Maria Grazia Pia, INFN Genova - Como 2001 From HEP computing to bio-medical research and vice versa...
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Transcript of Maria Grazia Pia, INFN Genova - Como 2001 From HEP computing to bio-medical research and vice versa...
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
Maria Grazia Pia, INFN Genova - Como 2001
Globalisation
Sharing requirements and functionalities
across diverse fields
Maria Grazia Pia, INFN Genova - Como 2001
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)
Maria Grazia Pia, INFN Genova - Como 2001
LowE Hadrons and ionsLowE Hadrons and ions
OOAD… OOAD…
Maria Grazia Pia, INFN Genova - Como 2001
……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
Maria Grazia Pia, INFN Genova - Como 2001
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
Maria Grazia Pia, INFN Genova - Como 2001
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
Maria Grazia Pia, INFN Genova - Como 2001
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
Maria Grazia Pia, INFN Genova - Como 2001
……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
Maria Grazia Pia, INFN Genova - Como 2001
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,
Maria Grazia Pia, INFN Genova - Como 2001
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
Maria Grazia Pia, INFN Genova - Como 2001
……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
Maria Grazia Pia, INFN Genova - Como 2001
……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
Maria Grazia Pia, INFN Genova - Como 2001
A lesson to learn
What may look far from the scope of HEP today,
may be required as an essential functionality
tomorrow
Open mind…
Maria Grazia Pia, INFN Genova - Como 2001
What can HEP propose?
ToolsMethodologies
Maria Grazia Pia, INFN Genova - Como 2001
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
Maria Grazia Pia, INFN Genova - Como 2001
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
Maria Grazia Pia, INFN Genova - Como 2001
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
Maria Grazia Pia, INFN Genova - Como 2001
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
Maria Grazia Pia, INFN Genova - Como 2001
Applications
Verification of conventional radiotherapy treatment
planning (as required by protocols)
Investigation of innovative methods in radiotherapy
Radiodiagnostics
Maria Grazia Pia, INFN Genova - Como 2001
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
Maria Grazia Pia, INFN Genova - Como 2001
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
Maria Grazia Pia, INFN Genova - Como 2001
Source anisotropy
Especially for uterus, vagina and lung cancer
Treatment planning systems include algorithms to account for source anisotropy
Endocavitary Endocavitary brachytherapybrachytherapy
Maria Grazia Pia, INFN Genova - Como 2001
-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
Maria Grazia Pia, INFN Genova - Como 2001
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()
Maria Grazia Pia, INFN Genova - Como 2001
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
Maria Grazia Pia, INFN Genova - Como 2001
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
R. Taschereau, R. Roy, J. Pouliot
Various materials and thicknesses studied with to replace the Ti shell
Optimisation of RBE enhancement
50-60 mm shell Molibdenum
Maria Grazia Pia, INFN Genova - Como 2001
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
R. Taschereau, R. Roy, J. Pouliot
Enhanced RBE combined with relatively long half-life of iodine could mean higher cell kill
(where a highly localized dose distribution is desired)
Maria Grazia Pia, INFN Genova - Como 2001
M.C. Lopes 1, L. Peralta 2, P. Rodrigues 2, A. Trindade 2
1 IPOFG-CROC Coimbra Oncological Regional Center - 2 LIP - Lisbon
Maria Grazia Pia, INFN Genova - Como 2001
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
Maria Grazia Pia, INFN Genova - Como 2001
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
1 IPOFG-CROC Coimbra Oncological Regional Center - 2 LIP - Lisbon
Maria Grazia Pia, INFN Genova - Como 2001
M. C. Lopes1, L. Peralta2, P. Rodrigues2, A. Trindade2
1 IPOFG-CROC Coimbra Oncological Regional Center - 2 LIP - Lisbon
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
Maria Grazia Pia, INFN Genova - Como 2001
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
Maria Grazia Pia, INFN Genova - Como 2001
-- 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
Maria Grazia Pia, INFN Genova - Como 2001
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
Maria Grazia Pia, INFN Genova - Como 2001
The www was born from HEP…
Geant4 in every hospital?
Maria Grazia Pia, INFN Genova - Como 2001
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
Maria Grazia Pia, INFN Genova - Como 2001
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
Maria Grazia Pia, INFN Genova - Como 2001
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)