Maria Grazia Pia, INFN Genova - Como 2001 From HEP computing to bio-medical research and vice versa Simulation software: applications and results in the

Maria Grazia Pia, INFN Genova - Como 2001

Simulation software: applications and results in the bio-medical

domain

From HEP computing to bio-medical From HEP computing to bio-medical research research

and vice versaand vice versa

Maria Grazia PiaINFN - Sezione di Genova, Italy

…with contributions from many users

VII International Conference on Advanced Technologies and Particle Physics

Como, 16 October 2001

S. Agostinelli, S. Chauvie, G. Cosmo, F.Foppiano, S. Garelli, F. Marchetto, P. Nieminen, P. Rodrigues, R. Taschereau, A. Trindade, M. Tropeano


Globalisation

Sharing requirements and functionalities

across diverse fields


Requirements for LowE p in Requirements for LowE p in

UR 2.1 The user shall be able to simulate electromagnetic interactions of positive charged hadrons down to < 1 KeV.

Need: Essential

Priority: Required by end 1999

Stability: T. b. d.

Source: Medical physics groups, PIXE

Clarity: Clear

Verifiability: Verified

GEANT4 LOW ENERGY ELECTROMAGNETIC PHYSICS

GGEEAANNTT44 LLOOWW EENNEERRGGYY

EELLEECCTTRROOMMAAGGNNEETTIICC PPHHYYSSIICCSS

User Requirements Document Status: in CVS repository

Version: 2.4 Project: Geant4-LowE Reference: LowE-URD-V2.4 Created: 22 June 1999 Last modified: 26 March 2001 Prepared by: Petteri Nieminen (ESA) and Maria Grazia Pia (INFN)


LowE Hadrons and ionsLowE Hadrons and ions

OOAD… OOAD…


……and validationand validation

Courtesy of R. Gotta, Thesis

INFN-Torino medical physics group

Geant4 LowE Working Group

Experimental data: Bragg peak

• dataO simulation

Test set-up at PSI


What could be the source of What could be the source of detector damage?detector damage?

Chandra X-ray Observatory Status Update

September 14, 1999 MSFC/CXC

CHANDRA CONTINUES TO TAKE SHARPEST IMAGES EVER; TEAM STUDIES INSTRUMENT DETECTOR CONCERN

Normally every complex space facility encounters a few problems during its checkout period; even though Chandra’s has gone very smoothly, the science and engineering team is working a concern with a portion of one science instrument. The team is investigating a reduction in the energy resolution of one of two sets of X-ray detectors in the Advanced Charge-coupled Device Imaging Spectrometer (ACIS) science instrument. A series of diagnostic activities to characterize the degradation, identify possible causes, and test potential remedial procedures is underway. The degradation appeared in the front-side illuminated Charge-Coupled Device (CCD) chips of the ACIS. The instrument’s back-side illuminated chips have shown no reduction in capability and continue to perform flawlessly.

Radiation belt electrons?

Scattered in the mirror shells?

Effectiveness of magnetic “brooms”?

Electron damage mechanism? - NIEL?

Other particles? Protons, cosmics?

Courtesy of R. Nartallo, ESA

XMM-Newton


CCD displacement damage: front CCD displacement damage: front vs. back-illuminated.vs. back-illuminated.

30 m 2 m30 m2 m

30 30 m Si m Si ~1.5 MeV p ~1.5 MeV protonsrotons

Active layerActive layerPassive layerPassive layer ““Electron Electron

deflector”deflector”

Variation in Efficiency with Proton Energy at various source half-angles

1.E-09

1.E-08

1.E-07

1.E-06

1.E-05

1.E-04

0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5

Proton Energy (MeV)

Eff

icie

ncy

EPIC 0.5 deg

EPIC 1 deg

EPIC 4 deg

EPIC 2 deg

EPIC 10 deg

EPIC 30 deg

RGS 0.5 deg

RGS 1 deg

RGS 2 deg

RGS 4 deg

RGS 10 deg

RGS 30 deg

EPICEPIC

RGSRGS

ESA Space Environment & Effects Analysis Section

Courtesy of

Low-E Low-E (~100 keV to few MeV)(~100 keV to few MeV), low-angle , low-angle (~0°-5°) (~0°-5°) proton scatteringproton scattering


What happened next?What happened next?

XMM was launched on 10 December 1999 from Kourou EPIC image of the two flaring Castor

components and the brighter YY GemCourtesy of


……and the other way roundand the other way round

Maria Grazia Pia, INFN Genova - Como 2001 Courtesy ESA Space Environment & Effects Analysis Section

X-Ray Surveys of X-Ray Surveys of Planets, Planets, Asteroids and MoonsAsteroids and Moons

Induced X-ray line emission:indicator of target composition(~100 m surface layer)

Cosmic rays,jovian electrons

Geant3.21

ITS3.0, EGS4

Geant4

Solar X-rays, e, p

Courtesy SOHO EIT

C, N, O line emissions included

Low energy e, Low energy e, extensions extensions

…were triggered by astrophysics requirements


Scattered

photons

Fe lines

GaAs lines

Based on EPDL97, EEDL and EADL evaluated data libraries- cross sections- sampling of the final state

250 eV up to 100 GeV250 eV up to 100 GeV

Low Energy Processes: e,


0.01 0.1 1 100.01

0.1

1

10

100

1000

Geant4 LowEn NIST

/ (

cm 2

/g)

in ir

on

Photon Energy (MeV)

0.01 0.1 1 10

0.1

1

10

Geant4 LowEn NIST

/

(cm

2 /g

) in

wat

er

Photon Energy (MeV)

0.01 0.1 1 10-16

-14

-12

-10

-8

-6

-4

-2

0

2

4

6

8

10

12

14

16

Delta = (NIST-G4EMStand) / NIST Delta = (NIST-G4LowEn) / NIST

Del

ta (

%)

Photon Energy (MeV)

0.01 0.1 1

0.01

0.1

1

10

100

Geant4 LowEn NIST

/ (

cm 2

/ g

in le

ad

Photon energy (MeV)

0.01 0.1 1-10

-8

-6

-4

-2

0

2

4

6

8

10 E = (NIST - G4EM Standard)/NIST E = (NIST- G4LowEn)/NIST

E (

%)

Photon Energy (MeV)

Photon attenuation: vs. NIST Photon attenuation: vs. NIST datadata

water Fe Pb

0.01 0.1 1 10-18-16-14-12-10-8-6-4-202468

1012141618

E = (NIST-G4EMStandard)/NIST E = (NIST-G4LowEn)/NIST

E (

%)

Photon Energy (MeV)

Courtesy of S. Agostinelli, R. Corvo, F. Foppiano, S. Garelli, G. Sanguineti, M. Tropeano

Testing and Validation by IST - Natl. Inst. for Cancer Research, Genova


……the first user applicationthe first user application

Seedcomponents

Silver core (250 µm)

Titanium shell (50 µm)

Iodine-125 seed

4.5 mm

Distance (nm)

GEANT4

Terrisol

keV/µm

10 keV electron in water

R. Taschereau, R. Roy, J. Pouliot

Centre Hospitalier Universitaire de Quebec, Dept. de radio-oncologie, Canada

Univ. Laval, Dept. de Physique, Canada

Univ. of California, San Francisco, Dept. of Radiation Oncology, USA

Exploiting X-ray fluorescence to lower the energy spectrum of photons (and electrons) and enhance the RBE

Titanium encapsulated 125I sources in permanent prostate implants


……and the same requirements in HEP tooand the same requirements in HEP too

Similar requirements on both low energy e/ and hadrons, K-shell transitions etc. from “underground” HEP experiments collected ~1 year later

Recent interest on these physics models from LHC for precision detector simulation

They profit of the fact that the code

- does already exist,

- has been extensively tested

- and experimentally validated by other groups


A lesson to learn

What may look far from the scope of HEP today,

may be required as an essential functionality

tomorrow

Open mind…


What can HEP propose?

ToolsMethodologies


The transparency of physics

Advanced functionalities in geometry, physics, visualisation etc.

Extensibility to accomodate new user requirements (thanks

to the OO technology)

Adoption of standards wherever available (de jure or de facto)

Use of evaluated data libraries

Quality Assurance based on sound

software engineering

Independent validation by a large user

community worldwide

User support from experts

What in a simulation

software system is relevant to the

bio-medical community?

A rigorous software process

Specific facilities controlled by a friendly UI


Physics Physics requirementsrequirements

e,down to 250 eV (EGS4, ITS to 1 keV, Geant3 to 10 keV)

Many new physics features w.r.t. Geant3

Fundamental also to HEP/astroparticle

experiments Hadron and ion electromagnetic models

based on Ziegler and ICRU data and parameterisations

Based on EPDL97, EEDL and EADL evaluated data libraries

Bragg peak

shell effects

ionsGeant4Geant3data

And much more: fluorescence radioactive decay hadronic models etc…

And many relevant functionalities in other domains too, not only physics!

New multiple scattering model


Guidelines for physicsGuidelines for physics

From the Minutes of LCB (LHCC Computing Board) meeting on 21 October, 1997:

Physics open to Physics open to evolutionevolution

with attention to UR

facilitated by the OO technology

“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.”

The transparency of the physics implementation: The transparency of the physics implementation: fundamental for “sensitive”applications, such as fundamental for “sensitive”applications, such as medical onesmedical ones


Domain decomposition

hierarchical structure of

sub-domains

Geant4 architecture

Uni-directional flow of

dependencies

Software Engineering

plays a fundamental role in Geant4

User Requirements• formally collected• systematically updated• PSS-05 standard

Software Process• spiral iterative approach• regular assessments and improvements• monitored following the ISO 15504 model

Quality Assurance• commercial tools• code inspections• automatic checks of coding guidelines• testing procedures at unit and integration level• dedicated testing team

Object Oriented methods• OOAD• use of CASE tools

• essential for distributed parallel development• contribute to the transparency of physics

Use of Standards • de jure and de facto


Applications

Verification of conventional radiotherapy treatment

planning (as required by protocols)

Investigation of innovative methods in radiotherapy

Radiodiagnostics


3 m m ste e l c a b le

5.0 m m

0.6 m m

3.5 m m

1.1 m m

Ac tive Ir-192 C o re

The IST group follows the direction of Basic Dosimetry on Radiotherapy with Brachytherapy Source of the Italian Association of Biomedical Physics (AIFB)

BrachytherapyBrachytherapy

Brachytherapy is a medical therapy used for cancer treatment

Radioactive sources are used to deposit therapeutic doses near tumors, while preserving surrounding healthy tissues Strict protocols Strict protocols

Protocols require testing the treatment planning systems


0 10 20 30 40 500,0

0,2

0,4

0,6

0,8

1,0

1,2 Simulazione Nucletron Misure

Dose %

Distanza lungo Z (mm)Distance along Z (mm)

SimulationNucletronData

-60

-55

-50

-45

-40

-35

-30

-25

-20

-15

-10

-5

0-40 -30 -20 -10 0 10 20 30 40

Distanza trasversale (mm)

80% 60% 40% 20% 10%

Pro

fon

dità

(m

m)

Transverse distance (mm)

De

pth

(m

m)

Experimental validationLeipzig applicators

Courtesy F. Foppiano, M. Tropeano

BrachytherapyBrachytherapy at the Natl. Inst. for Cancer Research (IST-Genova)

Superficial brachytherapy


Source anisotropy

Especially for uterus, vagina and lung cancer

Treatment planning systems include algorithms to account for source anisotropy

Endocavitary Endocavitary brachytherapybrachytherapy


-40 -30 -20 -10 0 10 20 30 400,0

0,5

1,0

1,5

2,0

2,5

Simulazioni Plato Misure

Dos

e %

Distanza lungo X (mm)Distance along X (mm)

SimulationPlatoData

-40 -30 -20 -10 0 10 20 30 400,0

0,5

1,0

1,5

2,0

2,5 Simulazioni Plato

Dos

e %

Distanza lungo Z (mm)Distance along Z (mm)

SimulationPlato

Longitudinal axis of the sourceLongitudinal axis of the source

Difficult to make direct measurements

rely on simulation to get better accuracy than conventional treatment planning software

Effects of source anisotropy

Transverse axis of the sourceTransverse axis of the source

Comparison with experimental data

validation of the software

Role of the simulation:Role of the simulation:

Courtesy F. Foppiano, M. Tropeano

precise evaluation of the effects of source anisotropy in the dose


Courtesy of S. Agostinelli, R. Corvo, F. Foppiano, S. Garelli, G. Sanguineti, M. Tropeano, IST Genova

Source anisotropySource anisotropy

Plato treatment planning

-40 -30 -20 -10 0 10 20 30 40-40

-30

-20

-10

0

10

20

30

40 Cut 0.1mm

200% 150% 100% 75% 50% 25%

Dis

tanz

a lu

ngo

Z (

mm

)

Distanza lungo X (mm)

Plato-BPS treatment planning algorithm makes some crude approximation ( dependence, no radial dependence)

F()


0 5 10 15 20 25 30 35

5

10

15

20

Ejection spectrumEjection spectrum

RBE enhancement of a RBE enhancement of a 125125I brachytherapy seed with I brachytherapy seed with characteristic X-rays from its constitutive materialscharacteristic X-rays from its constitutive materials

0 5 10 15 20 25 30 35

5

10

15

20

Fluence spectrumFluence spectrum

Ejection spectrumEjection spectrum

Energy (keV)

Per

cent

age

Compton InteractionCompton Interaction Photoelectric effectPhotoelectric effect

R. Taschereau, R. Roy, J. PouliotCentre Hospitalier Universitaire de Québec, Dépt. de radio-oncologie, Canada

Univ. Laval, Dépt. de Physique, CanadaUniv. of California, San Francisco, Dept. of Radiation oncology, USA

Goal: improve the biological effectiveness of titanium encapsulated 125I sources in permanent prostate implants by exploiting X-ray fluorescence

Titanium shell (50 µm)

Silver core (250 µm)

4.5 mm

All the seed configurations modeled and simulated with


Results Results (RBE at 1 cm)(RBE at 1 cm)

Shell = molybdenumUp to 10% improvement

RB

E

Element

Y Zr Nb Mo Ru Rh

39 40 41 42 43 44 45

1.02

1.04

1.06

1.08

1.1

1.12

20 mm

39 40 41 42 43 44 45

1.02

1.04

1.06

1.08

1.1

1.12

20 mm

50 mm

39 40 41 42 43 44 45

1.02

1.04

1.06

1.08

1.1

1.12

20 mm

50 mm

60 mm

39 40 41 42 43 44 45

1.02

1.04

1.06

1.08

1.1

1.12

20 mm

50 mm

60 mm

100 mm150 mm

200 mm300 mm

… up to 300 µmShell experimentsShell experiments

20 µm thick 39 Z 45


Various materials and thicknesses studied with to replace the Ti shell

Optimisation of RBE enhancement

50-60 mm shell Molibdenum


Distance away from seed

RB

E

0 1 2 3 4 5

1

1.02

1.04

1.06

1.08

M200

0 1 2 3 4 5

1

1.02

1.04

1.06

1.08

Mo- Y

M200

-- healthy tissues++ tumors

Possible to improve RBE

Applications- Prostate

- Ocular melanoma

- Coronary brachytherapy

Results of the studyResults of the study


Enhanced RBE combined with relatively long half-life of iodine could mean higher cell kill

(where a highly localized dose distribution is desired)


M.C. Lopes 1, L. Peralta 2, P. Rodrigues 2, A. Trindade 2

1 IPOFG-CROC Coimbra Oncological Regional Center - 2 LIP - Lisbon


Validation of phase-space distributions from a Siemens KD2 linear accelerator at 6 MV photon mode

Central-Axis depth dose curve for a 10x10 cm2 field size, compared with

experimental data (ionization chamber)

identified as experimental problemM. C. Lopes 1, L. Peralta 2, P. Rodrigues 2, A. Trindade 2

1 IPOFG-CROC Coimbra Oncological Regional Center

2 LIP - Lisbon

testing testing and validationand validation


Profile curves at 9.8 cm depth PLATO overestimate the dose at ~ 5% level

Central-Axis depth dose

CT-simulation with a Rando phantomExperimental data obtained with TLD LiF dosimeter

Deviation at –6 cm identified as an experimental problem

CT images used to define the geometry:

a thorax slice from a Rando anthropomorphic phantom

Comparison with commercial treatment planning systemsComparison with commercial treatment planning systems

M. C. Lopes 1, L. Peralta 2, P. Rodrigues 2, A. Trindade 2



M. C. Lopes1, L. Peralta2, P. Rodrigues2, A. Trindade2


Head and neck with two opposed beams for a 5x5 and 10x10 field size

A more complex set-upA more complex set-up

An off-axis depth dose taken at one of the slices near the isocenter

PLATO fails on the air cavities and bone structures and cannot predict accurately the dose to tissue that is surrounded by air

Deviations are up to 25-30%

Beam planeSkull bone

Tumor


Many other Many other applications and applications and

new projectsnew projects

Pixel ionisation chamber

Relative dose in water

CT interface + fast/full simulation

Use GEANT4 to obtain digitally reconstructed radiographs (DRRs), including full scatter simulation

This represents a great improvement over approaches based on ray-casting

Hadrontherapy studies In vivo dosimetry (mammography, colonscopy),

Superposition and fusion of anatomic and functional images PET Intra-operatory radiotherapy etc.

Also theoretical developments to improve the evaluated data libraries


-- DNADNA

Relevance for space: astronaut and airline pilot radiation hazards, biological experiments

Applications in radiotherapy, radiobiology...

Study of radiation damage at the cellular and DNA level in the space radiation environment(and other applications, not only in the space domain)

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

Prototyping

Multi-disciplinary Collaboration of astrophysicists/space scientists particle physicists medical physicists computer scientists biologists physicians

5.3 MeV particle in a cylindrical volume.

The inner cylinder has a radius of 50 nm.

Maria Grazia Pia, INFN Genova - Como 2001Cou

rtes

y A

. Bra

hme

(KI)

It is a complex field- ongoing active research

Complexity increased by the multi-disciplinary nature of the project

- no one masters all the scientific components (biology, chemistry, physics etc.)

GEANT4-DNA

Simulation of interactions of radiation with biological systems at the cellular and DNA level

User Requirements Document Status: Delivered to ESA on 22 February 2001

Version: 1.3 Project: Geant4-DNA Reference: DNA-URD-V1.03 Created: 28 December 2000 Last modified: 21 February 2001

Prepared by: Maria Grazia Pia (INFN Genova) Stéphane Chauvie (Univ. of Torino and INFN Torino and AIRCC) Gabriele Cosmo (CERN) José Maria Fernandez Varea (Univ. of Barcelona) Franca Foppiano (IST Genova - Istituto Nazionale per la Ricerca sul Cancro) Petteri Nieminen (ESA/ESTEC) Ada Solano (Univ. of Torino and INFN Torino)

On behalf of the Geant4-DNA Collaboration

A rigorous approach to the collection of the requirements is essential

A challenge for problem domain analysis and design!

User RequirementsUser Requirements


What benefits for HEP?What benefits for HEP?

User requirementsUser requirements

TestingTesting

Feedback from usage Feedback from usage in diverse environmentsin diverse environments

Discipline of strict Discipline of strict protocolsprotocols

Technology transfer is a helpful argument with funding agencies for supporting HEP

Identification of requirements of common interest Contribution to sharper requirement specification …

Substantial contributions from medical groups

Improves the quality and robustness of the code

Contribution to software process improvement Incentive to better quality assurance methods Profit of other fields’ experience in software process for

reliable products


The www was born from HEP…

Geant4 in every hospital?


in Savonain Savona

A project in progress for the simulation with of brachytherapy 125I sources for prostate cancer therapy– Calibration– Precise dose distribution installed on the PC of the Medical Physics Service of the Hospital

Brachytherapy at the Hospital of SavonaSavona


Meditations…Meditations…

HEP computing has a potential for technology transfer - not only the WWW…

- not only Geant4…

The role of HEP: expertise, but also reference- Physics and software engineering expertise

- Reference to many small groups and diverse activities

Technology transfer: collaboration rather than colonisation- Valuable contributions from the medical domain (requirements, testing,

rigorous methodologies…)

- New resources into projects of common interest

- Plenty of valuable applications and results


Thanks!Thanks!

ESA/ESTEC (R. Nartallo, P. Nieminen)

INFN Cosenza (E. Lamanna)

INFN Torino (S. Chauvie, R. Gotta, F. Marchetto, V. Rolando, A. Solano)

IST (S. Agostinelli, R. Corvo, F. Foppiano, S. Garelli, G. Sanguineti, M. Tropeano)

LIP (P. Rodrigues, A. Trindade)

Univ. Laval / UCSF (R. Taschereau)

PSI (N. Crompton, P. Juelke)

Savona Hospital (G. Ghiso, R. Martinelli)

Geant4 medical users (impossible to mention all…)

Geant4 Collaboration

CERN (G. Cosmo, S. Giani, J. Knobloch)

Documents

Maria Grazia Pia, INFN Genova - Como 2001 From HEP computing to bio-medical research and vice versa Simulation software: applications and results in the