculation
Geant4 Low Energy Electromagnetic Physics package
Electrons 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 relaxation
Fluorescence Auger effect
shell effects
ions

8. A medical accelerator for IMRT
p-value = 1
depth dose profile
Simulation Exp. data
lateral dose profile
Simulation Exp. data
tumour
healthy tissue
Kolmogorov-Smirnov test
Rigorous software engineering is important in the medical physics domain
to be maintainable over a large time scale
to be extensible, to accommodate new user requirements (thanks to the OO technology)
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

9. MicroSelectron-HDR source
Endocavitary brachytherapy
Interstitial brachytherapy
MicroSelectron-HDR source
Superficial brachytherapy
Bebig Isoseed I-125 source

10. Dosimetry: protons and ions
agreement 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
p-value
0.79
Electromagnetic only
0.52
Inventory of Geant4 hadronic models

11. 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

12. Radiation protection for interplanetary manned missions

13. habitats are equivalent
Doubling the shielding thickness decreases the energy deposit by ~10%
10 cm water
5 cm water
S. Guatelli et al., Geant4 Simulation for interplanetary manned missions,
to be submitted December 2005
2.15 cm Al
10 cm water
5 cm water
4 cm Al
rigid/inflatable
habitats are equivalent
10 cm water
10 cm polyethylene
e.m. physics + Bertini set
e.m. physics only
shielding materials

14. Anthropomorphic Phantoms
A major concern in radiation protection is the dose accumulated in organs at risk
Development of anthropomorphic phantom models for Geant4
evaluate dose deposited in critical organs
Original approach
analytical and voxel phantoms in the same simulation environment
Anthropomorphic Phantoms
Analytical phantoms
Geant4 CSG, BREPS solids
Voxel phantoms
Geant4 parameterised volumes
GDML
for geometry description storage

15. Radiation exposure of astronauts
5 cm water shielding
Skull
Upper spine
Lower spine
Arm bones
Leg bones
Womb
Stomach
Upper intestine
Lower intestine
Liver
Pancreas
Spleen
Kidneys
Bladder
Breast
Overies
Uterus
Preliminary
10 cm water shielding
Skull
Upper spine
Lower spine
Arm bones
Leg bones
Womb
Stomach
Upper intestine
Lower intestine
Liver
Pancreas
Spleen
Kidneys
Bladder
Breast
Overies
Uterus
Dose calculation in critical organs
Effects of external shielding
self-body shielding

16. DNA Object Oriented technology + Geant4 architecture
Geometry objects
(solids, logical volumes, physical volumes)
are handled transparently by Geant4 kernel through
abstract interfaces
So why not describing DNA?
Processes are handled transparently by Geant4 kernel through an
abstract interface
So what about mutagenesis as a process?
Object Oriented technology +
Geant4 architecture

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

18. Physics
From 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 understand how the results are produced, and hence improve the physics 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.”

19. Strategic vision OO technology Toolkit
Openness to extension and evolution
new implementations can be added w/o changing the existing code
Robustness and ease of maintenance
protocols and well defined dependencies minimize coupling
Strategic vision
Toolkit
A set of compatible components
each component is specialised for a specific functionality
each component can be refined independently to a great detail
components can be integrated at any degree of complexity
it is easy to provide (and use) alternative components
the user application can be customised as needed

20. The concept of “dose” fails at cellular and DNA scales
It is desirable to gain an understanding to the processes at all levels (macroscopic vs. microscopic)
“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:
Collection of user requirements & first prototypes
Second phase: started in 2004
Software development & open source release

21. Multiple domains in the same software environment
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 biology
addressed with an iterative and incremental software process
Parallel development at all the three levels
(domain decomposition)

23. Biological processes Known, available Unknown, not available
Physical processes
Biological processes
Known,
available
Unknown,
not available
Courtesy A. Brahme (KI)
E.g. generation of free radicals in the cell
Chemical processes
Courtesy A. Brahme (Karolinska Institute)

24. Theories and models for cell survival
Cellular level
Theories and models for cell survival
TARGET THEORY MODELS
Single-hit model
Multi-target single-hit model
Single-target multi-hit model
MOLECULAR THEORY MODELS
Theory of radiation action
Theory of dual radiation action
Repair-Misrepair model
Lethal-Potentially lethal model
Geant4 approach: variety of models all handled through the same abstract interface
in progress
Critical evaluation of the models
Analysis & Design
Implementation
Test
Requirements
Problem domain analysis
Experimental validation of Geant4 simulation models

25. Target theory models Multi-target single-hit model Single-hit model
No hits: cell survives
One or more hits: cell dies
Extension of single-hit model
Multi-target
single-hit
model
Single-hit
model
Cell survival equations based on
model-dependent assumptions
PSURV(q,b,n,D) = B(b) (e-qD)(n-b) (1- e-qD)b n!
b! (n -b)!
S(ρ,Δ) = PSURV (ρ0, h=0, Δ) = (1- ρ0)Δ = exp[Δ ln (1- ρ0)]
Single-target
multi-hit
model
No assumption on:
Time
Enzymatic repair of DNA
Joiner & Johns
model
S= e-ßD 2
S = e-αR [1 + ( αS / αR -1) e ] D – ß D
- D/DC
two hits

26. Molecular models for cell death
More sophisticated models
Molecular theory
of radiation action
(linear-quadratic model)
Theory of dual
radiation action
Chadwick and Leenhouts (1981)
Kellerer and Rossi (1971)
Lethal-potentially
lethal model
Repair or misrepair
of cell survival
Tobias et al. (1980)
Curtis (1986)

27. In progress: evaluation of model parameters from clinical data
TARGET
THEORY
SINGLE-HIT
MULTI-TARGET
MOLECULAR
RADIATION ACTION
DUAL RADIATION ACTION
REPAIR-MISREPAIR
LIN REP / QUADMIS
LIN REP / MIS
LETHAL-POTENTIALLY LETHAL
LETHAL-POTENTIALLY LETHAL – LOW DOSE
LETHAL-POTENTIALLY LETHAL – HIGH DOSE
LETHAL-POTENTIALLY LETHAL – LQ APPROX
S= e-D / D0
REVISED MODEL
S = 1- (1- e-qD)n
S = e-q1D [ 1- (1- e-qn D)n ]
S = e –p ( αD + ßD ) 2
In progress: evaluation of model parameters from clinical data
S = S0 e - k (ξ D + D ) 2
S = e-αD[1 + (αDT / ε)]ε
S = e-αD[1 + (αD / ε)]εΦ
S = exp[ - NTOT[ ]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]

28. Low Energy Physics extensions
DNA level
Low 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
b-release winter 2006
Processes for other material than water to follow
interest for radiation effects on components
Current status

29. Development process Complex domain Collaboration with theorists
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!

30. Cross sections
Process kinematics
Final state generation

31. Elastic scattering Preliminary Total cross section
Brenner
Emfietzoglou
Phys. Med. Biol. 45 (2000)
Solid line: our model
Preliminary
Angular distribution
10 eV
100 eV
200 eV
500 eV
1 keV
J. Phys. D 33 (2000)

32. Excitation Preliminary Testing still in progress p + H20  p + H20*
s(m2)
E(eV)
p + H20  p + H20*
Preliminary
Rad. Phys. Chem. 59 (2000)
s(m2)
E(eV)
e- + H20  e- + H20*
Testing still in progress

33. Excitation Preliminary He + H2O  He + H2O* He+ + H2O  He+ + H2O*
Rad. Phys. Chem. 59 (2000)
s(m2)
E(eV)
He + H2O  He + H2O*
He+ + H2O  He+ + H2O*
He++ + H2O  He++ + H2O*
s(m2)
Preliminary
E(eV)

34. Charge transfer Preliminary p + H20  H + H20+ + E
s(m2)
Preliminary
p + H20  H + H20+ + E
H + H20  p + e- + H20
Helium
E(eV)
Charge transfer by protons/Hydrogen is implemented
Charge transfer by Helium is still to be implemented

35. Ionisation Preliminary H + H20  H + e- + H20+ p + H20  p + e- + H20+
s(m2)
Preliminary
H + H20  H + e- + H20+
p + H20  p + e- + H20+
ln(E/eV)
Proton (< 500 keV) and Hydrogen ionisation implemented Development of remaining ionisation processes still ongoing

36. Scenario for Mars (and earth…)
Geant4 simulation with biological processes at cellular level (cell survival, cell damage…)
Geant4 simulation
treatment source +
geometry from CT image or
anthropomorphic phantom
Geant4 simulation
space environment +
spacecraft, shielding etc.
anthropomorphic phantom
Dose in organs at risk
Oncological risk to astronauts/patients
Risk of nervous system damage
Phase space input to nano-simulation
Geant4 simulation with
physics at eV scale +
DNA processes

37. Conclusions
Geant4 offers powerful geometry and physics modelling in an advanced computing environment
Wide spectrum of complementary and alternative physics models
Multi-disciplinary applications of dosimetry simulation
Precision 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