Applications in Medicine

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


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


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


Mars and LeukemiaMars and Leukemia

Symposium on Geant4 Applications

9th ICATPP ConferenceComo, 17-21 October 2005

Maria Grazia Pia

INFN Sezione di 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


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


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


Radiation environmentRadiation environment


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


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


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


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


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


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


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


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


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


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


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


G4LadyG4Lady


ApplicatioApplicationn

5 cm water shielding

Sku

llU

pp

er

spin

e

Lo

we

r sp

ine

Arm

bo

ne

sL

eg

bo

ne

sW

om

bS

tom

ach

Up

pe

r in

test

ine

Lo

we

r in

test

ine

Liv

er

Pa

ncr

ea

sS

ple

en

Kid

ne

ysB

lad

de

rB

rea

stO

verie

sU

teru

s

10 cm water shielding

Sku

llU

pp

er

spin

e

Lo

we

r sp

ine

Arm

bo

ne

sL

eg

bo

ne

sW

om

bS

tom

ach

Up

pe

r in

test

ine

Lo

we

r in

test

ine

Liv

er

Pa

ncr

ea

sS

ple

en

Kid

ne

ysB

lad

de

rB

rea

stO

verie

sU

teru

s

Dose calculation in critical organs

Effects of external shieldingexternal shieldingSelf-body shieldingSelf-body shielding


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


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


Geant4 Symposium 2015Geant4 Symposium 2015

Study of radiation damage at the cellular and DNA level

DNADNA


http://www.ge.infn.it/geant4/dnahttp://www.ge.infn.it/geant4/dna


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


Biological models in Geant4 Biological models in Geant4

Relevance for space: Relevance for space: astronaut and aircrew radiation hazardsastronaut and aircrew radiation hazards


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


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


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


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


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


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)


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


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

Applications in Medicine

Documents