Mantra Mooloolaba-Beach, Queensland Australia, February 6th-11th 2018 mmnditro2018.com cmrp@uow.edu.au GOLD SPONSORS SILVER SPONSORS Mantra Mooloolaba-Beach, Queensland Australia, February 6th-8th 2018 mmnditro2018.com cmrp@uow.edu.au Welcome from the Chair Continuing our series of biennial meetings, the Micro-Mini & Nano Dosimetry (MMND) workshop (6th - 8th February) brings together both international and Australian radiation oncologists, medical physicists, radiation scientists and nanomedicine experts to discuss advancement in radiation oncology modalities and radiation dosimetry technologies for quality assurance in radiation therapy, radiobiological optimisation of treatments, and oth- er relevant technologies, to further improve clinical outcomes of radiation therapy. For the first time in the history of the MMND workshop series, we will be holding a special "Brachytherapy Day". This will be led by Dr Michael Zelefsky, Memorial Sloan Kettering Cancer Center (MSKCC), New York. Distinguished Professor Anatoly Rozenfeld, PhD MMND—International Faculty Professor Reinhard Schulte, MD Reinhard Schulte, MD, is Professor of Radiation Medicine in the School of Medicine of Loma Linda University, and works as Translational Researcher on proton and ion therapy related technology and clinical developments in the James M. Slater Pro- ton Treatment and Research Center, Department of Radiation Medicine, Loma Linda University Medical Center. He received his graduate degree in Physics (Diploma) from Dortmund University, Germany and his Doctorate in Medicine (Dr. med., summa cum laude) from the University of Cologne, Germany. He is Principal Investigator on an NIH-funded project to develop proton CT and participates in two large European Research Consortia related to proton therapy research. Dr. Schulte also has over 25 years of experience in clinical proton therapy and is licensed physician and board certified in radiation oncology and radiology in the United States and Germany. Professor Vladimir Feygelman, PhD Vladimir M. Feygelman graduated from the Department of Physics at Rostov State University in the former U.S.S.R in 1982 with a degree in Laser Physics. In 1985 he was awarded a PhD in Physical Chemistry at the same university. Since 1990 Dr. Feygel- man is involved in Medical Physics, first as a Post Doc at the University of Florida (Gainesville), and then as a clinical radiothera- py physicist in Canada and USA. In 2006 he joined the faculty of Moffitt Cancer Center. Currently he is a Senior Faculty Mem- ber at Moffitt and Professor at USF Department of Oncologic Sciences. Dr. Feygelman divides his time between clinical duties, research, and teaching physics PhD students and medical residents. As a senior physicist, he is responsible for implementation of all major technological developments at the Department of Radiation Oncology. His research interests are primarily focused on quality assurance of complex advanced treatments. Dr. Feygelman was a member of the AAPM Task Group 244 on commis- sioning of dose calculations. He was the principal writer of the IMRT/VMAT section. Currently he serves as a Co-Chair of the AAPM working group on reference dose specification in treatment planning systems. Dr. Feygelman is an author of over 50 peer-reviewed papers on Medical Physics and was an invited speaker at various national and international meetings such as AAPM, ESTRO, and IEEE. MMND—International Faculty Professor Wolfgang Tomé, PhD Professor Tomé works at Montefiore Medical Center and the Albert Einstein College of Medicine in New York City. He is the Director of the Division of Therapeutic Medical Physics of Montefiore Medical Center and the Director of Medical Physics of the Institute for Onco-Physics at the Albert Einstein College of Medicine. In addition, he also holds appointments as Visiting Professor of Medical Physics at the Centre of Medical Radiation Physics at the University of Wollongong, Australia and the Uni- versity of Wisconsin at Madison. He has over 200 peer-reviewed publications, 16 book chapters, 2 books, over 200 abstracts, 5 patents to his credit, and is a Fellow of the American Association of Medical Physics. His current research interests include: techniques to mitigate normal tissue injury; bio-effects of focused-ultrasound; biologically guided therapy, MR guided therapy, SBRT, as well as immunoadjuvant cancer therapies. Professor Mauro Carrara, PhD Mauro Carrara works as Medical Physicist at the Department of Diagnostic Imaging and Radiotherapy at National Cancer Insti- tute of Milano (Italy) where he is responsible for brachytherapy physics. He conducts research in several fields concerning quality control and dosimetry in high dose rate brachytherapy and the application of US or MR imaging for treatment planning. He has been invited to several national and international conferences to lecture on these subjects. Being part of the multidisci- plinary Prostate Program of his Institution, he is as well involved in the development of non-linear models for acute and late toxicity prediction and the study of highly hypofractionated treatment schemes in prostate high dose radiotherapy. In 2006, he was officially awarded by the Major of Milan with the International Young Researcher Award “Amici di Milano”. He is a member of the European Society for Therapeutic Radiology and Oncology (ESTRO) and Italian Association of Medical Phys- ics (AIFM). For ESTRO and AIFM he was invited to conduct several courses in the fields of dosimetry, radiotherapy physics and mathematical non-linear models for pattern classification. Since 2007 he is Professor at the Department of Medicine and Sur- gery of the University of Milano. He is member of the Editorial Board of Physica Medica: European Journal of Medical Physics (Elsevier) and Section Editor for Tumori Journal (Wichtig). MMND—International Faculty Professor Katia Parodi, PhD Katia Parodi received her Ph.D. in Physics from the University of Dresden, Germany, in 2004. She then worked as postdoctoral fellow at Massachusetts General Hospital and Harvard Medical School in Boston, USA. In 2006 she returned to Germany as tenured scientist and group leader at the Heidelberg Ion Therapy Center, obtaining in 2009 her Habilitation from the Heidel- berg University. Since 2012 she is full professor and Chair of Medical Physics at the Physics Faculty of the Ludwig-Maximilians- University (LMU) in Munich, where she initiated a dedicated curriculum for Medical Physics within the Physics MSc. She also retained a secondary affiliation with the Heidelberg Ion Therapy Center. Her main research interests are in high precision image-guided radiotherapy with a special focus on ion beams, from advanced computational modeling to experimental developments and clinical evaluation of novel methods for in-vivo ion range monitor- ing. Katia Parodi has been invited speaker and committee member at many conferences, and contributed to over 90 publica- tions in peer reviewed journals, more than 150 conference contributions, 5 book chapters and a couple of patents. For her work she received several national and international recognitions, including the Behnken Berger Award in 2006, the IEEE Bruce Hasegawa Young Investigator Medical Imaging Science Award in 2009 and the AAPM John S. Laughlin Young Scientist in 2015. Since 2015 she is also vice president of the German Society for Medical Physics (DGMP). Doctor Suzie Sheehy, PhD Dr. Suzie Sheehy is an accelerator physicist and Royal Society University Research Fellow at the University of Oxford, UK. She leads research in high intensity hadron beams within the John Adams Institute for Accelerator Science, where she also teaches graduate level accelerator physics. Her research uses a combination of theoretical, experimental and simulation-based ap- proaches to address questions in beam dynamics and the design of future accelerators. Her career has led her to study acceler- ators for a range of applications from proton/ion therapy to accelerator driven nuclear waste transmutation. In addition to her research and teaching of graduate level accelerator physics, Dr. Sheehy is also an award winning science communicator and presenter, bringing physics to wider audiences through TV, radio, podcasts, major live shows and demonstration lectures. MMND—International Faculty Professor Taiga Yamaya, PhD Taiga Yamaya, Ph. D, is a Team Leader of Imaging Physics Team at National Institute of Radiological Sciences (NIRS), National Institutes for Quantum and Radiological Science and Technology (QST) in Japan. His research interest is the development of next generation positron emission tomography (PET) systems as well as development of radiation detectors and image recon- struction algorithms. He obtained his Ph. D degree in 2000. He has been awarded more than 10 prizes, one of which was the 1st prize of German Innovation Award (2012). He has accomplished more than 100 peer reviewed publications and more than 50 registered patents. He has also visiting professor positions in Chiba University and Yokohama City University. In Yamaya’s laboratory at NIRS-QST, using their core technologies of depth-of-interaction (DOI) measurement, they are developing a new equipment concept of “OpenPET” for joint PET - therapy imaging and a brain-dedicated PET scanner for earlier diagnosis of dementia. Professor Richard Maughan, PhD Richard Maughan graduated from the University of Birmingham, England with an honors degree in physics in 1970. He com- pleted his Ph.D. in Nuclear Physics at the same institution in 1974. From 1974 to 1983 he worked as a member of the scientific staff of the Cancer Research Campaign Gray Laboratory at Mount Vernon Hospital in England, where he was involved in basic radiation physics, chemistry and biology research. He moved to the USA in the fall of 1983, where he took a position as a med- ical physicist and a member of the faculty in the Radiation Oncology Department of Wayne State University (WSU), in Detroit. He played a major role in the development and application of a superconducting cyclotron as a neutron source for neutron radiation therapy. In July 2000 Dr. Maughan moved to the University of Pennsylvania where he was appointed Professor, Director of Medical Physics and Vice Chair in the Department of Radiation Oncology. In this role he was a key member of the proton therapy devel- opment team, participating in the specification of the system, vendor selection and overseeing acceptance and commissioning. Under his direction the Medical Physics division expanded from about 30 people to a staff of over 80. He stepped down as Divi- sion Director in June 2013 and is currently a Professor and Vice Chair in the department. MMND—International Faculty Professor Zuofeng Li, PhD Zuofeng Li is a Professor of Radiation Oncology at the University of Florida College of Medicine, and serves as the Director of Physics at the University of Florida Health Proton Therapy Institute. He graduated from Washington University in St. Louis with a degree of D.Sc. in Systems Science and Mathematics, and entered medical physics field as a post-doctoral research associate at Washington University School of Medicine. Following completion of medical physics residency training from Washington University, he held successive faculty appointments at University of Florida and Washington University, during which time he led the brachytherapy physics services at these institutions and performed Monte Carlo brachtherapy dosimetry research. Dr. Li returned to University of Florida in 2005 to lead its proton therapy system installation, acceptance testing and commission- ing, and subsequent clinical physics operations. Dr. Li had served on various AAPM task groups on brachytherapy and proton therapy topics, and as the chairman of the AAPM Brachytherapy Subcommmittee, among other AAPM appointments. Dr. Li participated in the training and supervision of 8 PhD graduate students, and more than 20 medical physics residents; and is an author or co-author of over 120 peer-reviewed journal publications. He is a co-recipient of the 1993-1994 Farrington Daniel Award of Medical Physics Journal, and was named a Fellow of AAPM in 2012. MMND ITRO 2018 PROGRAM Tuesday 6th February 2018 MMND multidisciplinary (micro- nano-dosimetry, radiobiology, synchrotron MRT and EBRT, Monte Carlo Modelling) 07:50-08:00 Introduction/Welcome Anatoly Rozenfeld/Tomas Kron /Michael Lerch Physics in Heavy Ion Therapy (Microdosimetry) Session chairs: Anatoly Rozenfeld, CMRP Rui Qiu, Tsinghua University 08:00–08:30 (Invited) Larry Pinsky Update on the status of MEDIPIX in space and an introduction to the Timepix 2 University of Houston, USA 08:30–08:45 Kenta Takada Evaluation of RBE-weighted doses for various radiotherapy beams based on a microdosimetric function implemented in PHITS University of Tsukuba, Japan 08:45–08:55 Davide Bortot Microdosimetry on nanometric scale with a new low-pressure avalanche-confinement TEPC Politecnico di Milano, Italy 08:55-09:05 Davide Mazzucconi A FPGA-based software for microdosimetric data processing Politecnico di Milano, Italy 09:05-09:15 Anatoly Rozenfeld Progress in Silicon microdosimetry and its applications CMRP UOW 09:15-09:25 Jeremy Davis Progress in diamond microdosimetry CMRP UOW 09:25-09:30 Ben James 3D Sensitive Volume Microdosimeter with Improved Tissue Equivalency: Charge Collection Study and its Application in 12C Ion Therapy CMRP UOW 09:30-09:35 Emily Debrot Mini Beam C 12 therapy: simulations and first experimental results with SOI micro dosimeters CMRP UOW Radiobiology & Monte Carlo Simulations Session chairs: Michael Lerch, CMRP; Larry Pinsky, University of Houston 09:35-10:00 (Invited) Roger Martin Topical radioprotection of radiation induced oral mucositis M M N D I T R O 2 0 1 8 P r o g r a m 2 0 1 8 - 0 1 - 2 3 P a g e | 1 MMND ITRO 2018 PROGRAM Peter MacCallum CC 10:00–10:30 Morning Tea 10:30-10:45 Moeava Tehei Progress in Radiobiology CMRP UOW 10:45-11:00 Susanna Guatelli Recent developments in Geant4 for medical physics applications CMRP UOW 11:00-11:15 Dousatsu Sakata Development of track structure models in GEANT 4 on nanometre scale gold CMRP UOW 11:15-11:25 Hilary Byrne Nanotheranostic Radio-Enhancement University of Sydney 11:25-11:30 David Bolst Modelling HIMAC biomedical beamline CMRP UOW 11:30-11:50 (Invited) Rui Qiu Latest development and applications of the Chinese reference phantoms Tsinghua University, Beijing, China Synchrotron Radiation Session chairs: Enbang Li, CMRP; Yoshinori Sakurai, Kyoto University 11:50-12:05 Michael Lerch Progress in MRT research towards clinical implementation CMRP UOW 12:05-12:20 Olga Martin Localised synchrotron radiation in mice induced persistent systemic genotoxic events mediated by the functional immune system Peter MacCallum CC 12:20-12:25 Elette Engels Towards image guided MRT CMRP UOW 12:25-12:30 James Archer Fibre optic dosimetry in synchrotron microbeam radiation therapy CMRP UOW 12:30 – 13:30 Lunch M M N D I T R O 2 0 1 8 P r o g r a m 2 0 1 8 - 0 1 - 2 3 P a g e | 2 MMND ITRO 2018 PROGRAM Space Dosimetry Session chairs: Dale Prokopovich, ANSTO; Kenta Takada, University of Tsukuba 13:30–14:00 (Invited) Taku Inaniwa Progress of the microdosimetric kinetic model in heavy-ion therapy National Institute for Quantum and Radiological Science and Technology, Japan 14:00–14:15 Stuart George High Precision Track Geometry Calculation in Hybrid-Pixel Detectors University of Houston, USA 14:15–14:25 Stefania Peracchi Simulation of cosmic radiation spectra for personal microdosimetry at the International Space Station altitude CMRP UOW Radiation Therapy Session chairs: Tomas Kron, Peter McCullum CC; Wolfgang Tome, AECM 14:25–14:45 (Invited) Vladimir Feygelman Preview of AAPM Working Group recommendations for TPS reference dose specification Moffitt CC, USA 14:45-15:00 Nicholas Hardcastle The liver INSPECTR trials: towards improved understanding of liver function following radiotherapy. Peter MacCallum CC 15:00-15:30 Afternoon Tea 15:30-15:45 Yang Wang Characterisation Evaluation for Different QA techniques Clinically Used for IMRT, VMAT and SBRT/SRS Treatment Plan dosimetry verification ICON-Cancer Care 15:45-16:00 Prabhakar Ramachandran A comprehensive phantom with multi-detector inserts for Pre- treatment quality assurance in stereotactic ablative radiotherapy Peter MacCallum CC M M N D I T R O 2 0 1 8 P r o g r a m 2 0 1 8 - 0 1 - 2 3 P a g e | 3 MMND ITRO 2018 PROGRAM MRI-LINAC Session chairs: Peter Metcalfe, CMRP; Grazia Gambarini , INFN 16:00 – 16:15 Taghreed Al-Sudani Build up dose characteristics with eXaSkin bolus during 6MV radiotherapy: MOSkin dosimetry results CMRP UOW 16:15 - 16:25 Trent Causer Characterization of monolithic silicon strip detectors for MRI- Linac dosimetry CMRP UOW 16:25- 16:35 Natalia Roberts Modelling the X-ray source for the Australian MRI-linac CMRP UOW Boron Neutron Capture Therapy Session chairs: Susanna Guatelli, CMRP; Richard Maughan, University of Pennsylvania 16:35–16:55 (Invited) Yoshinori Sakurai Fundamental knowledge for microdosimetry in boron neutron capture therapy Kyoto University, Japan 16:55–17:15 (Invited) Grazia Gambarini BNCT Dosimetry: Peculiarities and Methods University of Milan, Italy 17:15–17:25 James Vohradsky Evaluation of silicon and diamond based microdosimetry for boron neutron capture therapy applications CMRP UOW 17:25–17:35 Andrew Chacon Neutron Capture Enhanced Particle Therapy: Opportunistic Dose Amplification via Capture of Thermal Neutrons Produced During Heavy Ion and Proton Therapy CMRP UOW and ANSTO M M N D I T R O 2 0 1 8 P r o g r a m 2 0 1 8 - 0 1 - 2 3 P a g e | 4 MMND ITRO 2018 PROGRAM Wednesday 7th February 2018 Brachytherapy Day 07:50-08:00 Introduction and Welcome Anatoly Rozenfeld, Michael Zelefsky and Josh Yamada What is New In Brachytherapy? Session chairs: Josh Yamada, MSKCC; Michael Jackson , POWH 08:00–08:30 (Invited) Mira Keys 20 minutes + 10 min QA/Discussion Why Brachytherapy? Implication on long term outcomes University of British Columbia, Vancouver, BC, Canada 08:30–09:00 (Invited) Michael Zelefsky Improving Dosimetric Outcomes of Prostate Cancer with Real Time Imaged-Based Feedback Memorial Sloan Kettering Cancer Center, New York 09:00 – 09:40 (Invited) Antonio Damato Advances in brachytherapy physics (30 min+10 min Q/A Discussions) a. US/EM guidance b. Active MRI guidance Memorial Sloan Kettering Cancer Center, New York 09:40 – 10:00 (Invited) Mauro Carrara New Trends in dose calculations, delivery and in vivo verification in brachytherapy (20 min+5 min Q/A Discussions) Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy 10:00 – 10:30 Morning Tea Physics Innovations Session chairs: Anna Ralston, SG CCC; Mauro Carrara , National CC Milan 10:30 – 11:00 (Invited) Antonio Damato Directional brachytherapy- (20 min + 10 min discussion/QA) Memorial Sloan Kettering Cancer Center, New York 11:00 – 11:15 Anatoly Rozenfeld BrachyView: new technology for online source tracking in brachytherapy CMRP UOW 11:15 – 11:30 Yu Sun Use of Contemporary imaging methods in brachytherapy applications University of Sydney 11:30 – 11:40 Taylah Brennen Eye brachytherapy: new technology for fast QA of eye plaques CMRP UOW M M N D I T R O 2 0 1 8 P r o g r a m 2 0 1 8 - 0 1 - 2 3 P a g e | 5 MMND ITRO 2018 PROGRAM 11:40 – 11:50 Anna Romanyukha Gynaecological HDR BT applicator for treatment delivery and online QA verification of source dwell positions and times CMRP UOW 11:50 – 12:00 Dean Cutajar End to End (E2E) QA phantom for TRUS guide HDR brachytherapy CMRP UOW and SG CCC 12:00 – 12:20 (Invited) Prabhakar Ramachandra Brachytherapy utilising miniaturised X-ray tubes – An evolving technology Peter MacCallum Cancer Centre 12:20 – 12:30 Adam Yeo On line IGBT for prostate cancer ultrasound based real time solution Peter MacCallum Cancer Centre 12:30 – 13:30 Lunch Debate: SBRT vs Brachytherapy for localised prostate cancer Session chairs:Michael Folkert , UT Southwestern Medical Center; Michael Jackson , POWH 13:30 – 14:00 (Invited) Michael Zelefsky 20 minutes + 10 min QA/Discussion Memorial Sloan Kettering Cancer Center, New York 14:00 – 14:30 (Invited) Mira Keyes 20 minutes + 10 min QA/Discussion University of British Columbia, Vancouver, BC, Canada Tumour Board: Challenging Cases Session chairs: Josh Yamada, MSKCC 14:30 – 15:00 Michael Zelefsky, Mira Keyes, Joe Bucci, Michael Folkert/other incl. local Doctors 15:00 – 15:30 Afternoon Tea Skin Brachytherapy: Session Chairs: Bryan Burmeister, Radiation Oncology Centres(ROS) Fraser Coast and Redland Australia 15:30 – 16:00 (Invited) Chris Barker, New Approaches to Skin Cancer Brachytherapy MSKCC, New York Partial Breast Brachytherapy Session chairs: Mira Keys, University of British Columbia , Joseph Bucci , SG CCC 16:00 – 16.25 (Invited) Sean Park Same Day OperatioN and Intraoperative Catheter placement for Partial Breast Irradiation (SONIC-PBI) Mayo Clinic, USA M M N D I T R O 2 0 1 8 P r o g r a m 2 0 1 8 - 0 1 - 2 3 P a g e | 6 MMND ITRO 2018 PROGRAM 16:25 – 16:50 (Invited) Michael Folkert Ablative interstitial high-dose rate brachytherapy for localised visceral primary and metastatic lesions UT Southwestern Medical Center, USA Thursday 8th February 2018 Particle Therapy Day Advanced Heavy Ion and Proton Therapy Technology Session chairs: Anatoly Rozenfeld, CMRP; Michael Jackson , POWH 08:00 – 8:25 (Invited) Koji Noda Recent progress and future plan of heavy-ion-cancer radiotherapy with HIMAC National Institute for Quantum and Radiological Science and Technology, Japan 08:25 – 8:50 (Invited) Richard Maughan Recent Developments at the University of Pennsylvania’s Roberts Proton Therapy Center Penn University, USA 08:50 – 9:15 (Invited) Zuofeng Li, IBA Image-Guided Adaptive Proton Therapy IBA: Proton Therapy Center, Florida University, USA 09:15 – 9:40 (Invited) Masumi Umezawa Hitachi Recent developments in Hitachi’s Hybrid Therapy Solution Hitachi 09:40 – 10:00 (Invited) Mauro Carrara Italian medical physicists' and radiation oncologists' view on hadron therapy Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy 10:00 – 10:30 Morning Tea QA in Proton Therapy and Treatment Optimization Session chairs: Carl Rossi , Scripps Proton Therapy Center; Tomas Kron , Peter MacCallum CC 10:30 – 10:45 Irene Gudowska Out-of-field doses associated with proton therapy Stockholm University, Stockholm, Sweden 10:45 – 11.00 Tina Pfeiler 4D Robust optimization in pencil beam scanning proton therapy for hepatocellular carcinoma The West German Proton Therapy Centre Essen, Germany 11:00 – 11:15 Jed Johnson Efficient patient-specific QA for spot-scanned proton therapy using nozzle-integrated detectors and fast Monte Carlo dose calculations Mayo Clinic, USA M M N D I T R O 2 0 1 8 P r o g r a m 2 0 1 8 - 0 1 - 2 3 P a g e | 7 MMND ITRO 2018 PROGRAM 11:15 – 11:30 (Invited) Roberto Sacchi Test of innovative silicon detectors for the monitoring of a therapeutic proton beam University of Torino and INFN, Italy 11:30 – 11:45 Daniel Mundy Development of the Dose Magnifying Glass for clinical proton range measurements Mayo Clinic, USA 11:45-12:10 (Invited) Marco Silari GEM detectors for use in particle therapy CERN 12:10-12:30 (Invited) Benjamin Clasie Installation of a compact comprehensive proton therapy unit via an elevator shaft into existing standard radiotherapy centre MGH, USA 12:30 – 13:30 Lunch Imaging with Protons and Ions Session chairs: Marie-Claude Gregoire, ANSTO; Scott Penfold , RAH 13:30 – 13:55 (Invited) Katia Parodi Ionoacoustics for range monitoring of proton therapy LMU Munich, Germany 13:55 – 14:20 (Invited) Taiga Yamaya In-beam OpenPET imaging for RI beams National Institute for Quantum and Radiological Science and Technology, Japan 14:20 – 14:45 (Invited) Katia Parodi Prompt gamma range monitoring of proton therapy status and perspectives LMU Munich, Germany 14:45 – 15:00 Melek Zarifi In-vivo range verification in hadron therapy using prompt gamma rays: A Geant4 simulation study CMRP UOW 15:00 – 15:30 Afternoon Tea 15:30 – 15:45 Brad Oborn MRI guided proton therapy: current status of development CMRP UOW 15:45 – 16:00 Mitsutaka Yamaguchi Simulation study on imaging of a monochromatic carbon beam by measuring secondary electron bremsstrahlung National Institute for Quantum and Radiological Science and Technology, Japan M M N D I T R O 2 0 1 8 P r o g r a m 2 0 1 8 - 0 1 - 2 3 P a g e | 8 MMND ITRO 2018 PROGRAM 16:00 – 16.20 (Invited) Dieter Roehrich The Bergen proton CT project – proton tracking in a high- granularity digital tracking calorimeter University of Bergen, Norway Australian Proton Therapy Project Session chairs: Koji Noda, National Institute for Quantum and Radiological Science and Technology; Verity Ahern . The Crown Princess Mary CC Westmead 16.20 – 16:40 (Invited) Michael Penniment Australian Proton Therapy Project Royal Adelaide Hospital, South Australia 16:40 – 16:55 Scott Penfold Dual Energy yCBCT for adaptive proton therapy: A feasibility study Royal Adelaide Hospital, South Australia Fundamental Physics of Ions Interaction and New Accelerator Technology in Particle Therapy Session chairs Igor Bray, Curtin University; Dale Prokopovich, ANSTO 16:55-17:10 (Invited) A.S. Kadyrov Comprehensive approach to hadron interactions with matter Curtin University, Perth Western Australia 17:10-17:25 Edward Simpson Nuclear reaction cross sections for Hadron therapy ANU, Canberra ACT 17:25-17:50 (Invited - Special Closing) Suzie Sheehy Can novel accelerator technology improve proton/ion therapy? Oxford University, UK 17:50-18:00 Anatoly Rozenfeld Close and future meeting CMRP UOW M M N D I T R O 2 0 1 8 P r o g r a m 2 0 1 8 - 0 1 - 2 3 P a g e | 9 Physics in Heavy Ion Therapy (Microdosimetry) UPDATE ON THE STATUS OF MEDIPIX IN SPACE AND AN INTRODUCTION TO THE TIMEPIX2 Lawrence Pinsky1 1 Physics Department, University of Houston, Houston, TX 77204-5005 USA, pinsky@uh.edu Introduction: This paper updates the status of the use of technology developed by the CERN-based Medipix Collaborations in space radiation monitor- ing coupled with future plans including a look at the promise of the long anticipated Timepix2 device. Background: NASA has flown Timepix-based Radiation Environment Monitors (REMs) onboard the International Space Station (ISS) since 20121. Furhter, Timepix-based devices were the sole active radiation monirors onboard the first test on the new Multi-Purpose Crew Vehicle (MPCV, or “Orion”) in December, 2014. Another Timepix-based device, the Hybrid Electroic Radiation Assessor, (HERA), is being deployed on the upcoming full trans-lunar test of the Orion spacecraft on Exploration Mission-1 (EM-1), and plans are in place to use the same or similar hardware on EM-2, the first manned mission above Low Earth Orbit (LEO) since Apollo. In addi- tion to NASA’s use of this technology in space, a number of satellite experiments have flown Timepix- based devices, including Proba V, Satram, and LUCID on the UK’s TechDemo1 mission. Similar future applications of this and follow-on versions of this technology are actively being pursued within a number of upcoming projects Timepix: The Timepix from the CERN-based Medipix2 Collaboration1 is a hybrid pixel device consisting of detector chip having 256 x 256 pixels, each of which are 55 µm square using 250 nm IBM CMOS. The top surface of the chip has a solder pad enabling the connection of the chip to an overlying sensor chip with cooresponding solder pads using the Flip-Chip® solder-bump bonding technology. The sensor chip typically is a bulk semi-conductor with opposing polarity implants over each solder-bump pad. A reversed bias voltage is applied between the top surface of the sensor and the solder bumps via the front-end amplifiers in the Timepix chip. This allows the digitization of the total net charge collect- ed from the electron-hole pairs produced by the dep- osition of energy in the bulk semiconductor of the sensor by an ionizing charged particle. The Timepix pixels each contain the analog and digital circuitry to digitize the amount of charge deposited using a Wil- ikison-type Time-Over-Threshold (TOT) technique. This allows the visualization of the tracks of pene- trating charged particles and the determination of the energy deposited during each charged particle’s transit within the sensor volume. Timepix2: The Medipix2 Collaboration has been in the process of designing a second generation of the Timepix chip, motivated by the widespread success of the Timepix in its application to a wide variety of situations. The Timepix2 is a complete re-design of the Timepix using 135 nm TSMC CMOS. In addi- tion to including simultaneous recording of both TOT charge measurement and Time Of Arrival (TOA) within 10 ns encoding, several and improve- ments have also been added. These include provi- sions for excluding residual charge collection from events that occurred prior to the “Shutter Open” and including the continuation of readouts for pixels that are still digitizing after the “Shutter Closes.” Another important change regards the analog in- put treatment. A new design with active feedback extends the input range to well over 3 MeV of energy deposited in the sensor being collected per pixel within the dynamic range for digitization. Charge depositions greater than that limit will be clamped to a constant plateau value, avoiding so-called “volcano effect” seen in the current Timepix. Acknowledgments: The contrbutions and sup- port of Stuart George, Thomas Campbell-Ricketts, and Anton Empl, from the University of Houston, asa well as Daniel Turecek (Also with ADVACAM s.r.o.), and Lukas Tlustos (also with CERN). Contri- butions and support also comes from the members of the Space Radiation Analysis Group at NASA’s Johnson Space Center (JSC) including Edward Se- mones, Martin Kroupa, Nicholas Stoffle, Ryan Rios, Dan Fry, Ramona Gaza, and all of the support per- sonnel at JSC who have contributed to the success of the Timepix-based devices in space radiation moni- toring. References: 1. A semiconductor radiation imaging pixel detector for space radiation dosimetry, M. Kroupa, et al., Life Sci Space Res. 6, 69-78 (2015). 2. Timepix, a 65k programmable pixel readout chip for arrival time, energy and/or photon counting measurements, (Llopart, X., et al.), Nucl. Inst. And Meth. Phys. Res. A 581, 485-494 (2007); and erratum Nucl. Instr. and Meth. A 585, 106 (2008). Tuesday 6th of February 08:00 EVALUATION OF RBE-WEIGHTED DOSES FOR VARIOUS RADIOTHERAPY BEAMS BASED ON A MICRODOSIMETRIC FUNCTION IMPLEMENTED IN PHITS Kenta Takada1, Tatsuhiko Sato2, Hiroaki Kumada1, Hideyuki Sakurai1, Takeji Sakae1 1 Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan 2 Japan Atomic Energy Agency, 2-4, Shirakata, Tokai, Ibaraki 319-1195, Japan Corresponding author: k-takada@md.tsukuba.ac.jp Introduction: The University of Tsukuba devel- oped a treatment planning system (TPS) for boron neutron capture therapy (BNCT) that uses a Monte Carlo algorithm as a dose calculation engine. In the near future, the use of this TPS will be expanded into radiation therapies other than BNCT (i.e., X-ray therapy, and particle therapies). Based on this TPS, we will conduct a biological dose estimation and a physical dose evaluation considering the relative biological effectiveness (RBE). To achieve this pur- pose, we constructed a Monte Carlo calculation ge- ometry for various radiotherapy beams and calculat- ed the dose probability density of lineal energy (y): d(y) and the biological dose using the appropriate geometry and PHITS code. Materials and Methods: The yd(y) spectra for the various types of radiation beams, namely X-ray beams (10 MV, 200 keV), a proton beam (200 MeV), a carbon-ion beam (290 MeV/u), and an accelerator- based BNCT beam, were calculated. The yd(y) spec- tra were calculated using the microdosimetric func- tion implemented in PHITS code [1]. The RBE- weighted dose distributions for a charged particle beam were also calculated in combination with the microdosimetric kinetic model [2]. The double scat- terer method and the wobbler irradiation methods were assumed to be the irradiation methods of the proton and carbon-ion beams, respectively. The width of the spread-out Bragg peak was 60 mm. With regard to the BNCT beam, an accelerator-based neutron source developed by the University of Tsu- kuba, which was a neutron beam generated by irradi- ating a proton beam of 8 MeV onto a beryllium tar- get [3], was evaluated. Results: Figure 1 shows the relative comparison of the yd(y) spectra for various beams. Sharp peaks were observed at approximately a y-value of 1 (keV/μm) in the calculated yd(y) spectrum of the 10 MV X-rays. This peak was attributed to the produc- tion of Auger electrons from an oxygen atom. In the yd(y) spectrum of the carbon-ion beam, two peaks were observed in the yd(y) spectrum calculated by PHITS. These two peaks were caused by the contri- bution of the primary component of the carbon-ion and δ rays. The peak around 5 keV/μm can not be observed with a thick-walled detector. Figure 2 presents the calculated physical and RBE-weighted dose dis- tributions for the carbon-ion beam in the water phan- tom. The calculated depth doses were nearly agreed with the measured data obtained by using a tissue equivalent proportional counter [4]. Conclusions: The microdosimetric yd(y) spectra and the RBE-weighted dose for various radiation beams were calculated. By implementing this meth- od, the newly developed TPS at the University of Tsukuba can be expected to calculate the RBE- weighted dose along with the physical dose for vari- ous radiotherapy beams. References: 1. Sato T, Watanabe R and Niita K 2006 Radiat. Prot. Dosim. 122 41-5 2. Hawkins R B 1998 Med. Phys. 25 1157-70 3. Kumada H, Matsumura A, Sakurai H, et al. 2014 Appl. Radiat. Isot. 88 211-5 4. Kase Y, Kanai T, Sakama M, et al. 2011 J. Radi- at. Res. 52 59-6 Figure 2. Comparison of physical and RBE-weighted dose for car- bon-ion beam. Figure 1. Calculated yd(y) spectra for various radiotherapy beams. Tuesday 6th of February 08:30 MICRODOSIMETRY ON NANOMETRIC SCALE WITH A NEW LOW-PRESSURE AVALANCHE-CONFINEMENT TEPC D. Bortot1,2, D. Mazzucconi1,2, S. Agosteo1,2, A. Pola1,2, S. Pasquato1,2, A. Fazzi1,2, P. Colautti3,V. Conte3 1 Politecnico di Milano, Energy Department, via La Masa 34, 20156 Milano, Italy, davide.bortot@polimi.it 2 INFN, Sezione di Milano, via Celoria 16, 20133 Milano, Italy. 3 INFN, Laboratori di Legnaro, viale dell’Università 2, Legnaro, Padova, Italy. Introduction: The tissue equivalent proportional counter (TEPC) is the most accurate device for measuring the microdosimetric properties of a parti- cle beam, nevertheless no detailed information on the track structure of the impinging particles can be ob- tained, since the lower operation limit of common TEPCs is about 0.3 μm1. On the other hand, the pat- tern of particle interactions is measured by track- nanodosimetry, which derives the single-event distri- bution of ionization cluster size at the nanometric scale. However, only three nanodosimeters are avail- able worldwide, showing stringent limitations: com- plexity, dimension and associated lack of transporta- bility. In order to fill the gap between standard TEPCs and nanodosimeters, an innovative ava- lanche-confinement TEPC capable of simulating biological sites down to the nanometric region was designed and constructed. Materials and Methods: Since the lower opera- tion limit of single-wire TEPCs is equal to about 300 nm in order to maintain an acceptable energy resolu- tion, it is necessary to modify the geometry of the sensitive volume by embedding a third electrode for confining the electronic avalanche within a defined region. An extensive study, based on a prototype described elsewhere2, allowed designing and devel- oping an avalanche-confinement TEPC (sensitive volume 13 mm in diameter and length) which houses three electrodes biased independently: a central an- ode wire (graphite), a cylindrical cathode shell (con- ductive plastic A-150 type) and a helix (gold-plated tungsten), which surrounds the anode and subdivides the sensitive volume into an external drift zone and an internal multiplication region (Figure 1). Two aligned cavities embed a removable 244Cm alpha source and a very compact solid-state detector: this configuration allows calibrating the TEPC by also varying the simulated site size and the polarization of the three electrodes. It guarantees that only signals due to alpha particles with a straight path inside the sensitive volume, i.e. the drift region, are collected3. Figure 1. Cross-sectional view of the new TEPC. A customized and transportable vacuum and gas flow system guarantees vacuum conditions and en- sures a continuous replacement of tissue equivalent gas inside the chamber. Dimethyl ether (DME: (CH3)2O), which can be considered as a tissue- equivalent gas apart from the lack of nitrogen, is the selected filling gas for this TEPC. Results: The TEPC response in the range 0.3 μm- 25 nm against a fast neutron field produced by a cal- ibrated 241Am-Be source and quasi-monoenergetic neutron beams produced through the 7Li(p,n)7Be reaction on a LiF target was assessed experimentally. Two further characterizations with 62 MeV/u carbon ion and helium ion beams were performed at the INFN-Laboratori Nazionali del Sud (LNS-INFN). The experimental response of the microdosimeter for different simulated site sizes in the range 300-25 nm at several points across the depth dose distribution was measured and compared with Monte Carlo simu- lations performed with the FLUKA code. The ob- tained results show a rather good agreement. Conclusions: The irradiation campaigns with dif- ferent neutron beams and low-energy hadrons (heli- um and carbon ions) give confidence about the capa- bility of this novel avalanche-confinement TEPC of measuring microdosimetric distribution at simulated site ranging from 0.3 μm down to 25 nm. Further irradiations with other particles are necessary to study deeply the charge collection efficiency of the TEPC at low simulated site sizes, i.e. down to 25 nm. Moreover, further comparisons between FLUKA simulation and experimental data measured with oth- er particles are foreseen. Acknowledgements: This work was supported by the Italian National Institute for Nuclear Physics - INFN – Scientific Commission V in the framework of the MITRA (Microdosimetry and TRAck struc- ture) and NADIR (biologically relevant NAno- Dosimetry of Ionizing Radiation) projects. References: 1. B. Hogeweg, Proc. 4th Symp. on Microdosimetry 5122, 843-854 (1973). 2. V. Cesari et al., Radiat. Prot. Dosim. 99, 337-342 (2002). 3. D. Bortot et al., Radiat. Meas. (2017). https://doi.org/10.1016/j.radmeas.2017.01.01 Tuesday 6th of February 08:45 A FPGA-BASED SOFTWARE FOR MICRODOSIMETRIC DATA PROCESSING D. Mazzucconi1,2, M. Bonfanti1,2, D. Bortot1,2, S. Agosteo1,2, A. Pola1,2, S. Pasquato1,2, A. Fazzi1,2 1 Politecnico di Milano, Energy Department, via La Masa 34, 20156 Milano, Italy, davide.mazzucconi@polimi.it 2 INFN, Sezione di Milano, via Celoria 16, 20133 Milano, Italy. Introduction: Microdosimetry describes the sta- tistical fluctuations of the imparted energy in a mi- crometric site1. The tissue equivalent proportional counter (TEPC) is the most accurate device for measuring the microdosimetric properties of a parti- cle beam. Since microdosimetric quantities (i.e. the specific energy and the lineal energy) may span over several decades, the electronic and acquisition chain should meet further requirements with respect to the conventional one. Usually, in order to cover the wide dynamic range of the signals generated by the TEPC and to ensure a good resolution throughout this range, the output signal from the preamplifier is fed in parallel to three linear amplifiers which shape and amplify the signal with different gains. In such a way, very low energy deposition events are filtered in the high-gain stage, and high-energy deposition events, which necessarily saturate in the high-gain stage, are processed in the low-gain stage. The acqui- sition chain should be capable of processing and merging the signals coming from the three amplifi- ers. A new system with high acquisition perfor- mance, in terms of real time calculations, and com- pact hardware was developed for this purpose. Materials and Methods: The analog-to-digital conversion is performed by a commercial acquisition system produced by National Instruments, the 4 channels, 14 Bit-Oscilloscope NI PXIe-5170R, which is a configurable digitizer including a user- programmable FPGA (Field Programmable Gate Array) module for the on-board signal processing. The FPGA module is an integrated circuit that con- tains a matrix of reconfigurable gate array logic cir- cuitry that is programmed via software. When an FPGA is configured, the internal circuitry is connect- ed in a way that creates a hardware implementation of the software application. In this way, the FPGA is capable of performing high speed parallel computa- tions on the acquired data. The FPGA circuitry is programmed thanks to LabVIEW FPGA module2, which belongs to the high-level LabVIEW graphical programming environment. LabVIEW FPGA devel- opment tools also contain a built-in FIFO (First In First Out) transfer and memory read/write functions for storing data in the FPGA application. The FIFO transfer is the connecting bridge between the FPGA and the elaboration software which gives the micro- dosimetric spectrum. Thanks to the FPGA module a parallel high speed acquisition on the three channels can be performed. Moreover, the implemented soft- ware can merge together the three electronic chains and compute a real time microdosimetric spectrum. Figure 1. Graphical interface of the software showing a spectrum from an Am-Be fast neutron source. Results: The developed software has a graphical interface in which the user can set the acquisition parameters (e.g. sampling rate and acquisition thresholds) and visualize the microdosimetric spec- trum. The FPGA software can perform analog-to- digital conversion and digital signal processing at a sampling rate up to 15 MS/s (i. e. Mega Samples per second) per each of the three channels (The ADC speed is 45 MS/s). The software can plot a real time microdosimetric spectrum in order to have a prompt information about the irradiation field (Figure 1). Conclusions: The new FPGA-based hardware and software, allow to reach a significant high acqui- sition speed that is needed in the presence of a high counting rate. This is because, for intense fields, a shorter shaping time is mandatory in order not to cause a pulse pile-up. The new acquisition software was tested irradiating a TEPC with an intense quasi- monoenergetic neutron beam and a 62 MeV/u helium ion beam. Further optimization on the FPGA archi- tecture is foreseen in order to achieve an improve- ment on the computation performances. Acknowledgements: This work was supported by the Italian National Institute for Nuclear Physics - INFN – Scientific Commission V in the framework of the MITRA (Microdosimetry and TRAck struc- ture) and NADIR (biologically relevant NAno- Dosimetry of Ionizing Radiation) projects. References: 4. Microdosimetry. ICRU Report 36 (1983). 2. National Instruments. http://www.ni.co Tuesday 6th of February 08:55 PROGRESS IN SILICON MICRODOSIMETRY AND ITS APPLICATIONS Linh T. Tran1, David Bolst1, Emily Debrot1, Susanna Guatelli1, Marco Petasecca1, Michael Lerch1, Lachlan Chartier1, Dale Prokopovich1, Marco Povoli2, Angela Kok2, Charlot Vandevoorde3, J. Slabbert3, Naruhiro Matsufuji4, Tatsuaki Kanai5, Anatoly B. Rosenfeld1 1Centre for Medical Radiation Physics, University of Wollongong, Australia. anatoly@uow.edu.au 2SINTEF, Norway 3Radiation Biophysics Department, NRF iThemba LABS, South Africa 4National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan 5Gunma Heavy Ion Medical Centre, Gunma, Japan The solid state microdosimeters with 3D micron sized sensitive volumes (SVs) mimicking dimensions of cells, known as the “Bridge” and “Mushroom” mi- crodosimeters, were fabricated using MEMS technolo- gy [1,2]. The silicon microdosimeters provide extreme- ly high spatial resolution and were used for evaluating the relative biological effectiveness (RBE) of 290 MeV/u 12C, 180 MeV/u 14N and 400 MeV/u 16O pas- sive ion beams as well as 290 MeV/u 12C mini ion beams at Heavy Ion Medical Accelerator in Chiba (HIMAC), Japan. Additionally, the variation of RBE in-field was investigated for a passive proton beam delivery system at iThemba labs, South Africa includ- ing radiobiological and microdosimetry measurements. For a 180 MeV/u 14N pristine BP, the 𝑦𝑦𝐷𝐷��� changed from about 29 keV/µm at the entrance to 92 keV/µm at the BP, with a maximum value 438 keV/µm at the dis- tal edge. For a 400 MeV/u 16O ions, the dose-mean lineal energy 𝑦𝑦𝐷𝐷��� changed from about 24 keV/µm at the entrance to 106 keV/µm at the BP, with a maxi- mum value of approximately 381 keV/µm at the distal edge. The maximum derived RBE10 values for 14N and 16O ions are 3.10 ± 0.47 and 2.93 ± 0.45, respec- tively. The 𝑦𝑦𝐷𝐷��� and RBE10 values are compared for 290 MeV/u 12C broad beam and minibeams produced by brass multi-slit collimator where microdosimetric spectra were measured in peaks and valley and out of field with a recently developed single 3D SV micro- dosimeter. The RBED (D=2Gy) derived from survival of the Chinese Hamster Ovary (CHO) cells and the predicted RBE from the microdosimetric measurements using MKM in proton beam at iThemba labs indicate that there is a strong increase in the biological effectiveness with depth along the SOBP particular in the distal fall off of the SOBP (Fig 1, 2). Both RBED are matching reasonably well. Fig. 1 Petri-dishes representing colony survival in CHO-K1 cells at 6 positions (from left to right: 74.88%, 101.10%, 83.44%, 57.18%, 39.76% and 18.98% of along the Bragg curve, exposed to doses of 4 Gy (2 top rows) and 8 Gy (2 bottom rows). Fig. 2 Comparison of RBED obtained with microdosimetric probe and radiobiological experiment with CHO cells References: 1. Novel detectors for silicon based microdosimetry, their concepts and applications (A. Rosenfeld), Nucl. Instrum. Methods., Phys. Res. A 809, 156– 170, (2016). 2. 3D Silicon Microdosimetry and RBE study us- ing 12C ion of different energies (L. Tran et al.), IEEE Trans. on Nucl. Sci. vol. 62, no. 6, pp 3027- 3033, (2015). Tuesday 6th of February 09:05 3D SENSITIVE VOLUME MICRODOSIMETER WITH IMPROVED TISSUE EQUIVALENCY: CHARGE COLLECTION STUDY AND ITS APPLICATION IN 12C ION THERAPY Benjamin James1, Linh T. Tran,1, David Bolst1, Dale Prokopovich2, Michael Lerch, Marco Petasecca, Susanna Guatelli, Mark Reinhard2, Marco Povoli3, Angela Kok3, Naruhiro Matsufuji4 and Anatoly Rozenfeld1 1Centre of Medical and Radiation Physics, University of Wollongong, bj197@uowmail.edu.au 2NSTLI Nuclear Stewardship, Australian Nuclear Science and Technology Organization, Australia 3SINTEF, Norway 4National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan Introduction: Particle therapy has many ad- vantages over conventional photon therapy, particular- ly for treating deep-seated solid tumours due to its greater conformal energy deposition achieved in the form of the Bragg Peak (BP). Successful treatment with heavy ions depends largely on knowledge of the relative biological effectiveness (RBE) of the radiation produced by primary and secondary charged particles. Different methods and approaches are used for calcula- tion of the RBE-weighted absorbed dose in treatment planning system (TPS) for heavy ion therapy. The RBE derived based on microdosimetric approach using the tissue equivalent proportional counter (TEPC) measurements in 12C therapy has been reported, how- ever the large size of commercial TEPCs averages RBE values which dramatically changes close to and in the distal part of the BP, which may have significant clinical impact. The Centre for Medical Radiation Physics (CMRP), University of Wollongong, has initi- ated the concept of silicon microdosimetry to address the shortcomings of the TEPC[1]. In the course of this research, a new 3D SV microdosimeter covered with a tissue equivalent material has been investigated and its application in C-12 therapy has been studied. Methods: A new generation 3D microdosimeter design was proposed by CMRP, it has 3D cylindrical sensitive volumes, known as “Mushrooms”. The Mushroom microdosimeter is fabricated on silicon on insulator material with a buried oxide layer that iso- lates the sensitive volumes from the support wafer. An array of n+ electrodes and surrounding ring p+ elec- trodes are produced using deep reactive ion etching, followed by polysilicon deposition and doping[1]. In order to improve the tissue equivalence of the new microdosimeters, they have been covered with a 12μm layer of polymide. While the polymide layer will serve to improve the tissue equivalence of the microdosime- ter, charge collection and uniformity studies were re- quired to understand how the microdosimeter output would be affected by this new layer. The charge collection efficiency was investigated using ion beam induced charge collection (IBICC) technique with the 6MV SIRIUS Tandem Accelerator at Australian Nuclear Science and Technology Organi- sation (ANSTO). Median energy maps showing the charge collection characteristics of the device were then created[1]. Finally to study its possible applica- tions in 12C therapy, the new polymide mushroom mi- crodosimeters were placed in various positions along the central axis of the SOBP of a 290 MeV/u 12C ion beam at the Heavy Ion Medical Accelerator in Chiba (HIMAC), Japan. Results: Results presented will include IBIC MCA spectra and median energy maps obtained using the scanning 5.5 MeV He2+ microbeam. These results will demonstrate a uniform charge collection and some issues with the polymide coating deposition, which have been investigated. Based on the irradiations con- ducted at HIMAC, microdosimetric spectra, dose mean lineal energy (yD) and RBE results will also be pre- sented. RBE values obtained in the SOBP at HIMAC showed a dramatic increase, with values of 1.3 ob- served at the entrance and increasing to 2.7 at the end of the SOBP. Conclusions: These results will serve to prove that the new generation, tissue equivalent, polymide mush- room microdosimeters are an excellent tool for quality assurance in heavy ion therapy applications References: 1. Tran, L. T., Chartier, L., Prokopovich, D. A., Rein- hard, M. I., Petasecca, M., Guatelli, S., Lerch, M. L. F., Perevertaylo, V. L., Zaider, M.,Matsufuji, N., Jackson, M., Nancarrow, M. & Rosenfeld, A. B. (2015). 3D-mesa 'bridge' silicon microdosimeter: charge collection study and application to RBE studies in 12C radiation therapy. IEEE Transac- tions on Nuclear Science, 62 (2), 504-511. Tuesday 6th of February 09:25 Radiobiology & Monte Carlo Simulations TOPICAL RADIOPROTECTION OF RADIATION-INDUCED ORAL MUCOSITIS Pavel N. Lobachevsky1, Andrea Smith1, Laura Munforte1, Nevena Vasilijevic1, Sarah Foenander1, Jonathan M. White2, Colin Skene2, Seb Marcuccio3, Roger F. Martin1,3 1Peter MacCallum Cancer Centre, Melbourne, VIC, Australia, rfm@unimelb.edu.au 2School of Chemistry and Bio21 Institute, The University of Melbourne, Melbourne, VIC, Australia, 3Advanced Molecular Technologies, Scoresby, VIC, Australia, Introduction: Even with the most modern radio- therapy techniques, some dose to nearby normal tis- sues cannot be excluded. Many of the normal tissues "at risk" in RT are accessible topically, and the topi- cal application route provides the opportunity to se- lectively protect normal tissues to the exclusion of the tumour. Examples include oral mucosa, rectal mucosa, oesophagus, lung (aerosol), urethra and bladder, hair follicles and skin. We have developed new radioprotecting drugs that can be applied topi- cally to ameliorate normal tissue toxicities in cancer radiotherapy (RT) patients. The initial focus is the clinical scenario of topical application of radiopro- tector to oral mucosa of H&N RT patients, as a spray, or mouth wash/swish/gargle, prior to each radiation dose. Apart from clinical need, this choice was driven by the availability of a suitable pre- clinical model, in which the radiobiological model is radiation-induced ulceration of mouse tongue (1). The compound family can be described as DNA- binding antioxidants, the first lead compound being methylproamine (2). The mechanism of radioprotec- tion involves charge transfer along DNA, between a transient radiation-induced oxidising species (such as a Guanine radical cation) and the reducing radiopro- tector molecule bound in the minor groove (3). By analogy, the radioprotector acts like a “sacrificial anode” diverting the transient radiation-induced damage from DNA to the ligand, which presumably then dissociates from the DNA. The oral mucosa includes a barrier to drug penetra- tion, not unlike the stratum corneum, and thus has necessitated the design of molecules that can pene- trate the barrier to enable topical delivery to stem cells in the basal layer of the mucosa. Fortunately, since all the drugs are fluorescent, delivery to basal cell nuclei can be monitored by fluorescence micros- copy. Materials and Methods: A library of >200 new compounds with a characteristic bisbenzimidazole scaffold exemplified by a minor-groove binders Hoechst 33342 and methylproamine, have been syn- thesised and characterised by standard methods (2). Each compound was evaluated using an in vitro clonogenic survival assay that assesses both radio- protection and cytotoxicity. To assess topical delivery, drug formulation was ap- plied to the ventral surface of mouse tongue, and at various times after application, cryostat sections were taken for fluorescence microscopy. The radiobiological model involved irradiation with 25 keV X-rays of a 3mm x 3mm field on the ventral surface of mouse tongue, and monitoring of ulcers which appeared about 10 days after irradiation. For the fractionated version of the model, mice were ex- posed to daily snout irradiations with 160 keV X- rays prior to a single top-up/boost to the tongue, as for the single-fraction model. Results: A clinical candidate emerged from screening for radioprotective activity and cytotoxici- ty using the in vitro clonogenic survival assays, and evaluation of topical delivery. Proof-of-principal of topical radioprotection has been established in a mouse tongue model, for both single- fraction and fractionated irradiation. The extent of radioprotection (a Dose Reduction Factor of > 1.2) is such that based on a low-power retrospective clinical study, Grade-2 oral mucositis would be reduced to Grade 0/1. Discussion and Conclusions: A clinical trial is planned, but compound manufacture and toxicology remain as pre-requisite milestones. All 3 members of the compound family evaluated in the Ames test have proved negative, but a broad toxicology profile is a priority. However there are grounds for opti- mism. Under a Licensing Agreement (LA) to Or- thoBiotech (a J&J subsidiary) during 1999-2001, the licensee commissioned toxicology studies on the then lead compound (methylproamine), and the re- sults satisfied their requirements to proceed with the LA. Nevertheless, a new sponsor needs to be identi- fied to progress to clinical studies. References: 1. A. Gehrisch A & W. Dörr W. Strahlenther Onkol. 183:36-42 (2007). 2. R. F. Martin et al, Cancer Res. 64:1067-70 (2004) 3. R.F Martin & R. F. Anderson Int. J. Radiat. On- col. Biol. Phys., 42: 827-831 (1998). Tuesday 6th of February 09:35 DEVELOPMENT OF TRACK STRUCTURE MODELS IN GEANT4 FOR NANO-METER SCALE GOLD D. Sakata1,2,3, I. Kyriakou4, S. Okada5, H. N. Tran6, N. Lampe2, S. Guatelli1, M.C. Bordage7,8, V. N. Ivanchenko9,10, K. Murakami11, T. Sasaki11, D. Emfietzoglou4 and S. Incerti2,3 1 University of Wollongong, Centre For Medical Radiation Physics, Wollongong, Australia 2 Univ. Bordeaux, CENBG, UMR 5797, Gradignan, France, dousatsu-univtky@umin.ac.jp 3 CNRS, IN2P3, CENBG, UMR 5797, Gradignan, France 4 University of Ioannina Medical School, Medical Physics Laboratory, 45110, Ioannina, Greece 5 Kobe University, Organization for Advanced and Integrated research, Kobe, Japan 6 Irfu, CEA, Universite Paris-Saclay, Gif-sur-Yvette, France
 7 INSERM, UMR1037 CRCT, Toulouse France 8 Universite Toulouse III-Paul Sabatier, UMR1037 CRCT, Toulouse, France 9 Geant4 Associates International Ltd, Hebden Bridge, United Kingdom 10 Tomsk State University, Tomsk, Russia 11 KEK, Tsukuba, Japan Introduction: Gold NanoParticles (GNPs) are known to boost the effectiveness of photon based radiation treatments by increasing the absorbed dose in their vicinity. To investigate the effectiveness of GNPs, previous Monte Carlo simulation studies have explored GNP dose enhancement using mostly con- densed history models. However, in general, such models are suitable for macroscopic volumes and for electron energies above a few hundreds electron volts. We have recently developed, for the Geant4- DNA extension of the Geant4 Monte Carlo simula- tion toolkit, discrete physics models for electron transport in gold [1]. In this talk, we show the impact of new discrete physics models in microscopic gold volume. Materials and Methods: In this work, the new physics models are compared to the Geant4 Penelope and Livermore condensed history models, which are currently used for NP radioenhancement Geant4- based studies. Within this study, an ad-hoc Geant4 simulation application has been developed to calcu- late the absorbed dose in liquid water around a GNP and its radioenhancement, caused by secondary par- ticles emitted from the GNP itself, when irradiated with a monoenergetic electron beam. The effect of the new physics models is also quantified in the cal- culation of secondary particle spectra, when originat- ing in the GNP and when exiting from it. Results: The new physics models show similar backscattering coefficients with Livermore and Pe- nelope models in large volumes for 100 keV incident electrons. However, in submicron sized volumes, only the new physics models describe the high backscattering that should still be present around GNPs at these length scales. We found that the new physics models could be applicable to microscopic gold volumes down to 20 nm diameter at least. Figure 1. Two dimensional absorbed dose by secondary particles around GNPs irradiated by 100 keV monoenergetic electrons, in a 1 nm thick sampling plane. Left: Geant4_DNA_AU, Right: Liv- ermore in Geant4. Conclusions: Improved physics models for gold are necessary to better model the impact of GNPs in radiotherapy via Monte Carlo simulations. We con- cluded that the implemented discrete physics models are characterised by an improved performance for particle transport simulations in gold volumes with submicron dimensions. Acknowledgements: This work is funded by the University of Bordeaux, via the 2015 international post-doctoral fellowship program, for the “Nano- Boost” project. The work is also supported by the “France- Japan Particle Physics Laboratory (FJPPL)” international associated laboratory (CNRS/KEK) and by the Greece-France “Projet International de Coop- eration Scientifique (PICS)” #7340. This work is also supported by the Australian Research Council, ARC DP, DP170100967. References: 5. Dousatsu Sakata et al, “An implementation of dis- crete electron transport models for gold in the Geant4 simulation toolkit“, J. Appl. Phys. 120, 244901 (2016) Tuesday 6th of February 11:00 NANOTHERANOSTIC RADIO-ENHANCEMENT H L Byrne1, A McNamara2, F Lux3, G le Duc4, O Tillement3, R Berbeco5, Z Kuncic1 1 School of Physics, University of Sydney, NSW 2006, Australia hilary.byrne@sydney.edu.au 2 Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA 3 ILM UMR 5306 CNRS, Claude Bernard-University, Lyon, FRA. 4 NH TherAguix, SAS, France; 5 Department of Radiation Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA Introduction: The ability to design and build functional nanoscale structures provides the tools for interaction with and manipulation of fundamental biological processes at the sub-cellular scale on which they operate. The field of radiotherapy has developed a body of knowledge of the micro- and nano-scale mechanisms of radiation damage, relating characteristic ionisation patterns to biological effectiveness. This knowledge can now be exploited to explain and optimise the experimentally observed enhancement of radiation damage by high atomic number nanoparticles [1]. Herold et al. first demonstrated increased effi- ciency of kilovoltage radiotherapy in combination with small gold particles in 2000 [2]. Nanoparticle radio-enhancement has since been demonstrated for a wide range of incident particle types and energies [3,4]. While much attention has been paid to date to radio-enhancement with gold nanoparticles, recent studies have begun to focus on other high atomic number elements, for example bismuth [5]. The choice of element does not greatly affect the physical mechanisms of dose enhancement, but does offer the possibility of tailoring the addition of diag- nostic or therapeutic function. For example, the in- corporation of gadolinium, a contrast agent for mag- netic resonance imaging (MRI), delivers diagnostic imaging and enhanced radiotherapy treatment in the same nanoparticle [6]. The recent emergence of MRI-guided radiotherapy affords the ideal platform for exploiting nanotheranostic radio-enhancement. Materials and Methods: Nanoparticle radio- enhancement can be investigated and understood on several different physical scales. At the macroscale, physical dosimetry of the na- noparticle radiation enhancement effect presents a challenge. Detectors must be able to record the en- hanced numbers of short range photo-electrons from low energy photons which can be absorbed by only thin films of shielding. At the nanoscale, biologically important locally inhomogeneous dose distributions are created by extremely short range of Auger electrons. Monte Carlo simulations (see figure 1) can be used to gain insights into the nanoscale physical phenomena at work in radio-enhancement that are otherwise diffi- cult to obtain experimentally. Results: Patterns of energy deposition on the na- noscale are linked to the biological effectiveness of radiation treatment. The presence of high atomic number nanoparticles gives rise to high dose gradi- ents near their surface, which can be related to tu- mour control probabilities through models such as the Local Effect Model. However, the biological effectiveness is dependent on the nanoparticles’ dis- tribution relative both to each other, to important sub-cellular structures, and within the target tissue. Figure 1. a) simulation geometry for macroscale dose enhance- ment b) sub-cellular ionisation distribution Conclusions: High atomic number nanoparticles hold great promise for enhancing radiotherapy, through both compounding the radiation damage caused within the target tumour and enhancing image contrast for tracking nanoparticle uptake and improv- ing radiotherapy targeting precision. The best clinical implementation of this emerging paradigm requires a deep understanding of the mechanisms at work to allow development of an optimal treatment. References: 1. Kuncic, Z. and Lacombe, S. Nanoparticle radio- enhancement: principles, progress and application to cancer treatment. Phys. Med. Biol. In press (2017) doi:10.1088/1361-6560/aa99ced 2. Herold, D. M. et al. Gold microspheres: a selective technique for producing biologically effective dose enhancement. Int J Radiat Biol 76, 1357 (2000). 3. Butterworth, K. T. et al. Physical basis and biolog- ical mechanisms of gold nanoparticle radiosensitiza- tion. Nanoscale 4, 4830 (2012). 4. Lacombe, S. et al. Particle therapy and nanomedi- cine: state of art and research perspectives. Cancer Nanotechnology 8, (2017). 5. Detappe, A. et al. Ultrasmall Silica-Based Bismuth Gadolinium Nanoparticles for Dual Magnetic Reso- nance–Computed Tomography Image Guided Radia- tion Therapy. Nano Lett. 17, 1733 (2017). 6. Sancey, L. et al. The use of theranostic gadolini- um-based nanoprobes to improve radiotherapy effi- cacy. BJR 87, 20140134 (2014). Tuesday 6th of February 11:15 MODELLING THE HIMAC BIO BEAMLINE IN GEANT4 FOR MICRODOSIMETRY APPLICATIONS D. Bolst1, L. T. Tran1, S. Guatelli1, N. Matsufuji2, A. B. Rosenfeld1 1 Centre for Medical Radiation Physics, University of Wollongong, Australia, db001@uowmail.edu.au 2 Research Centre for Charge Particle Therapy, National Institue of Radiological Scienc, Chiba, Japan Introduction: 12C therapy has had a growing in- terest thanks to its enhanced physical and biological dose properities, however, the 12C beam produces a complex radiation field and it is important to charac- terise and understand the field which is produced. Monte Carlo simulations provide an insight to the radiation field but need to be accurate, in this work the modelling of the bio beamline at the Heavy Ion Medical Accelerator (HIMAC) in Japan is described and validated against experimental data. Materials and Methods: The Bio Beamline is a passive beam and was modelled using the Monte Carlo toolkit Geant4 [1] version 10.2p2. The model- ling of the beam starts after the beam nozzle as a pencil beam with an energy of 290 MeV/u, the beam is then formed to a circular shape by a pair of wob- bler magnets, operated using the single wobbling method. After the wobbler the lateral dose uniformity is improved by passing through a scatterer, the con- tribution of neutrons present in the beam are then reduced by passing through a neutron shutter (vacu- um tube). For a spread out Bragg Peak (SOBP), after the neutron shutter the beam passes through an alu- minium ridge filter to form the SOBP. The beam is then shaped by an aluminium four leaf collimator (FLC) and a brass collimator. After being collimated the beam is either incident upon a phantom or a scor- ing plane to generate a phase space file. The physics models used in the simulation in- cluded the G4StandardOption3 for electromagnetic interactions, the Bincary Intranuclear Cascade (BIC) for hadronic fragmentation and the neutron High Precision (HP) model for neutron interaction up to 20 MeV. To validate the Geant4 application the lateral and depth dose profiles were compared to experimental measurements using an ionisation chamber. To in- vestigate whether simplifying the beamline by ex- cluding the wobbler magnets had a noticeable impact on the beam profile alternative methods were simu- lated including: passing the initial point beam with- out the wobbler being active, having a uniform 100 mm diameter circular beam generated and finally generating a cone beam. Results: The lateral dose comparison between the experiment and simulation can be seen in figure 1 for both a mono-energetic and a SOBP taken at iso-centre before the phantom with both the FLC and brass col- limator fully opened. Excellent agreement is observed between experiment and simulation for both beams. The simplified beam simulation methods were com- pared to the full wobbler setup for a collimated 100 × 100 mm2 field size. It was found that the cone beam provided good agreement with the full wobbler setup while both of the alternatives gave poor agreement. For the depth dose comparisons the mono- energetic beam was found to have a excellent agree- ment with experiment for all simulation methods. The SOBP depth dose is shown in figure 2 and had slightly less agreement with experiment than the mono- energetic beam with a slight over-response in the dose towards the end of the SOBP. Unlike with the mono- energetic beam the different simulation methods had a drastic impact on the depth dose distribution, with the point and circle beams producing a flatter response while the cone beam matched the full wobbler setup very well. Figure 1. Comparison of the lateral profile of the experiment and the simulation for a mono and SOBP. Figure 2. Comparison of the depth dose profile of the experiment and the simulation for a SOBP Conclusion: A Geant4 application modelling the Bio Beamline has been described and validated against experimental lateral and depth dose measure- ments for a mono-energetic and SOBP 12C beam. Ex- cellent agreement was observed between simulation and experiment for both lateral beam profiles and for the depth dose distribution. Simplifed simulation methods without the wobblers were compared and it was found that a cone beam gave good agreement for both lateral and depth dose profiles. References: 6. Geant4 Collaboration (S. Agosti- nelli et al.), Nucl. Instrum. Meth. Phys. Res. A 506, 250-303 (2003). Tuesday 6th of February 11:25 LATEST DEVELOPMENT AND APPLICATIONS OF THE CHINESE REFERENCE PHANTOMS Rui Qiu1,2,*, Zhen Wu3, Chunyan Li3, Li Ren1,2, Wenjing Wang1,2, Hongyu Zhu1,2, Mingliang Dai1,2, Yuxi Pan1,2, Ruiyao Ma1,2,An kang Hu1,2,Junli Li1,2 1 Department of Engineering Physics, Tsinghua University, Beijing, China 2 Key Laboratory of Particle & Radiation Imaging (Tsinghua University), Ministry of Education, Beijing, China 3 Nuctech Company Limited, Beijing, China * Corresponding author: qiurui@mail.tsinghua.edu.cn Abstract: The Chinese adult reference male (CRAM) and female (CRAF) phantoms have been developed in previous work. Latest development and applications of the Chinese reference phantoms are introduced in this paper. A Chinese male phantom library was con- structed with 7 different heights ranging from 155 cm to 185 cm and 12 phantoms with different total body masses in each height. Chinese pediatric ref- erence phantoms were constructed for 3 months, 1 year, 5 years, 10 years, and 15 years male and fe- male respectively based on the CT medical images of different ages. The heights of the six established phantoms were 62 cm, 77 cm, 110 cm, 139 cm, 168 cm and 158 cm, respectively, and the weights were 7 kg, 10 kg, 19 kg, 32 kg, 55 kg and 50 kg, com- plied with the reference value. Each mesh-type phantoms consists of 108 different tissues and or- gans, which includes all the radiation-sensitive or- gans. A set of three-dimensional detailed breast mod- els based on the realistic structures in the breast and the Chinese female breast parameters were built. A mathematical model was established and then con- verted to a voxel model. First the breast shape was built, and then it was divided into skin, adipose tissue region, and fibroglandular tissue region. De- tailed structures such as Cooper’s ligaments, in- traglandular fats, and ductal lobes were built in different regions. A mathematical model for human respiratory tract was first established based on the anatomic bronchial parameters of adult Chinese male. Then it was voxelized to build a numerical voxel model, and integrated into the CRAM. This model featured by consecutive 16-generation bronchial structures, could represent the structure of entire lung trachea and bronchus structure. A detailed eye model was built based on the characteristic anatomic parameters of the Chinese adult male. This eye model includes seven main structures, which are scleral, choroid, lens, iris, cornea, vitreous body and aqueous humor. The lens was divided into sensitive volume and insensitive volume based on different cell populations. The detailed eye model was incorporated into the con- verted polygon-mesh version of the CRAM_S. The phantoms were applied in radiation protec- tion, including dose estimation from external expo- sure and internal exposure, in normal situations and in accidental situations. Detailed dose distributions in radiation-sensitive organs can also be obtained. The phantoms were also applied in medical imag- ing field such as dose estimation in mammography and CT. A series of organ dose conversion coeffi- cients for dose estimation in CT scanning and X- Ray radiology were calculated with the Chinese adult and pediatric reference phantoms. A series of glandular tissue dose conversion coefficients for dose estimation in mammography were calculated with the 3D detailed breast models. These data will provide references for the revision of the national standard for the estimation of the examinee's organ doses generated by X-ray diagnosis in China. Key words: Chinese reference phantom; de- tailed organ model; Monte Carlo; radiation protec- tion; medical imaging Tuesday 6th of February 11:30 Synchrotron Radiation LOCALISED SYNCHROTRON RADIATION IN MICE INDUCES PERSISTENT SYSTEMIC GENOTOXIC EVENTS MEDIATED BY THE FUNCTIONAL IMMUNE SYSTEM. Jessica Ventura1,2, Pavel Lobachevsky1,3, Jason Palazzolo1, Helen Forrester4, Nicole Haynes1,3, Alesia Ivash- kevich5, Andrew W. Stevenson6,7, Christopher J. Hall7, Vassilis Gorgoulis8,9, John Hamilton3, Alexandros G. Georgakilas10, Carl N. Sprung4, Olga A. Martin1,3 (olga.martin@petermac.org). 1Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; 2Royal Women's Hospital, Melbourne, VIC, Australia; 3The University of Melbourne, Melbourne, VIC, Australia; 4Hudson Institute of Medical Research, Clayton, VIC, ia; 5Canberra Hospital, Garran, ACT, Australia; 6CSIRO, Clayton, VIC, Australia; 7Australian Synchrotron, Clayton, VIC, Australia; 8University of Athens, Athens, Greece; 9University of Manchester, Manchester Academic Health Science Centre, Manchester, UK; 10National Technical University of Athens, Athens, Greece. Introduction: The discovery of the radiation- induced bystander effect (RIBE) (1) has expanded knowledge of radiobiological mechanisms beyond the scope of the central dogma of radiation biology, i.e. that only cells that absorbed a dose of ionising radiation (IR) are affected and the response is dose- dependent. The RIBE is now a well-established phe- nomenon comprising cyto- and genotoxic effects in out-of-field cells associated with irradiated cells. A counterpart in vivo phenomenon, a change in an or- gan or tissue distant from the irradiated region, was termed the radiation-induced abscopal effect (RIAE) (2). The mechanisms of the RIAE are only beginning to be understood, however the immune system has been proposed as the main mediator. It is not known how radiation settings affect non- targeted normal tissues and therefore the risk of radi- ation-related adverse abscopal effects. At the Imag- ing and Medical Beamline (IMBL), the Australian Synchrotron, we examined systemic effects of mi- crobeam radiotherapy (MRT) and broad beam (BB) configurations, in mice that were locally exposed to a very short pulse of a high dose-rate synchrotron beam (49 Gy/sec). We determined how radiation volume and dose impact the RIAE. We associated the propagation of these systemic effects with the induction of innate and adaptive immune effector responses and with modulations of plasma cytokine concentrations. Finally, we compared the RIAE in mice with the functional immune system and in im- mune-deficient mice. Materils and Methods: C57BL/6 mice were irradi- ated with 10 or 40 Gy incident dose of MRT or BB in an 8x8, 8x1, or 2x2-mm area of the right hind leg For irradiation with MRT, a collimator produced beam widths of 25 µm and microbeam centre-to- centre spacings of 200 µm. The absorbed doses of incident and scattered radiation were measured with the radiochromic EBT3 and XRQA2 films. Blood samples, irradiated skin and a variety of normal unir- radiated tissues were collected for DNA damage analysis of double-strand breaks (DSBs) quantified as γ-H2AX foci in tissue sections and oxidatitive clustered DNA leasions (OCDL) measured by con- stant field gel electrophoresis of genomic DNA treat- ed with pyrimidine- and abasic site-specific enzymes. We also measured the systemic immune response (plasma cytokine concentrations) and the local im- mune response (in-situ quantification of immune cells). The 10 Gy 8x8 mm MRT irradiation ex- perimet was repeated in immune-deficient mice; (i) NOD SCID gamma (NSG), (ii) CCL2/MCP1 knock- outs, and (iii) in C57BL/6 mice treated with anti- CSF1R ASF98 antibody which effectively depletes macrophages. Results: OCDLs elevated in a wide variety of unirradiated normal tissues. In out-of-field duode- num, a trend for elevated apoptotic cell death was observed under most irradiation conditions, however DSBs elevated only after exposure to lower doses (10 Gy peak dose, but not 40 Gy). These genotoxic events were accompanied by changes in concentra- tions of MDC, CCL2/MCP1, Eotaxin, IL-10, TIMP- 1, VEGF, TGFβ-1 and TGFβ-2 plasma cytokines and by changes in frequencies of macrophages, neutro- phils and T-lymphocytes in duodenum. Overall, sys- temic radiation responses were dose-independent (3). Strikingly, these effects and the abscopal innate and adaptive immune effector responses were completely or partially abrogated in the mice with various im- mune deficiencies, highlighting the role of the func- tional immune system in propagation of systemic genotoxic effects of localised irradiation. Conclusion: These findings have implications for the planning of therapeutic and diagnostic radiation treatment to reduce the risk of radiation-related ad- verse systemic effects. References: 1. KM Prise & JM O'Sullivan, Nature Reviews. Can- cer. 9:351-360 (2009). 2. S. Siva et al, Cancer Letters 356:82-90 (2015). 3. J. Ventura et al, Cancer Research, in press (2017 Tuesday 6th of February 12:05 TOWARDS IMAGE-GUIDED MICROBEAM RADIATION THERAPY E Engels1,2, S Corde1,2,3, M Westlake1,2, N Li1,2 , M Lerch1,2, , M Tehei1,2 1 Centre for Medical Radiation Physics (CMRP), Wollongong, NSW, Australia 2522, ee215@uowmail.edu.au 2 Illawarra Health and Medical Centre (IHMRI), Wollongong, NSW, Australia 2522 3 Prince of Wales Hospital, Randwick, Australia 2031 Introduction: Gliomas and glioblastomas are challenging tumours to treat due to their radio- resistance and residence in healthy brain tissue. In paediatric patients, conventional radiotherapy is of- ten implemented, but tends to provide only short- term benefits. Synchrotron generated, high dose and high flux microbeams are however better tolerated by normal tissue. Microbeam radiation therapy (MRT) imple- ments spatially fractionated, sub-millimetre x-rays to treat tumours, with great potential for successful gli- oma and CNS tumour therapy [1]. Nanoparticles are promising candidates for diag- nosis and radio-therapy. High-Z and paramagnetic nanoparticles not only improve the visibility of tu- mours for CT and MRI, but increase the dose con- formity to tumour tissue with clinical X-ray beams [2]. The ongoing use of paramagnetic gadolinium nanoparticles for MRI contrast has led to the removal of linear Gd products from the EU market due to toxicity concerns [3]. New metal oxide nanoparticles have properties that include lower toxicity, potential drug attachment, radiation enhancement and prefer- ential uptake into tumour cells [4,5]. This work examines the coupling of metal oxide nanoparticles with MRT, for better tumour control, less toxicity, and the capability of image-guided MRT with CT and MRI. Methods: To characterize the potential of metal oxide nanoparticles for MRT, Geant4 simulations were performed (version 10.1) to determine optimum conditions for nanoparticle-enhanced MRT. Ab- sorbed dose was measured in cell volumes and nano- particle enhancement expressed by Dose Enhance- ment Ratio (DER). Cell studies were performed with 9L gliosar- coma, grown in T12.5 flasks. Nanoparticles were sonicated and added 24 hours before MRT irradiation in hutch 2B at the IMBL, Australian Synchrotron. A pink beam spectrum with mean energy of 66 keV to optimise thulium oxide photon absorption (Figure 1) was produced by a 2T wiggler field. Surviving cell colonies were fixed and stained with crystal violet (30%) and ethanol (70%) and counted after 14 dou- bling times. Results: Nanoparticle-enhanced MRT was character- ised with Geant4 simulations. Higher energy mi- crobeams (above 90 keV) allowed a greater number of secondary electrons to extend the damage of a microbeam to the valley regions. Targeting the max- imum photon absorption of the nanoparticle led to localised and more selective damage. Figure 1. Comparing the Ratio of the mass energy absorption coefficient of Tm2O3 In vitro experiments confirmed that refining the beam energy selection, led to significant increases in MRT damage towards 9L tumour cells (Figure 2). Figure 2. MRT treatment of 9L gliosarcoma expressed as surviv- ing fraction with and without Tm nanoparticles. References: 1. Microbeam Radiation Therapy: Clinical Perspec- tives (Grotzer et al.) Phys Med 31, 564-567 (2015). 2. Nanoparticles in Cancer Imaging and Therapy, J Nanomater (Smith, et al.) Article ID 891318, 7 pages (2012). 3. European group recommends to stop using 4 line- ar GBCAs (Williams) Gadolinium Toxicity (2017). 4. Optimizing dose enhancement with Ta2O5 nano- particles for synchrotron microbeam activated radiation therapy. (Engels et al.) Phys Med 32 (12), 1852-1861 (2016). 5. Nanostructures, concentrations and energies: an ideal equation to extend therapeutic efficiency on radioresistant 9L tumor cells using Ta2O5 ce- ramic nanostructured particles. (Brown et al.) Bi- omed. Phys. Eng. Expres, 3(1), 015018 (2017) Tuesday 6th of February 12:20 FIBRE OPTIC DOSIMETRY IN SYNCHROTRON MICROBEAM RADIATION THERAPY James Archer1, Enbang Li1, Anatoly Rosenfeld1,2, Michael Lerch1,2 1 Centre for Medical Radiation Physics, University of Wollongong, NSW, Australia 2522, jarcher@uow.edu.au 2 Illawarra Health and Medical Research Institution. University of Wollongong, NSW, Australia, 2522 Introduction: Synchrotron microbeam radiation therapy is a novel pre-clinical therapy method that uses high brilliance, spatially fractionated, low energy synchrotron x-rays to deliver a very high dose rate within the microbeams. A conventional spatial frac- tionation for these beams is 50 μm microbeam width at 400 μm peak-to-peak separation. To perform do- simetry on these beams, a dosimeter with a high spa- tial resolution is required. We present a plastic scintil- lator fibre optic dosimeter that has been demonstrated to be able to resolve the microbeam structure. The advantages of such a dosimeter is the water equiva- lence, passive components exposed to the radiation field, relatively inexpensive components and simple fabrication. Materials and Methods: We use cylindrical BC- 400 plastic scintillator optically coupled to a 1 mm diameter core plastic optical fibre. BC-620 reflective paint was coated on the end of the probe to maximise the capture of light. A silicon photomultiplier (SensL MiniSM) was used to measure the light output of the probe. The use of plastic components ensures that the probe is water equivalent for radiation interaction. BC-400 is energy independent over a large range of energies, linear, and temperature independent over 0- 60 ˚C 1. The maximum one dimensional spatial reso- lution of the probe is determined by the thickness of scintillator used. We present the results from two probes, with 50 μm and 20 μm spatial resolutions, with measurements of the intrinsic microbeam profile, and depth dose curves. The experiments were performed at the Australian Synchrotron, on the Imaging and Medical Beam-Line. The 50 μm probe was tested using Gammex Solid Water to provide attenuation and back-scatter, while the 20 μm probe was tested in a water tank. To test the effect of the BC-620 paint on the light capture, the depth dose measurements with the 20 μm probe were repeated with and without the paint. Results: We were able to resolve microbeams with both resolution probes (shown for the 50 μm probe in Figure 1) 2. The average microbeam widths measured with the 50 μm probe was (63 ± 2) μm, which compares favourably with a silicon strip detec- tor of the same resolution (62.4 ± 0.9) μm. The 20 μm probe measured the widths to be (52.1 ± 6.5) μm. The depth dose measurements with the 50 μm probe matched that of a Pinpoint ionisation chamber except for an over-response at lower depth. This result was similar to the 20 μm probe in water. The effect of re- moving the BC-620 paint has no significant effect on the depth dose shape, but reduced the total light out- put by 24%. Figure 1. The intrinsic microbeam profile measured with the 50 μm resolution probe. Inset shows the centre section of the microbeam scan. Conclusions: The results presented here demon- strates the ability for the fibre optic dosimeter probe to be able to effectively resolve microbeams. The depth dose results show a consistent discrepancy to the ionisation chamber results at low depths. The comparison with and without the BC-620 paint demonstrates that any radiation hardening effects can- not explain this discrepancy. The higher sensitive volume of the ionisation chamber makes a direct comparison of the results challenging. The reduction in light output by removing the BC- 620 paint has two reasons; a lower amount of light being reflected back into the fibre, and the higher Z material of the paint (TiO2) having a higher dose en- hancement. As one of the main advantages of using a probe of this design is the water equivalence, not us- ing the BC-620 paint is justified to remove any possi- ble unwanted dose enhancements. Acknowledgements: This project was supported by UOW’s Global Challenges Program. This research was undertaken on the Imaging and Medical beamline at the Australian Synchrotron, Victoria, Australia (AS162/IMBL/10829). Authors JA, EL, AD, MC and ML acknowledge the support of the Australian NH&MRC (APP1093256). This research has been conducted with the support of the Australian Gov- ernment Research Training Program Scholarship. References: 1. Water-equivalent plastic scintillation detectors for high-energy beam dosimetry (A.S. Beddar et al.), Phys. Med. Biol. 37(10), 1883-1913 (1992). 2. X-ray microbeam measurements with a high resolu- tion scintillator fibre-optic dosimeter (J. Archer et al.), Sci. Rep., 7, 12450 (2017). Tuesday 6th of February 12:25 Space Dosimetry PROGRESS OF THE MICRODOSIMETRIC KINETIC MODEL IN HEAVY-ION RADIOTHERAPY Taku Inaniwa1 1 Department of Accelerator and Medical Physics, National Institute of Radiological Sciences, QST, 4-9-1 Ana- gawa, Inage-ku, Chiba 263-8555, Japan, inaniwa.taku@qst.go.jp Introduction: To date, more than 10,000 patients of vaious tumour sites have been treated with thera- peutic carbon-ion beams at the National Institute of Radiological Sciences (NIRS). In carbon-ion radio- therapy treatment planning, the biological effective- ness of the therapeutic beams have to be predicted based on one of biological models. The microdosi- metric kinetic (MK) model1,2 has been used for this purpose at the NIRS. For further development of heavy-ion radiotherapy, we started a research project of a hypo-fractionated multi-ion radiotherapy, name- ly a “quantum knife”. In the quantum knife, heavy ions up to neon are assumed as therapeutic ion spe- cies. Recent study revealed that the MK model may overestimate the biological effectiveness of heavy ions with linear energy transfer (LET) > 150 keV/μm, especially at high dose region.3 Thus, the MK model should be updated so that it is applicable in treatment planning of the quantum knife. In this study, a biological model, namely a stochastic mi- crodosimetric kinetic (SMK) model, will be reviewed and tested for in-vitro cell-survival fraction data. Materials and Methods: The ion-species de- pendences obserbed in the relation between LET and relative biological effectiveness (RBE) deduced from cell-survival data indicate that the LET is not an ideal index for expressing the biological effectiveness of heavy ions. Instead, microdosimetric quantities such as specific energy z may be better indices for this purpose, since they directly relate to ionizing density within microscopic sites. The microdosimetric kinet- ic (MK) model is one biological model used to pre- dict the cell-survival fraction from the specific ener- gy zd absorbed by a microscopic subnuclear structure “domain”.1 In the MK model, the survival fraction of cells S can be calculated by ( ) ( ) 2* d0ln DDzDS ββα −+−= (1) where α0 and β are cell-type specific parameters, and the variable zd * is the dose-averaged saturation- corrected specific energy absorbed by a domain. In the derivation of equation (1), the stochastic nature of the specific energy within the domain zd was considered, while that within the cell nucleus zn was neglected by assuming a constant value zn = D. Sato and Furusawa indicated that this approximation was valid only for radiations with LET < 150 keV/μm.3 They developed a computation method to numerically determine the cell-survival fractions by considering the stochastic natures of specific energies both in a domain zd and a cell nucleus zn, namely a stochastic mocrodosimetric kinetic (SMK) model. With the SMK model, the cell- survival fractions can be predicted accurately even for heavy ions with LET > 150 keV/μm. However, the computation based on the SMK model is too time- consuming to do in daily treatment planning especially with an iterative inverse planning. We updated the SMK model to be applicable in daily treatment plan- ning. The updated SMK model was tested to the in- vitro cell-survival data of HSG cells irradiated by he- lium, carbon, and neon ions.4 Results: Figure 1 shows the comparison between experimental and predicted cell-survival fractions of HSG cells irradiated by helium-, carbon-, and neon- ion beams at different LETs. The experimental data were reproduced by both the MK and the SMK mod- els for low LET radiations. However, for neon ions at LET = 654 keV/μm, only the SMK model reproduced the experimental data, and the MK model underesti- mated the cell-survival fractions. Conclusion: In this study, the SMK model was updated for a hypo-fractionated multi-ion radiothera- py, and was validated for helium-, carbon-, and neon- ion beams in wide LET and dose ranges. Figure 1. Experimental survival fractions of HSG cells irradiated by helium (A-C), carbon (D-F), and neon ions (G-I) compared with the predictions with the SMK (solid curves) and the MK models (dotted surves) References: 7. R. B. Hawkins, Radiat. Res. 140, 366-374 (1994). 2. T. Inaniwa et al., Phys. Med. Biol. 55, 6721-6737 (2010). 3. T. Sato and Y. Furusawa, Radiat. Res. 178, 341-356 (2012). 4. Y. Furusawa et al., Radiat. Res. 154, 485-496 (2000). Tuesday 6th of February 13:30 HIGH PRECISION TRACK GEOMETRY CALCULATION IN HYBRID-PIXEL DETECTORS Stuart P. George1*, Lawrence Pinsky1 1 University of Houston, Department of Physics, 3507 Cullen Blvd, Houston, TX 77204, USA * spgeorg4@central.uh.edu Introduction: Timepix Hybrid-pixel detectors are now being used for several applications in space and aerospace dosimetry by NASA and other organi- sations [1]. These include radiation monitoring on the International Space Station and the Orion space- craft, measurement of LET spectra as part of the Bio- sentinel satellite as well as flights on high altitude balloons and commercial aircraft. Hybrid pixel detectors consist of an array of sem- iconductor pixels coupled to an dedicated asic for readout. This means that hybrid pixel detector tech- nology acts like solid state nuclear emulsion and can provide detailed tracking information [2] for particles crossing the sensor such as the 600 MeV/A Silicon Ion shown in Figure 1. Figure 1, Example 600 MeV/A Silicon ion at high polar angle measured with a Timepix detector, color scale denotes deposited charge. This information can be used for particle charge and energy identification, especially when a particle has a long track extending over many pixels. Calcu- lating charge and energy is important both for vali- dating radiation transport models and calculation of the NASA 2012 radiation quality factors which are functions of charge and energy. Highly important to these calculations are precise measurements of the particle LET or stopping power which is used to di- rectly infer the possible energies and charge of any given track. The LET is calculated by measuring both the length and the deposited energy in the track. While quite some work has been done on improving the measurement of deposited energy [3,4] in the Timepix, the same effort has not been duplicated for high precision measurements of track geometry, es- pecially for longer tracks. This talk provides an overview of the current ‘state of the art’ for track LET measurement with hybrid pixel detectors, discusses some of the pitfalls in calculating track lengths and presents a novel methodology for accurately calculating the track ge- ometry. This is done by calculating the ‘length’ and ‘width’ of the track by building histograms along and perpendicular to the central line of the track. An em- pirical formula for calculating the track length from these quantities is derived based on a large dataset of different ion tracks gathered at the HIMAC facility in Chiba, Japan. This new procedure results in more accurate track length calculation as shown in figure 2. This in turn leads to more accurate LET distribu- tions which are verified by comparison to both theo- retical Landau-Vavilov distributions as well as Geant4 Monte Carlo calculations. This method is shown to work well for a wide variety of different ions. Finally we show how this improved LET calcu- lation also improves the calculation of other quanti- ties such as the reconstructed track energy. Figure 2. Plot showing measured track length distributions using the new (black), and old (red) calculation methods, compared to Geant4 Monte Carlo simulations (blue). References: 8. N. Stoffle et al, Timepix based radiation environ- ment monitor measurements aboard the interna- tional space station Nucl. Instrum. Meth. Phys. Res. A 762, 143-148 (2015) 9. S. Hoang et al, Data analysis of tracks of heavy ion particles in Timepix Detector J. Phys Conf Series 523, 1 (2014) 10. M. Kroupa et al, Energy resolution and power consumption of Timepix detector for different de- tector settings and saturation of front end elec- tronics J. Phys Conf Series 523, 1 (2014) 11. M. Kroupa et al, Techniques for precise energy calibration of particle detectors Rev. Sci. Inst 88 033301 (2017) Tuesday 6th of February 14:00 SIMULATION OF COSMIC RADIATION SPECTRA FOR PERSONAL MICRODOSIMETRY AT THE INTERNATIONAL SPACE STATION ALTITUDE S. Peracchi1, J. Vohradsky1, S. Guatelli1, L. T. Tran1, A. Rosenfeld1 1 Centre for Medical Radiation Physics, University of Wollongong, NSW, Australia 2522, sp009@uowmail.edu.au Introduction: Latest researches predict the cos- mic rays exposure during long space missions out- side the Earth’s geomagnetic sphere, as to the Moon and Mars, can double the cancer risk. The need to characterize cosmic radiation and its effects on astro- nauts’ health motivated the development of new sensible instruments capable to evaluate the dose at cellular level, strongly damaged by radiation. The Center for Medical Radiation Physics (CMRP) de- veloped a Silicon On Insulator (SOI) microdosimeter whose response needs to be studied in such mixed radiation field and whether its response can be used for biological risk prediction based on existing mod- els. Firstly, a detailed characterization of different ra- diation environment has been performed through Geant4 simulations. Material and Methods: The Low Earth Orbit (LEO) radiation environment, where the Internation- al Space Station (ISS) is currently orbiting, has been characterized through Geant4 simulations to obtain particles spectra inside and outside the ISS. We con- sidered different sources present in space as trapped protons and electron, Galactic Cosmic Ray (GCR) and Solar Particle Events (SPEs). They are mainly composed of protons, alpha particle and heavy ions with energy up to 100GeV/n. Our geometry is based on Columbus Module, as a component of ISS, represented by a multi-layer cyl- inder (1), surrounded by a sphere where particles are injected inward it with an isotropic distribution. Input spectra have been simulated in open Space at the altitude of ISS orbits with SPENVIS, an online tool to model space environment and its effects. The NASA