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

2. Maria Grazia Pia, INFN Genova - Como 2001 Globalisation Sharing requirements and functionalities across diverse fields

3. Maria Grazia Pia, INFN Genova - Como 2001 Requirements for LowE p in UR 2.1The 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

4. Maria Grazia Pia, INFN Genova - Como 2001 LowE Hadrons and ions OOAD…

5. Maria Grazia Pia, INFN Genova - Como 2001 …and validation Courtesy of R. Gotta, Thesis INFN-Torino medical physics group Geant4 LowE Working Group Experimental data: Bragg peak data O simulation Test set-up at PSI

6. Maria Grazia Pia, INFN Genova - Como 2001 What could be the source of 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

7. Maria Grazia Pia, INFN Genova - Como 2001 CCD displacement damage: front vs. back-illuminated. 30  m 2  m 30  m 2  m 30  m Si  ~1.5 MeV protons Active layer Passive layer “Electron deflector” EPIC RGS ESA Space Environment & Effects Analysis Section Courtesy of Low-E (~100 keV to few MeV), low-angle (~0°-5°) proton scattering

8. Maria Grazia Pia, INFN Genova - Como 2001 What happened next? XMM was launched on 10 December 1999 from Kourou EPIC image of the two flaring Castor components and the brighter YY Gem Courtesy of

9. Maria Grazia Pia, INFN Genova - Como 2001 …and the other way round

10. Maria Grazia Pia, INFN Genova - Como 2001 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 Geant3.21 ITS3.0, EGS4 Geant4 Solar X-rays, e, p Courtesy SOHO EIT C, N, O line emissions included Low energy e,  extensions …were triggered by astrophysics requirements

11. 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 GeV Low Energy Processes: e, 

12. Maria Grazia Pia, INFN Genova - Como 2001 Photon attenuation: vs. NIST data waterFe Pb 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

13. Maria Grazia Pia, INFN Genova - Como 2001 …the first user application 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 125 I sources in permanent prostate implants

14. Maria Grazia Pia, INFN Genova - Como 2001 …and 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

15. 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…

16. Maria Grazia Pia, INFN Genova - Como 2001 What can HEP propose? Tools Methodologies

17. 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

18. Maria Grazia Pia, INFN Genova - Como 2001 Physics requirements 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 ions Geant4 Geant3 data And much more: fluorescence radioactive decay hadronic models etc… And many relevant functionalities in other domains too, not only physics! New multiple scattering model

19. Maria Grazia Pia, INFN Genova - Como 2001 Guidelines for physics From the Minutes of LCB (LHCC Computing Board) meeting on 21 October, 1997: Physics open to evolution 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: fundamental for “sensitive”applications, such as medical ones

20. 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

21. 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

22. Maria Grazia Pia, INFN Genova - Como 2001 The IST group follows the direction of Basic Dosimetry on Radiotherapy with Brachytherapy Source of the Italian Association of Biomedical Physics (AIFB) Brachytherapy 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 Protocols require testing the treatment planning systems

23. Maria Grazia Pia, INFN Genova - Como 2001 Distance along Z (mm) Simulation Nucletron Data Transverse distance (mm) Depth (mm) Experimental validation Leipzig applicators Courtesy F. Foppiano, M. Tropeano Brachytherapy Brachytherapy at the Natl. Inst. for Cancer Research (IST-Genova) Superficial brachytherapy

24. 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 brachytherapy

25. Maria Grazia Pia, INFN Genova - Como 2001 Distance along X (mm) Simulation Plato Data Distance along Z (mm) Simulation Plato Longitudinal 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 source Comparison with experimental data  validation of the software Role of the simulation: Courtesy F. Foppiano, M. Tropeano precise evaluation of the effects of source anisotropy in the dose

26. Maria Grazia Pia, INFN Genova - Como 2001 Courtesy of S. Agostinelli, R. Corvo, F. Foppiano, S. Garelli, G. Sanguineti, M. Tropeano, IST Genova Source anisotropy Plato treatment planning Plato-BPS treatment planning algorithm makes some crude approximation (  dependence, no radial dependence) F(  )

27. Maria Grazia Pia, INFN Genova - Como 2001 Ejection spectrum RBE enhancement of a 125 I brachytherapy seed with characteristic X-rays from its constitutive materials Fluence spectrum Ejection spectrum Energy (keV) Percentage Compton Interaction Photoelectric effect R. Taschereau, R. Roy, J. Pouliot Centre Hospitalier Universitaire de Québec, Dépt. de radio-oncologie, Canada Univ. Laval, Dépt. de Physique, Canada Univ. of California, San Francisco, Dept. of Radiation oncology, USA Goal: improve the biological effectiveness of titanium encapsulated 125 I 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

28. Maria Grazia Pia, INFN Genova - Como 2001 Results (RBE at 1 cm) Shell = molybdenum Up to 10% improvement RBE Element YZrNbMoRuRh … up to 300 µm Shell 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

29. Maria Grazia Pia, INFN Genova - Como 2001 Distance away from seed RBE -- healthy tissues++ tumors Possible to improve RBE Applications -Prostate -Ocular melanoma -Coronary brachytherapy Results 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)

30. 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

31. 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 problem M. C. Lopes 1, L. Peralta 2, P. Rodrigues 2, A. Trindade 2 1 IPOFG-CROC Coimbra Oncological Regional Center 2 LIP - Lisbon testing and validation testing and validation

32. 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 phantom Experimental 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 systems M. C. Lopes 1, L. Peralta 2, P. Rodrigues 2, A. Trindade 2 1 IPOFG-CROC Coimbra Oncological Regional Center - 2 LIP - Lisbon

33. 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 Head and neck with two opposed beams for a 5x5 and 10x10 field size A 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 plane Skull bone Tumor

34. Maria Grazia Pia, INFN Genova - Como 2001 Many other applications and new 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

35. Maria Grazia Pia, INFN Genova - Como 2001 - DNA - DNA 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 n astrophysicists/space scientists n particle physicists n medical physicists n computer scientists n biologists n physicians 5.3 MeV  particle in a cylindrical volume. The inner cylinder has a radius of 50 nm.

36. Maria Grazia Pia, INFN Genova - Como 2001 Courtesy A. Brahme (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.) A rigorous approach to the collection of the requirements is essential A challenge for problem domain analysis and design! User Requirements

37. Maria Grazia Pia, INFN Genova - Como 2001 What benefits for HEP? User requirements Testing Feedback from usage in diverse environments Discipline of strict protocols 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

38. Maria Grazia Pia, INFN Genova - Como 2001 The www was born from HEP… Geant4 in every hospital?

39. Maria Grazia Pia, INFN Genova - Como 2001 in Savona in Savona A project in progress for the simulation with of brachytherapy 125 I 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 Savona Savona

40. Maria Grazia Pia, INFN Genova - Como 2001 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

41. Maria Grazia Pia, INFN Genova - Como 2001 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)