Download Geant4 Space Workshop - 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
DNA
MICROS 2005
Venezia, 13-18 November 2005
Maria Grazia Pia, INFN Genova
Object Oriented Toolkit for
the simulation of particle
interactions with matter
also…
An experiment of
distributed software production
and management
An experiment of application of rigorous
software engineering methodologies
and Object Oriented technology
to particle physics environment
Maria Grazia Pia, INFN Genova
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
in a nutshell
Geant4 architecture
Rigorous software engineering
Interface to
external
products w/o
dependencies
Domain
decomposition
– spiral software process
– object oriented methods
– quality assurance
– use of standards
Geometry
hierarchical
structure of subdomains
Uni-directional
flow of
dependencies
– 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
Maria Grazia Pia, INFN Genova
– visualisation, UI/GUI
– multiple drivers to external systems w/o
introducing dependencies
~80 members
Geant4 Collaboration
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.
Maria Grazia Pia, INFN Genova
Dosimetry with Geant4
Wide spectrum of physics coverage, variety of models
Precise, quantitatively validated physics
Accurate description of geometry and materials
Multi-disciplinary
application environment
Space science
Radiotherapy
Maria Grazia Pia, INFN Genova
Effects on components
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
Radiation
Protection
Maria Grazia Pia, INFN Genova
Courtesy of J. Perl, SLAC
Hadrontherapy
Courtesy of S. Guatelli et al,. INFN Genova
Brachytherapy
Courtesy of L. Beaulieu et al., Laval
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
Lateral profile
6MV – 10x10 field – 50mm depth
range
D
p-value
-84  -60 mm
0.39
0.23
-59  -48 mm
0.27
0.90
-47  47 mm
0.43
0.19
48  59 mm
0.30
0.82
60 Maria
 84 mm
0.10
Grazia Pia, 0.40
INFN Genova
Percent dose
Kolmogorov-Smirnov Test
Distance (mm)
IMRT Treatment Head
Dosimetry: protons and ions
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
Electromagnetic only
0.52
agreement with data
better than 3%
0.443831
Inventory of Geant4 hadronic models
Maria Grazia Pia, INFN Genova
Radiation protection for
interplanetary manned missions
Maria Grazia Pia, INFN Genova
Doubling the shielding
thickness decreases the
energy deposit by ~10%
10 cm water
5 cm water
rigid/inflatable
habitats are equivalent
2.15 cm Al
e.m. physics + Bertini set
5 cm water
10 cm water
Maria Grazia Pia, INFN Genova
4 cm Al
shielding
materials
e.m.
physics
only
10 cm water
10 cm polyethylene
A major concern in radiation protection is the
dose accumulated in organs at risk
Anthropomorphic
Phantoms
Development of anthropomorphic
phantom models for Geant4
– evaluate dose deposited in critical organs
Original approach
– analytical and voxel phantoms in
the same simulation environment
Analytical phantoms
Geant4 CSG, BREPS solids
Voxel phantoms
Geant4 parameterised volumes
GDML
Maria Grazia Pia, INFN Genova
for geometry description storage
Effects of external shielding
Self-body shielding
Maria Grazia Pia, INFN Genova
Skull
Upper spine
Lower spine
Arm bones
Leg bones
Womb
Stomach
Upper intestine
Lower intestine
Liver
Pancreas
Spleen
Kidneys
Bladder
Breast
Overies
Uterus
Skull
Upper spine
Lower spine
Arm bones
Leg bones
Womb
Stomach
Upper intestine
Lower intestine
Liver
Pancreas
Spleen
Kidneys
Bladder
Breast
Overies
Uterus
Radiation exposure
of astronauts
5 cm water shielding
10 cm water shielding
Dose calculation in critical organs
Geometry objects
(solids, logical volumes, physical volumes)
are handled transparently by
Geant4 kernel through
So why not describing
DNA?
abstract interfaces
Processes are handled
transparently by Geant4 kernel
through an
abstract interface
So what about
mutagenesis as a
process?
DNA
Object Oriented technology
+
Geant4 architecture
Maria Grazia Pia, INFN Genova
Biological models in Geant4
Relevance for space:
astronaut and aircrew radiation hazards
Maria Grazia Pia, INFN Genova
DNA
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: 2000-2001
– Collection of user requirements & first prototypes
Second phase: started in 2004
– Software development & public, open source release
Maria Grazia Pia, INFN Genova
Multiple domains in the
same software environment
Macroscopic level
– calculation of dose
– already feasible with Geant4
– develop useful associated tools
Complexity of
software, physics and biology
Cellular level
addressed with an iterative and
incremental software process
– 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.
Maria Grazia Pia, INFN Genova
Parallel development
at all the three levels
(domain decomposition)
http://www.ge.infn.it/geant4/dna
Maria Grazia Pia, INFN Genova
Biological processes
Physical
processes
Biological
processes
Known,
available
Courtesy A. Brahme (KI)
Unknown,
not available
Courtesy A. Brahme
Maria Grazia
Pia, INFN Genova
(Karolinska
Institute)
E.g. generation
Chemical of free rad
icals
processes in the cell
Cellular level
Theories and models for cell survival
TARGET THEORY MODELS
 Single-hit model
 Multi-target single-hit model
 Single-target multi-hit model
Geant4 approach: variety of
models all handled through
the same abstract interface
MOLECULAR THEORY MODELS
 Theory of radiation action
 Theory of dual radiation action
 Repair-Misrepair model
 Lethal-Potentially lethal model
Critical evaluation of the models
Requirements
Problem domain analysis
Maria Grazia Pia, INFN Genova
in progress
Analysis & Design
Implementation
Test
Experimental validation of
Geant4 simulation models
Target theory models
Extension of single-hit model
No hits: cell survives
One or more hits: cell dies
Single-hit
model
Multi-target
single-hit
model
Cell survival equations
based on
model-dependent
assumptions
PSURV(q,b,n,D) = B(b)
(e-qD)(n-b)
(1-
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
2
S= e-ßD
two hits
Maria Grazia Pia, INFN Genova
n!
e-qD)b
S=
Joiner & Johns
model
- D/DC
e-αR [1 + ( αS / αR -1) e
]D–ßD
Molecular models for cell death
More sophisticated models
Molecular theory
of radiation action
(linear-quadratic model)
Chadwick and Leenhouts (1981)
Repair or misrepair
of cell survival
Tobias et al. (1980)
Maria Grazia Pia, INFN Genova
Theory of dual
radiation action
Kellerer and Rossi (1971)
Lethal-potentially
lethal model
Curtis (1986)
TARGET
THEORY
SINGLE-HIT
TARGET
THEORY
MULTI-TARGET
SINGLE-HIT
S= e-D / D0
REVISED MODEL
MOLECULAR RADIATION ACTION
THEORY
S = 1- (1- e-qD)n
S = e –p ( αD + ßD
S = e-q1D [ 1- (1- e-qn D)n ]
2
)
In progress:
evaluation of
model
parameters
from clinical
data
MOLECULAR DUAL RADIATION
ACTION
THEORY
S = S0 e
MOLECULAR REPAIR-MISREPAIR
THEORY
LIN REP / QUADMIS
S = e-αD[1 + (αDT / ε)]ε
MOLECULAR REPAIR-MISREPAIR
THEORY
LIN REP / MIS
S = e-αD[1 + (αD / ε)]εΦ
MOLECULAR LETHAL-POTENTIALLY
LETHAL
THEORY
NPL
S = exp[ - NTOT[1 + ε (1 – e- εBAtr) ]ε ]
MOLECULAR LETHAL-POTENTIALLY
LETHAL – LOW DOSE
THEORY
S = e-ηAC D
MOLECULAR LETHAL-POTENTIALLY
LETHAL – HIGH DOSE
THEORY
- ln[ S(t)] = (ηAC + ηAB) D – ε ln[1 + (ηABD/ε)(1 – e-εBA tr)]
MOLECULAR LETHAL-POTENTIALLY
LETHAL – LQ APPROX
THEORY
- ln[ S(t)] = (ηAC + ηAB e-εBAtr ) D + (η2AB/2ε)(1 – e-εBA tr)2 D2]
Maria Grazia Pia, INFN Genova
2
- k (ξ D + D )
Low Energy Physics extensions
DNA level
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
Details: see poster presentation
Processes for other material than water to follow
Electrons
Elastic
Brenner (7.5 - 200 eV)
Emfietzoglou (> 200 ev)
Protons (H+) Hydrogen (H) Alpha (He++)
Negligible effect
Negligible effect
He+
He
Negligible effect
Negligible effect
Negligible effect
Miller and Green
Miller and Green
Miller and Green
(1 keV – 15 MeV)
(1 keV – 15 MeV)
(1 keV – 15 MeV)
In progress
In progress
Not pertinent to this
particle
Excitation
Emfietzoglou
Miller and Green
Born (7 ev – 10 keV)
Born (100 eV – 10 MeV)
Charge decrease
Not pertinent to this
particle
Dingfelder
(100 eV – 2 MeV)
Not pertinent to this
particle
Charge increase
Not pertinent to this
particle
Not pertinent to this
particle
Miller and Green
Dingfelder
(0.1 Kev – 100 MeV)
Not pertinent to this
particle
In progress
In progress
Rudd (0.1 – 100 MeV)
In progress
In progress
In progress
Ionization
In progress
Maria Grazia Pia, INFN Genova
Rudd (0.1 - 500 keV)
In progress (> 500 keV)
Negligible effect
Scenario
for Mars (and Earth…)
Geant4 simulation
space
environment
treatment
source
+
spacecraft,from
shielding
etc.
geometry
CT image
+
or
anthropomorphic phantom
Dose in organs
at risk
Geant4 simulation
with biological
processes at cellular
level (cell survival,
cell damage…)
Oncological risk to
astronauts/patients
Risk of nervous
system damage
Phase-space input
to nano-simulation
Maria Grazia Pia, INFN Genova
Geant4 simulation with
physics at eV scale
+
DNA processes
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
Maria Grazia Pia, INFN Genova