Maria Grazia Pia, INFN Genova
Applications in MedicineApplications in Medicine
Symposium on Geant4 Applications
9th ICATPP ConferenceComo, 17-21 October 2005
Maria Grazia Pia
INFN Sezione di Genova
Maria Grazia Pia, INFN Genova
Thanks to Simone Gianifor organizing this symposium!
GEANT4 SYMPOSIUM PROGRAMME20 Oct 2005
INDUSTRYThe Radiation Imager Virtual LaboratoryGENERAL ELECTRICS – by R.ThompsonMonteCarlo Simulation of PET SystemsSIEMENS - CPS – by M.Conti
SPACEApplications of G4 for the ESA Space ProgrammeEUROPEAN SPACE AGENCY – by G.SantinGEANT4 Applications for NASA Space MissionsSLAC - NASA GSFC - Vanderbilt U. – by M.Asai
MEDICINEG4 in Development of New Radiotherapy TreatmentsKAROLINSKA (Sweden) – by A.BrahmeGEANT4 Applications in MedicineINFN (Italy) – by M.G.Pia
TECHNOLOGYGEANT4 Application to Ion-Therapy in JapanKEK (Japan) – by K.AmakoOpen-GATE ProjectINSERM (France) – by I.Buvat
PHYSICSDetector Simulation in HEPCERN (CH) – by J.P.WellischGEANT4 Accelerator ApplicationsIMPERIAL COLLEGE (UK) – by M.Ellis
Maria Grazia Pia, INFN Genova
MedicalMedical applicationsapplications
Courtesy of L. Beaulieu et al., Laval
Radiotherapy with external beams, IMRT
Brachytherapy
PET, SPECT
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 B. Mascialino et al., INFN Genova
Courtesy of GATE Collaboration
Maria Grazia Pia, INFN Genova
Mars and LeukemiaMars and Leukemia
Symposium on Geant4 Applications
9th ICATPP ConferenceComo, 17-21 October 2005
Maria Grazia Pia
INFN Sezione di Genova
Maria Grazia Pia, INFN Genova
AstrophysicsAstrophysics
Planetary exploration has grown into a major player in the vision of space science organizations like ESA and NASA
The study of the effects of space radiation on astronauts is an important concern of missions for the human exploration of the solar system
The radiation hazard can be limited:– selecting traveling periods and trajectories – providing adequate shielding in the transport vehicles and surface habitats
Radiation Protection
Maria Grazia Pia, INFN Genova
Vehicle conceptsVehicle concepts
Materials and thicknesses by ALENIA SPAZIO
A multilayer structure consisting of: MLI: external thermal protection blanket
- Betacloth and Mylar
Meteoroid and debris protection- Nextel (bullet proof material) and open cell foam
Structural layer- Kevlar
Rebundant bladder- Polyethylene, polyacrylate, EVOH, kevlar, nomex
SIH - Simplified Inflatable Habitat
Conventional approach
Rigid HabitatRigid HabitatA layer of Al (structure element of the ISS)
Innovative concepts under study
Inflatable habitatInflatable habitat
Maria Grazia Pia, INFN Genova
Surface HabitatsSurface Habitats
Sketch by ALENIA SPAZIO
Cavity in the planetary soil
+
Covering heap
Innovative concepts under study
Use of local materialsUse of local materials
Maria Grazia Pia, INFN Genova
Radiation environmentRadiation environment
Maria Grazia Pia, INFN Genova
PhysicsPhysics– Select appropriate models models from the Geant4 Toolkit– Verify the accuracyaccuracy of the physics models – Distinguish e.m. and hadronic contributions to the dose
Radiation protection with Radiation protection with
Electromagnetic processes
+ Hadronic processes
Model the radiation spectrum according to current standards– Galactic cosmic rays, Solar particle events
Evaluate energy deposit/doseenergy deposit/dose in shielding configurations– various shielding materials and thicknesses
Vehicle concepts
Surface habitats
Astronaut
Geometrical Geometrical configurationsconfigurations– Model essential characteristicsessential characteristics for dosimetry studies– Model complex geometries of spacecrafts in detail
Maria Grazia Pia, INFN Genova
Geant4 EM Physics ModelsGeant4 EM Physics Models
Verification of the Geant4 e.m. physics processes with respect to
protocol dataprotocol data (NIST reference data, ICRU Report 49)
Geant4 electromagnetic physics models are accurate
Compatible with NIST data within NIST accuracy (LowE p-value > 0.9)
“Comparison of Geant4 electromagnetic physics models against the NIST reference data” IEEE Transactions on Nuclear Science, vol. 52 (4), pp. 910-918, 2005
Optimal selection
Geant4 Low Energy Package for p, , ions and their secondaries
Geant4 Standard Package for positrons
Maria Grazia Pia, INFN Genova
Intrinsic complexity of hadronic physicsAmple choice of models
Composition of different models over an extended energy rangeto cover the spectrum of galactic cosmic rays and solar particle events
Geant4 Hadronic PhysicsGeant4 Hadronic Physics
Complementary and alternative models
Parameterised, data driven and theory driven models
The most complete hadronic simulation kit available on the market
Models for p and Hadronic models for ions in progress
Maria Grazia Pia, INFN Genova
DosimetryDosimetry
The phantom is the volume where the energy deposit is collected– The energy deposit is given by the primary particles and all the secondaries created
30 cm Z
The Astronaut is approximated as a phantom– a water box, sliced along the longitudinal axis to evaluate
particle penetration in the body
– the transversal size is optimized to contain the shower generated by the interacting particles
– the longitudinal size is a “realistic” human body thickness
Distance (mm)
Per
cent
dos
e
Lateral profile6MV – 10x10 field – 50mm depth
IMRT Treatment Head
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
Maria Grazia Pia, INFN Genova
Strategy against SPEStrategy against SPE
SPE p and with E > 130 MeV/nucl reach the shelter with E > 400 MeV/nucl reach the phantom
(i.e. < 0.3% of the entire spectrum)
The shelter shields ~ 50% of the dose by GCR p ~ 67 % of the dose by GCR α
escaping the main shielding
Energy deposit (MeV) with respect to the depth in the phantom (cm)
Shelter
SIH
A shelter with additional water shielding
(75 cm thickness)
99.7%99.7% of the SPE spectrum
is shielded
Maria Grazia Pia, INFN Genova
Planetary surface habitats Planetary surface habitats
x vacuum
moonsoil
Phantom
x = 0 - 3 m roof thickness
Energy deposit (GeV) in the phantom vs roof thickness (m)
4 cm Al
4 cm Al
GCR pGCR α
e.m. + hadronic physics (Bertini set)
Moon as an intermediate step in the exploration of Mars
Habitat built out of moon soil
Habitat
A log of moon soil is as effective as Al shielding, or even better
Maria Grazia Pia, INFN Genova
Dosimetry with Geant4 Dosimetry with Geant4
All the previous results are novel radiation protection applications of Geant4
– first quantitative evaluation of space radiation effects for interplanetary manned missions based on 3D Monte Carlo calculations
– first quantitative comparison of innovative shielding concepts w.r.t. conventional solutions
Key Geant4 features– wide spectrum of physics coverage– precise, quantitatively validated physics models selected as the most
appropriate for the application– accurate description of materials
Same key features as in dosimetry for medical applicationsdosimetry for medical applications
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
– mix & matchmix & match– facilitated by the OO technology
First release December 2005– G. Guerrieri, Thesis, Univ. Genova, Oct. 2005
Maria Grazia Pia, INFN Genova
Analytical phantomsAnalytical phantomsGeant4 CSG, BREPS solids
Voxel phantomsVoxel phantomsGeant4 parameterised volumes
GDMLGDML for geometry description storage
Sound software technologysoftware technology and
rigorous software processsoftware process
Maria Grazia Pia, INFN Genova
Current implementation
ORNL and MIRD5 phantomsMale and Female
Geant4 analytical phantomORNL model, female
1 skull2 thyroid3 spine4 lungs5 breast6 heart7 liver8 stomach9 spleen10 kidneys11 pancreas12 intestine13 uterus and ovaries14 bladder15 womb16 leg bones17 arm bones
Geant4 analytical phantomsGeant4 analytical phantoms
Maria Grazia Pia, INFN Genova
G4LadyG4Lady
Maria Grazia Pia, INFN Genova
ApplicatioApplicationn
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 shieldingSelf-body shieldingSelf-body shielding
Maria Grazia Pia, INFN Genova
Total Body Irradiation Total Body Irradiation
TBITBI is used as a method of preparation for bone marrow transplantation for leukemiasleukemias and lymphomaslymphomas
Low dose TBILow dose TBI is sometimes used to treat disorders of the blood cellsdisorders of the blood cells such as low grade lymphoma and does not require bone marrow transplant or stem cells
In TBI, the dose calculation is based on dosimetrydosimetry using a phantomphantom
opens new ground for precise dose calculation and TBI optimisationTBI optimisation
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
Precise physicsRigorous validation
Maria Grazia Pia, INFN Genova
Geant4 Symposium 2015Geant4 Symposium 2015
Study of radiation damage at the cellular and DNA level
DNADNA
Maria Grazia Pia, INFN Genova
http://www.ge.infn.it/geant4/dnahttp://www.ge.infn.it/geant4/dna
Maria Grazia Pia, INFN Genova
Geant4-based “sister” activity to the Geant4 Low-Energy Electromagnetic Working Group
– 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 & 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
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
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 radfree rad icals icals in the cellin the cell
Maria Grazia Pia, INFN Genova
RequirementsProblem domain analysis
Theories and models for cell survivalTheories and models for cell survivalTARGET 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
done
in progress
Cellular level Cellular level Cellular level Cellular level
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: calculation of
model parameters from clinical
data
Maria Grazia Pia, INFN Genova
Low Energy Physics extensionsLow Energy Physics extensions
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
Status: first release in December 2005
DNA levelDNA levelDNA levelDNA level
Maria Grazia Pia, INFN Genova
Scenario Scenario for Mars (and hospitals)for Mars (and hospitals)
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
for medicinefor medicine
Macroscopic – 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– processes for DNA strand breaking, 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
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
ThanksThanks
Riccardo Capra, Susanna Guatelli, Giorgio Guerrieri, Barbara Mascialino, Michela Piergentili (INFN Genova)
Petteri Nieminen (ESA)
Alenia Spazio (Torino)
Sébastien Incerti, Philippe Moretto (CENBG)
Ziad Francis, Gérard Montarou (Univ. Clermont-Ferrand)
Stéphane Chauvie (INFN Torino)
Joseph Perl (SLAC)
Thanks to many Geant4 users worldwide, even if not all their Geant4 applications in medicine were mentioned in this presentation
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