Maria Grazia Pia, INFN Genova Particle Physics Particle Physics Software Software and the and the Fight against Cancer Fight against Cancer Maria Grazia Pia INFN Genova Seminar at DESY 9 February 2004 http://www.ge.infn.it/geant4/talks S. Guatelli (INFN and Univ. Genova) S. Agostinelli, F. Foppiano, S. Garelli (IST Genova) L. Archambault, L. Beaulieu, J.-F. Carrier, V.-H. Tremblay (Univ. Laval) M.C. Lopes, L. Peralta, P. Rodrigues, A. Trindade (LIP Lisbon) G. Ghiso (S. Paolo Hospital, Savona) Including contributions from:
Transcript
Maria Grazia Pia, INFN Genova
Particle Physics Software Particle Physics Software and the and the
Fight against CancerFight against Cancer
Maria Grazia PiaINFN Genova
Seminar at DESY 9 February 2004
http://www.ge.infn.it/geant4/talks
S. Guatelli (INFN and Univ. Genova)S. Agostinelli, F. Foppiano, S. Garelli (IST Genova)
L. Archambault, L. Beaulieu, J.-F. Carrier, V.-H. Tremblay (Univ. Laval)M.C. Lopes, L. Peralta, P. Rodrigues, A. Trindade (LIP Lisbon)
G. Ghiso (S. Paolo Hospital, Savona)
Including contributions from:
Maria Grazia Pia, INFN Genova
Technology transfer
Particle physics software Particle physics software aids space and medicineaids space and medicine
June 2002
http://www.cerncourier.com
“Geant4 is a showcase example of technology transfer from
particle physics to other fields such as space and medical science”
Maria Grazia Pia, INFN Genova
The goal of radiotherapyThe goal of radiotherapy
Delivering the required therapeutic dose to the tumor area with high precision,
while preserving the surrounding healthy tissue
Dosimetry system precision accurate model of the real configuration (from CT)
speed adequate for clinical use user-friendly interface for hospital usage
Calculate the dose released to the patient by the
radiotherapy system
Accurate dosimetry is at the basis of radiotherapy treatment planning
Maria Grazia Pia, INFN Genova
The realityThe reality
Treatment planning is performed by means of commercial software
The software calculates the dose distribution delivered to the patient in a given source configuration
Open issues
PrecisionPrecision CostCost
Commercial systems are based on approximated analytical methods,approximated analytical methods, because of speed constraints
Approximation in geometry modelinggeometry modeling
Approximation in material modeling material modeling
Each treatment planning software is specific to one techniquespecific to one technique and one type of sourceone type of source
Treatment planning software is expensiveexpensive
Maria Grazia Pia, INFN Genova
Commercial factorsCommercial factorsCommercial treatment planning systems are governed by commercial rules (as any other commercial product...)
i.e., they are produced and marketed by a company only if the investment for development is profitable
No commercial treatment planning systems are available for non-conventional radiotherapy techniques such as hadrontherapyhadrontherapy
or for niche applications such as superficial brachytherapysuperficial brachytherapy
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-20 -15 -10 -5 0 5 10 15 20
Distance from the centre (mm)
Sig
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Film X
Microcubes X
Treatment planning systems for hadrontherapy are quite primitive
not commercially convenient so far
Maria Grazia Pia, INFN Genova
Monte Carlo methods in radiotherapyMonte Carlo methods in radiotherapy
Monte Carlo methods have been explored for years as a tool for precise dosimetry, in alternative to analytical methods
de facto,
Monte Carlo simulation is not used in clinical practice
(only side studies)
The limiting factor is the speedspeedOther limitations: reliable? for “software specialists only”, not user-friendly for general practice requires ad hoc modeling
Maria Grazia Pia, INFN Genova
The challenge
Maria Grazia Pia, INFN Genova
Develop a Develop a general purposegeneral purpose
precise precise dosimetric system
with the capability of
realistic geometryrealistic geometryand material modelingand material modeling
interface to CT imagesinterface to CT images
with a user-friendly interfaceuser-friendly interface
atat low costlow cost
adequate adequate speedspeed for clinical usage for clinical usageperforming atperforming at
Maria Grazia Pia, INFN Genova
A real life case A dosimetric system for A dosimetric system for
brachytherapybrachytherapy(but all the developments and applications
presented in this talk are general)
How particle physics software can contribute to
oncological radiotherapy
How particle physics software can contribute to
oncological radiotherapy
Maria Grazia Pia, INFN Genova
Activity initiated at IST Genova, Natl. Inst. for Cancer Research (F. Foppiano et al.)
– hosted at San Martino Hospital in Genova (the largest hospital in Europe)
Collaboration with San Paolo Hospital, Savona (G. Ghiso et al.)– a small hospital in a small town
Major work by Susanna Guatelli (Univ. and INFN Genova)
MSc. Thesis, Physics Dept., University of Genova, 2002http://www.ge.infn.it/geant4/tesi/
The prototypeThe prototype
Maria Grazia Pia, INFN Genova
Brachytherapy is a medical therapy used for cancer treatment
Radioactive sources are used to deposit therapeutic doses near tumors, while preserving surrounding healthy tissues TechniquesTechniques
Commercial software for brachytherapyCommercial software for brachytherapy
Various commercial software products for treatment planning – eg. Variseed V 7, Plato BPS, Prowes
No commercial software available for superficial brachytherapy with Leipzig applicators
PrecisionPrecision
CostCost
Based on approximated analytical methods,approximated analytical methods, because of speed constraints Approximation in source anisotropysource anisotropy Uniform materialUniform material: water
Each software is specific to one techniquespecific to one technique and one type of sourceone type of source Treatment planning software is expensiveexpensive (~ hundreds K $/euro)
Accurate model of the real experimental set-upAccurate model of the
real experimental set-up
Easy configuration for hospital usage
Easy configuration for hospital usage
SpeedSpeed
Calculation of 3-D dose distribution3-D dose distribution in tissueDetermination of isodose isodose curves
Based on Monte CarloMonte Carlo methodsAccurate description of physicsphysics interactionsExperimental validationvalidation of physics involved
Realistic description of geometrygeometry and tissuetissuePossibility to interface to CT images
Simple user interface + Graphic visualisation Elaboration of dose distributionsdose distributions and isodosesisodoses
ParallelisationParallelisationAccess to distributed computing resourcesdistributed computing resources
Other requirementsOther requirementsTransparentTransparentOpen to extension extension and new functionalityPublicly accessiblePublicly accessible
RequirementsRequirementsRequirementsRequirements
Maria Grazia Pia, INFN Genova
The software processThe software process
The process follows an iterative and incremental
model
The project is characterized by a
rigorous software processrigorous software process
Process based on the Unified Process, especially tailored to the specific context of the project
RUP used as a practical guidance to the process
Maria Grazia Pia, INFN Genova
PrecisionPrecisionPrecisionPrecision
Based on Monte Carlo methodsMonte Carlo methods
Extension of electromagnetic interactions down to low energies (< 1 keV)
Microscopic validation of the physics modelsMicroscopic validation of the physics modelsComparison Comparison with experimental data experimental data
specific to the brachytherapic practice
Accurate description of physicsphysics interactions
Experimental validationvalidation of physics involved
Maria Grazia Pia, INFN Genova
The foundation
What characterizes Geant4What characterizes Geant4
The fundamental concepts, upon which all the rest is built
Maria Grazia Pia, INFN Genova
PhysicsPhysicsPhysicsPhysicsFrom 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.”
Maria Grazia Pia, INFN Genova
Domain decomposition
hierarchical structure of
sub-domains
Geant4 architecture
Uni-directional flow of
dependencies
Interface to external products w/o dependencies
Software EngineeringSoftware Engineeringplays a fundamental role in
Geant4User Requirements
• formally collected• systematically updated• PSS-05 standard
Software Process• spiral iterative approach• regular assessments and improvements (SPI process)• 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
• openness to extension and evolution• contribute to the transparency of physics• interface to external software without dependencies
Use of Standards • de jure and de facto
Maria Grazia Pia, INFN Genova
The functionality
What Geant4 can doWhat Geant4 can do
Maria Grazia Pia, INFN Genova
Code and documentation publicly distributed from web
1st production release: end 1998– 2 new releases/year since then
Developed and maintained by an international collaboration of physicists and computer scientists
Run, Event and Track management PDG-compliant Particle management Geometry and Materials Tracking Detector response User Interface Visualisation Persistency Physics Processes
Maria Grazia Pia, INFN Genova
Detailed detector description and efficient navigation
High energy extensionsHigh energy extensions– needed for LHC experiments, cosmic ray experiments…
Low energy extensionsLow energy extensions– fundamental for space and medical applications, dark matter
and experiments, antimatter spectroscopy etc. Alternative models for the same processAlternative models for the same process
electrons and positrons, X-ray and optical photons
muons charged hadrons
ions
Data-driven, Parameterised and Theoretical modelsData-driven, Parameterised and Theoretical models– the most complete hadronic simulation kit on the market– alternative and complementary models
Cross section data sets: Cross section data sets: transparent and interchangeable
Final state calculation: Final state calculation: models by particle, energy, material
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
Air
Bone
In some tumours sites (ex: larynx T2/T3-stage) a 5% underdosage will decrease local tumour
control probability from ~75% to ~50%
Maria Grazia Pia, INFN Genova
Physics
Physics models in Geant4 relevant Physics models in Geant4 relevant
to medical applicationsto medical applications
Maria Grazia Pia, INFN Genova
Low Energy Electromagnetic PhysicsLow Energy Electromagnetic Physics
A set of processes extending the coverage of electromagnetic A set of processes extending the coverage of electromagnetic interactions in Geant4 down to “interactions in Geant4 down to “low”low” energy energy
– 250 eV (in principle even below this limit) for electrons and photons– down to approximately the ionisation potential of the interacting material for
hadrons and ions
Processes based on detailed modelsProcesses based on detailed models– shell structure of the atom– precise angular distributions
Specialised models depending on particle typeSpecialised models depending on particle type– data-driven models based on the Livermore Libraries for e- and photons– analytical models for e+, e- and photons (reengineering of Penelope into Geant4)– parameterised models for hadrons and ions (Ziegler 1977/1985/2000, ICRU49)– original model for negative hadrons
Maria Grazia Pia, INFN Genova
Barkas effect (charge dependence)models for negative hadrons
e,down to 250 eV
EGS4, ITS to 1 keVGeant3 to 10 keV
Hadron and ion models based on Ziegler and ICRU data and parameterisations
Based on EPDL97, EEDL and EADL evaluated data libraries
Bragg peak
shell effects
antiprotons
protonsions
Fe lines
GaAs lines
Atomic relaxation Fluorescence
Auger effect
Based on Penelope analytical models
Maria Grazia Pia, INFN Genova
Globalisation
Sharing requirements and functionality
across diverse fields
scientific…
Maria Grazia Pia, INFN Genova Courtesy ESA Space Environment & Effects Analysis Section
X-Ray Surveys of Planets, Asteroids and Moons
Induced X-ray line emission:indicator of target composition
(~100 m surface layer)
Cosmic rays,jovian electrons
Solar X-rays, e, p
Courtesy SOHO EIT
Geant3.21
ITS3.0, EGS4
Geant4
C, N, O line emissions included
low energy e/ extensionswere triggered by astrophysics requirements
Maria Grazia Pia, INFN Genova
……the first user applicationthe first user application
R. Taschereau, R. Roy, J. PouliotCentre Hospitalier Universitaire de Quebec, Dept. de radio-oncologie, CanadaUniv. Laval, Dept. de Physique, CanadaUniv. of California, San Francisco, Dept. of Radiation Oncology, USA
Distance away from seed
RB
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Mo- Y
M200
-- healthy tissues++ tumors
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
Maria Grazia Pia, INFN Genova
low energy p/ion extensions low energy p/ion extensions
were triggered by hadrontherapy requirements
CATANA, INFN-LNS
Maria Grazia Pia, INFN Genova
...effects of low energy protons on X-ray telescopes...effects of low energy protons on X-ray telescopes
“Analysis of ACIS calibration source data from the last 5 days has shown an unexplained
degradation in the energy resolution of the front-side illuminated CCD chips of ACIS. The degradation is
evident in data starting from 5 days ago and shows a change in the FWHM from approx 130 eV to 500 eV.”
Operations CXO Status ReportFriday 9/10/99 10:00am EST EPIC image of the two flaring Castor
components and the brighter YY Gem
Courtesy of R. Nartallo, ESA
XMM-Newton
Maria Grazia Pia, INFN Genova
...back to ...back to HEPHEP
Similar requirements on low energy physics from underground experiments
LHC for precision detector simulation?
Gran Sasso Laboratory
Credit: O. Cremonesi, INFN Milano
Courtesy H. Araujo and A. Howard, IC London
ZEPLIN III
Maria Grazia Pia, INFN Genova
Validation
Microscopic validation:
verification of Geant4 physicsverification of Geant4 physics
Dosimetric validation: in the experimental contextin the experimental context
Maria Grazia Pia, INFN Genova
proton straggling
ions
e-, Sandia database
Al
NISTGeant4-LowEGeant4-Standard
Stopping power
Microscopic validationMicroscopic validation
many more
validation results
available!
2N-L=13.1 – =20 - p=0.87
NISTGeant4-LowEGeant4-Standard
Photon attenuation coefficient
Al
2N-S=23.2 – =15 - p=0.08
Maria Grazia Pia, INFN Genova
Dosimetric validationDosimetric validation
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0,4
0,6
0,8
1,0
1,2 Simulazione Nucletron Misure
Dose %
Distanza lungo Z (mm)Distance along Z (mm)
SimulationNucletronData
F. Foppiano et al., IST Genova
Comparison to
manufacturer data, protocol data,
original experimental data
experimental mesurements
G. Ghiso, S. Guatelli S. Paolo Hospital Savona
Ir-192 I-125
Maria Grazia Pia, INFN Genova
General purpose systemGeneral purpose systemGeneral purpose systemGeneral purpose system
Object Oriented technologySoftware system designed in terms of Abstract Interfaces
Abstract Factory design patternSource spectrum and geometry transparently interchangeableSource spectrum and geometry transparently interchangeable
For any brachytherapy technique
For any source type
Maria Grazia Pia, INFN Genova
Flexibility of modelingFlexibility of modeling
CT DICOM interface
through Geant4 parameterised volumesGeant4 parameterised volumes parameterisation function: materialparameterisation function: material
Abstract Factory
Configuration of
any brachytherapy technique any brachytherapy technique
any source type any source type
through an Abstract FactoryAbstract Factory to define geometry, primary geometry, primary spectrumspectrum
Phantom
various materialsvarious materials water, soft tissue, bone, muscle etc.
General purpose software system for brachytherapy
No commercial general software exists!
Maria Grazia Pia, INFN Genova
Realistic model Realistic model of the experimental set-upof the experimental set-up
Realistic model Realistic model of the experimental set-upof the experimental set-up
Spectrum (192IrIr, 125II)Geometry
Phantom with realistic material modelPhantom with realistic material modelPossibility to interface the system to CT imagesPossibility to interface the system to CT images
Radioactive source
Patient
Maria Grazia Pia, INFN Genova
Modeling the source geometry
Modeling the source geometry
Precise geometry and material model of any type of source
prototype for an intermediate layer between applications and the GRID
Parallel cluster processingParallel cluster processing– make fine tuning and customisation easy– transparently using GRID technology– application independentapplication independent
Hide complex details of
underlying technology
Developed by J. Moscicki, CERN
http://cern.ch/DIANE
Maria Grazia Pia, INFN Genova
DIANE architectureDIANE architecture
Master-Worker modelMaster-Worker modelParallel execution of independent tasksVery typical in many scientific applicationsUsually applied in local clusters
R&D in progress forR&D in progress forLarge Scale Master-Large Scale Master-Worker ComputingWorker Computing
Maria Grazia Pia, INFN Genova
Running in a distributed environment
Running in a distributed environment
Not affecting the original code of application– standalone and distributed case is the same codesame code
Good separation of the subsystems– the application does not need to know that it runs in distributed environment– the distributed framework (DIANE) does not need to care about what
actions an application performs internally
The application developer is shielded from the complexity of underlying technology via DIANE
Maria Grazia Pia, INFN Genova
Parallel mode: local clusterParallel mode: local cluster
Same application code as running on a sequential machine or on a dedicated cluster
– completely transparent to the user
A hospital is not required to own and maintain extensive computing resources to exploit the scientific advantages of Monte Carlo simulation for radiotherapy
Any hospital
– even small ones, or in less wealthy countries, that cannot even small ones, or in less wealthy countries, that cannot afford expensive commercial software systemsafford expensive commercial software systems –
may have access to advanced software technologies and tools for radiotherapy
Beware: R&D prototype!Beware: R&D prototype!
Maria Grazia Pia, INFN Genova
Other requirementsOther requirementsOther requirementsOther requirements
Transparency
OO technology: plug-ins for other techniquesTreatment head
Beam line for hadrontherapy...
Application code released with Geant4Application code released with Geant4Based on open source code Based on open source code (Geant4, AIDA etc.)(Geant4, AIDA etc.)
Openness to extension and new functionality
Publicly accessible
Design and code publicly distributedDesign and code publicly distributedPhysics and models exposed through OO designPhysics and models exposed through OO design
Maria Grazia Pia, INFN Genova
TransparencyTransparencyTransparencyTransparencyMedical physics does not only require fast simulation and fancy analysis…
Transparency of physics
Advanced functionalityin geometry, physics, visualisation etc.
Extensibility to accomodate new user requirements
Adoption of standards wherever available
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 HEP softwareis relevant to the
bio-medical community?
A rigorous software process
Specific facilities controlled by a friendly UI
Maria Grazia Pia, INFN Genova
Extension and evolutionExtension and evolution
General dosimetry system for radiotherapyGeneral dosimetry system for radiotherapy extensible to other techniques
plug-ins for external beamsplug-ins for external beams
((factories for beam, geometry, physics...)
Plug-ins in progress
System extensible to any source configuration without changing the existing code
treatment headtreatment head hadrontherapyhadrontherapy ......
Maria Grazia Pia, INFN Genova
Meditations…Meditations…HEP computing has a potential for technology transfer
– not only the WWW…– also Geant4, analysis tools, the GRID…
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– Avoid the “colonial” attitude
We would benefit from a greater investment in outreach– it pays back, in terms of political and scientific return
Maria Grazia Pia, INFN Genova
Thanks!Thanks!
S. Guatelli (INFN and Univ. Genova)
S. Agostinelli, F. Foppiano, S. Garelli (IST Genova)
G. Cosmo (CERN, Geant4),
L. Moneta, I. Papadopoulos, A. Pfeiffer, M. Sang (CERN, Anaphe)
J. Moscicki (CERN, DIANE)
J. Knobloch (CERN/IT)
G. Ghiso, R. Martinelli (S. Paolo Hospital, Savona)
S. Chauvie (INFN Torino and Cuneo Hospital)
G.A.P. Cirrone, G. Cuttone (INFN LNS, CATANA project)
M.C. Lopes, L. Peralta, P. Rodrigues, A. Trindade (LIP Lisbon)
L. Archambault, J.F. Carrier, L. Beaulieu, V.H. Tremblay (Univ. Laval)
Geant4 has fostered a collaborative aggregation of contributions from many groups all over the world
