PET and multimodality imaging principles

• Dimitris VISVIKIS (INSERM)

History and physics of photon, electron, neutron and pion therapy

• Lembit SIHVER (TU Wien, Atominstitut)

Radiation Matter Interactions

• Gilles Ban (LPC Caen)

This lectrures aims to give an overview of the radiation matter interactions. Charged particles and neutral particles processes are described along with the main medical applications. (In the slides everything in light grey can be skiped, it contains material for a deeper understanding).

What is Medical Physics?

• Patrick Le Du

History and physics of ion beam therapy

• Lembit SIHVER (TU Wien, Atominstitut)

GATE lecture

• Maxime CHAUVIN (INSERM)

GATE exercise

• Maxime CHAUVIN (INSERM)

EasyPET exercise

• Martin Grossmann (Paul Scherrer Institut)

EasyPET is a table-top experimental kit to demonstrate the principle of PET imaging. After an introduction to the device and its components (scintillating crystals, silicon photomultipliers, coincidence electronics and reconstruction of PET images) we will explore the detector properties, study detector response from a beta plus emitter (radioactive source) and acquire a PET image

Radiotherapy / Organ motion lecture

• Ye ZHANG (PSI)

Image reconstruction exercise

• Trang Hoang Thi Kieu (HCMUS)

Opening Session

PET imaging in radiotherapy treatment planning

• Dimitris VISVIKIS (INSERM)

Research and development of CT, MRI, SPECT and PET images segmentation software for automatic detection and extraction of brain tumors using ITK, VTK, Qt

• Ho Thi THAO (Vietnam Acad. Science and Technology)

In the field of medical image processing, detection of brain tumor from computed tomography (CT) or magnetic resonance (MRI) scans is a difficult task due to complexity of the brain hence it is one of the top priority goals. In this work, we describe a new method which combines four different steps including smoothing, Sobel edge detection, connected component and finally region growing algorithms for locating and extracting the various lesions in the brain. The analysis results indicate that the proposed method automatically and efficiently detected the tumor region from the CT or MRI image of the brain. It is very clear for physicians to separate the abnormal from the normal surrounding tissue to get a real identification of related area; improving quality and accuracy of diagnosis, which would help to increase success possibility by early detection of tumor as well as reducing surgical planning time. This is an important step in calculating the correct dose of radiation therapy later. The computational algorithm proposed method was implemented using POCTA - a new software combining 3 tools: Insight Toolkit (ITK) to process input image, Visualization Toolkit (VTK) to display and Qt software development framework to build user interface

Quantitative CT imaging for airway structure and lung function

• Hyun Bin CHO (1School of Mechanical Engineering, Kyungpook National University, Daegu, South Korea)

Aim Using a recently developed quantitative computed tomography (QCT), this study explored segmental and parenchymal features of cement dust exposed (DE) subjects vs. non-dust exposed (NDE) subjects. Methods We employed 58 DE (Kangwon National University Hospital, KNUH) and 142 NDE subjects (Chonbuk National University Hospital, CNUH). Segmental structural metrics of airway diameter, wall thickness, and bifurcation angle were extracted. We extracted parenchymal functional metrics including inspiratory capacity (IC), percent emphysema (Emph%), and percent functional small airway disease (fSAD%). Results Regarding segmental structural metrics, DE subjects had airway narrowing at the 2-5-th generation (p<0.001), wall thickening at the 2-5-th generation (p<0.001), and an increase of branching angle of the trachea (p<0.001), compared with NDE subjects. In parenchymal functional metrics, IC was not significantly different between DE and NDE subjects. Emph% of DE subjects was slightly larger than NDE subjects (p<0.01) but fSAD% was not significantly different between the two groups. Conclusions This study showed that DE subjects had significant structural changes in segmental regions rather than parenchymal regions. This may be associated with a larger size of cement particles than other particles such as smoking or yellow dust.

Early diagnosis of insulinoma using PET: from cell culture to (pre)-clinical in vivo imaging

• Frédéric BOISSON (IPHC)

Insulinoma is a rare, usually solitary and benign neuroendocrine tumor (NET). It is characterized by inappropriate and uncontrolled insulin production and secretion, with consequent glycopenic symptoms and potentially lethal hypoglycemia. Early detection of the tumor is crucial, allowing curative treatment by surgical enucleation. The localization of insulinoma remains challenging, and conventional PET imaging is the first method used for diagnostic investigation. Patient premedication with carbidopa seems to improve the accuracy of 6-18F-fluoro-3,4-dihydroxy-L-phenylalanine (18F-FDOPA) PET for insulinoma diagnosis. Carbidopa is capable of drastically reducing physiologic pancreatic uptake, with a consequent increase in the tumor-to-background ratio. However, no final consensus about the usefulness of carbidopa premedication before 18F-FDOPA PET in patients with hyperinsulinemic hypoglycemia has been reached because of the potential reduction of tumoral uptake intensity. The present study represents the first preclinical research study focused on insulinomas, with a potential impact on the diagnostic and therapeutic management of patients in clinical practice. First, we developed an insulinoma xenograft model in mice and managed to keep the animals all along the study, despite a relatively high mortality due to the high insulin production of tumors. Secondly, we assessed two different radio-labeled molecules, according to the biological pathways describing the tumor model. In vitro and in vivo experiment were conducted to investigate the tumor uptake of both O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) and carbidopa-assisted 18F-FDOPA radiotracers. Finally, dynamic 18F-FET and carbidopa-assisted 18F-FDOPA PET scans were performed on tumor-bearing nude mice after subcutaneous injection of tumor cells and on a 30-year-old man with type-1 multiple endocrine neoplasia and hyperinsulinemic hypoglycemia defined by a positive fasting test. Results showed structural analogies between 18F-FET and 18F-FDOPA as well as the limited pancreatic uptake of 18F-FET in human, which suggests evaluating 18F-FET as diagnostic radiotracer for insulinoma detection in further prospective studies involving large cohorts of patients. This research work illustrates the multidisciplinary aspect of medical physics, which involves physics, chemistry and biology to answer a medical question. A specific focus will be put on infrastructures, instrumentations and methodologies which enabled this study.

Range verification in proton therapy: the LAPD demonstrator and its originalapproach to in-beam PET ballistic control

• Emmanuel BUSATO (LPC, Clermont)

In this presentation, original results obtained with the Large Area Pixelized Detector (LAPD) for in-beam ballistic control of hadrontherapy treatments are described. The LAPD system is a PET-like demonstrator built in order to test the feasibility of monitoring in real time, during irradiation, the ion range in the patient through the measurement of the beam-induced beta+ activity distribution. It has been designed with the aim of testing a few new and original solutions to overcome some of the in-beam PET challenges. These solutions are presented and their performances evaluated with data acquired with the 65 MeV proton beam of the Nice (France) protontherapy center are discussed. In particular, it is shown that the LAPD allows to monitor and detect in real time shifts of 1 mm in Bragg peak position in polymethyl methacrylate targets. Then, data to Monte Carlo simulation comparisons are presented and the performances on simulation of the activity profile reconstruction algorithm are described. The new high bandwidth LAPD data acquisition system will also be briefly discussed.

SBRT portal dosimetry based on Monte Carlo simulation

• A. Rita Barbeiro (INSERM)

Stereotactic radiation body therapy (SBRT) treatments require the implementation of robust pre-treatment and in-vivo dosimetry methods, to which electronic portal imaging devices (EPIDs) offer an attractive solution. However the development of EPID-based dosimetry models adapted to complex SBRT conditions is still challenging and is not completely supported for some EPID models and by commercial solutions. Therefore, in this work a detailed Monte Carlo (MC) model of the linac in combination with EPID is purposed to accurately predict the absorbed dose to the detector for further SBRT in vivo dosimetry applications. The MC simulation platform GATE/Geant4, was used to simulate the radiation transport through the detailed geometry of a previous validated model of a Varian TrueBeam STx, where the geometry of the aS1000 EPID was also implemented. Varian phase-space source files (PSFs) were used to simulate 6 MV FFF photon beams and to obtain secondary PSFs at linac exit and EPID scintillator layer, in which absorbed dose was calculated for field sizes ranging from 0.5x0.5 to 15x15cm2, and for a complete dynamic SBRT treatment. Corresponding EPID images were acquired in integrated and continuous modes, at 150 cm distance from the source and were compared to the MC calculated ones by means of relative dose difference maps and dose profiles, and global gamma index for the whole treatment. Results showed the suitability of the MC model in predicting EPID response for non-transit dosimetry with integrated images for simple fields and also dynamic SBRT treatments with continuous EPID imaging. However, in the latter, important discrepancies were still observed, mainly for points located at zones of higher dose gradients. This could also be related to the differences found between planned and delivered treatment parameters, and should be considered to improve simulation results and for further SBRT EPID in vivo dosimetry.

SIMULATION Simulation of I-131 radiopharmaceutical of thyroid cancer

• Nguyen Tat THANG (Hanoi Univ. Science and Technology (HUST))

I-131 is utilized for thyroid radiotherapy by giving radioactive I-131 in thyroid gland. As it involves ionizing radiation, it is important to ensure that the patients receive optimum amount of radiation to destruct the target tissue while keeping the radiation-related side effects to minimum. In clinical practice, standard activity doses are preferred for thyroid cancer patients, assuming that biokinetics are similar in all patients. Lately, many clinicians offered to individualize the radioactive iodine therapy by calculating the optimal amount of radioactivity using patient dosimetry. Radiation dosimetry is used to calculate the minimum effective and maximum tolerated absorbed dose for a successful radioactive iodine therapy. This approach enables to administer increased amount of therapeutic activity while minimizing the related side effects. In this study, the SAF values in critical organs were calculated using mesh-type adult ICRP phantoms to evaluate the risk of treatment. The results were compared with those of previous researchs based on others phantoms and thermoluminescent dosimeter.

Using the Geant4-DNA toolkit for estimating RBE of diverse radiation qualities

• Mario BERNAL (State University of Campinas)

Ionizing radiation can induce damage in the DNA of living beings. This damage can be repair by the cell but sometimes this does not happen so the functioning of the cell is altered, leading to cell death or cancer. This problem is of primordial importance in areas such as radiation therapy of cancer, radiation protection, and aerospace industry. The Monte Carlo (MC) method have the ability to simulate the transport of ionizing particles through matter. We have developed a biophysical model based in the combination of MC simulations, a DNA geometrical model with atomic resolution, and a methodology for linking the energy deposition process to the DNA damage. This model has been successfully applied for estimating the relative biological effectiveness (RBE) of different primary radiation qualities, including low energy photons, energetic ions, and fast neutrons. Results of some recent studies will be presented.

Simulation of liver cancer treatment using 90Y microspheres based on anatomical image segmentation technique and Geant4 toolkit

• Nguyen Hong HA (Vietnam Acad. Science and Technology)

The 90Y is a type of therapeutic isotope which have maximum beta energy of 2.23 MeV, the penetration in tissues about 1.1 cm and its half-life of 64.1 hours. Therefore, it is widely used in brachytherapy, especially in the hepatocellular carcinoma and other liver cancers. The quality of the treatment depends largely on the dose calculation in regimen planning. There are some dose calculation methods: (I) Body Surface Area method (BSA), (II) Empiric method, and (III) Partition method. All of these method are analytic or empiric methods. There have been some studies showing the limitations in accuracy of these methods. This study would present an approach to calculate dose in treatment planning. By using anatomical segmentation techniques to define geometry of liver and tumor for construct the simulation geometry. Besides, the distribution of 90Y in the liver also determined by this method. The material of liver/tumor is determined via CT number-densities based on Hounsfield scale. We are developing several semi-empirical models and implement to the Geant4 toolkit to simulate the interaction of the electron with matter and deposited dose distribution in the patient liver.

Functions and Interfaces in Particle Therapy System Simulation Framework

• Tsukasa ASO (Toyama College)

The particle therapy system simulation framework (PTSIM) is a Geant4 based simulation for particle therapy, which simulates radiation transport in a treatment port consisting of a beam delivery system and a treatment head with patient geometry. It is used in proton and carbon therapy facilities for validating treatment plans and improving irradiation systems. Although the PTSIM supports event-level parallelism in multithread and distributed computing environments on CPU-based architecture, the dose calculation under clinical treatment parameters requires more than several hours. To overcome the problem, the MPEXS project has developed a GPU-based Monte Carlo simulation for electromagnetic process and recently extended it to the hadronic processes of protons (MPEXS-proton). It is capable of completing the dose calculation within a few minutes. However, validation of the simulation against the measurements in the treatment port requires additional efforts and time. On the other hand, since each particle therapy facility has a validated PTSIM simulator, PTSIM can be used to prepare the phase space data of the beam delivery system. Using that data, MPEXS-proton can perform the dose calculation of patient geometry. In this paper, we report on the overall functionality of PTSIM and interfaces of phase space data relevant to the MPEXS project.

DRecent development of solid state microdosimetry and its applications in particle therapy

• Thuy Linh TRAN (Centre for Medical Radiation Physics, University of Wollongong, Australia)

Particle therapy has many advantages over conventional photon therapy, particularly 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 protons and heavy ions depends largely on knowledge of the relative biological effectiveness (RBE) of the radiation produced by primary and secondary charged particles. The RBE prediction based on microdosimetric approach using the tissue equivalent proportional counter (TEPC) measurements in 12C therapy has been reported, however large size of commercial TEPC is averaging RBE which dramatically changes close to and in a distal part of the BP that may have clinical impact. Moreover, the TEPC cannot be used in current particle therapy technique using pencil beam scanning (PBS) delivery due to pile up problems associated with high dose rate in PBS. Based on many years of experience in development of silicon-on-insulator (SOI) microdosimeter, the Centre for Medical Radiation Physics, University of Wollongong, has successfully developed a microdosimetric probe which is based on a SOI microdosimeter with 3D micron sized sensitive volumes (SVs) mimicking dimensions of cells, known as the “Bridge” and “Mushroom” microdosimeters, to address the shortcomings of the TEPC [1, 2]. The silicon microdosimeters provide extremely high spatial resolution and were used to evaluate the RBE of 290 MeV/u 12C, 180 MeV/u 14N and 400 MeV/u 16O ions at Heavy Ion Medical Accelerator in Chiba (HIMAC), Japan [3] as well as to measure the microdosimetric distributions of a proton pencil-beam scanning (PBS) and passive scattering system at the Massachusetts General Hospital (MGH) Francis H. Burr Proton Beam Therapy Center, USA [4]. Preliminary cell survival experiments on proton therapy beam in conjunction with SOI microdosimetry demonstrated good correlation between cell survival based RBE and predicted RBE based on measured dose average lineal energy with developed probe and microdosimetric kinetic model (MKM). References: [1] Rosenfeld A. “Novel detectors for silicon based microdosimetry, their concepts and applications”, Nucl. Instrum. Methods., Phys. Res. A 809, 156–170, February 2016 [2] Linh T. Tran et. al., “Thin Silicon Microdosimeter utilizing 3D MEMS Technology: Charge Collection Study and its application in mixed radiation fields”, IEEE Transactions on Nuclear Science, Volume: 65, Issue: 1, 467-472, Jan. 2018. [3] Linh T. Tran, et. al., “The relative biological effectiveness for carbon, nitrogen and oxygen ion beams using passive and scanning techniques evaluated with fully 3D silicon microdosimeters” Medical Physics, 2018 , DOI10.1002/mp.12874. [4] Linh T. Tran, et. al., “Characterisation of proton pencil-beam scanning using a high spatial resolution solid state microdosimeter”, Medical Physics, doi: 10.1002/mp.12563, 2017.

Preliminary Study for in-vivo dosimetry of the small animal irradiation

• Dong Wook KIM (Yonsei Cancer Center)

This study assessed applications for in-vivo dosimetry using a 3D printer-based, self-manufactured mouse immobilization device in a small field. The mouse immobilization device was created using a 3D printer (Makerbot Replicator, MakerBot Industries, Brooklyn, NY, USA) and consisted of the support flat, fixing units, sensor areas, and a build-up cap. Radio-photoluminescence glass dosimeters (RPLGD, GD-302M) were inserted at the upper left (UL), upper right (UR), lower left (LL), and lower right (LR) of the device at the center of the target. EBT3 film was inserted into the device at the top of the mouse’s head. Irradiation planning was performed using the ECLIPSE system after a CT simulation of mice with an immobilization device. The mice were irradiated 5 times at a dose 180 cGy with 6 MV X-rays. The dose measurements from the RPLGDs and films were compared with the doses calculated in the Eclipse system. The percentage differences between the Radiation Treatment Planning (RTP) System and RPLGD measurements were 5.56 ± 3.90%, 6.52 ± 5.32%, 10.0 ± 8.97%, and 15.9 ± 17.5% at the UL, UR, LL, and LR positions, respectively. The gamma passing rate of all film measurements exceeded 90% in the 2%/2 mm range. The error values of the 3rd measurements were outliers due to the set up. With the exception of the 3rd measurements, the percentage difference decreased to 4–7%. In this study, we evaluated the applicability of a mouse immobilization device in a small field. We performed in-vivo dosimetry using RPLGD and EBT3 film; this approach may be helpful for using radiation to accurately analyze results in animal studies.

Film Dosimetry in Radiotherapy

• Supriyanto ARDJO PAWIRO (Indonesia Univ.)

Detector for Dosimetry on LINAC and MedPhys education at CMRP

• Thuy Linh TRAN (Centre for Medical Radiation Physics, University of Wollongong, Australia)

An increase in the complexity of contemporary radiation oncology technologies demand sophisticated medical devices for verification of treatment delivery. The Centre for Medical Radiation Physics (CMRP) is an internationally recognised leader in the development of radiation detectors, providing real time high spatial and temporal resolution for treatment verification in radiation therapy. Pre-treatment and real time in-vivo treatment delivery verification in brachytherapy was resolved with the recently developed “Magic Phantom” and “BrachyView”. These systems allow fast verification of source dwelling and radioactive seed positions with submillimeter resolution for in-vivo real-time verification. Real-time motion adaptive radiotherapy aims to reduce the impact of patient-specific changes in anatomy during treatments through re-optimisation of the treatment delivery. Multi leave collimator (MLC) tracking utilises real-time tumour localisation to adjust the MLC configuration during delivery. Patient specific quality assurance of treatments employing MLC tracking is complex as daily variations in the patient’s tumour motion create new adaptations. We have developed a family of 2D high spatial and temporal resolution pixelated detectors (“Magic Plate”) to verify real-time motion adaptive radiotherapy delivery. The lecture will be devoted to present advances in medical dosimetry on LINAC, brachytherapy, interventional radiology using innovative semiconductor sensors. References M. Petasecca, M.K. Newall, J.T. Booth, et al “MagicPlate-512: a two dimensional silicon detector array for Quality Assurance of stereotactic motion adaptive radiotherapy” Med.Phys., 42(6) , 2992-3004, 2015 M. Safavi-Naeini, Z. Han, D. Cutajar, et al. ”BrachyView, A novel in-body imaging system for HDR prostate brachytherapy: Experimental evaluation”, Med Phys , 2015 Anatoly.B.Rosenfeld “Novel detectors for silicon based microdosimetry, their concepts and applications”, NIM A, 809, 156-170, 2016

OpenDose: a Free Online Database of Dosimetric Data for Nuclear Medicine

• Maxime CHAUVIN (INSERM)

Dosimetry in Nuclear Medicine uses a common formalism (MIRD) using pre-calculated reference Specific Absorbed Fractions and S Values. Such data is generated with Monte Carlo simulations for specific models and radioisotopes and is often computationally intensive. OpenDose is an international collaboration to generate, verify and disseminate reference dosimetric data. Using a common framework, every team provide reproducible data, with every value associated with uncertainty. The dosimetric data is then processed and stored in a SQL database and accessed through a newly created website. The website is designed to give the Nuclear Medicine community a free and easy access to dosimetric data.

PROTONS AND HADRONS History and Physics of Particle Therapy

• Lembit SIHVER (TU Wien, Atominstitut)

This lecture will present the history and physics of ion particle therapy, especially using protons and carbon ions. In 1946, Robert R. Wilson first proposed a possible therapeutic application of ion beams in his famous paper “Radiological Use of Fast Protons”. During the 50ths, in Berkeley (CA, US), the team of R. R. Wilson, John & Ernest Lawrence, and C. A. Tobias underlined the potential benefits of using heavy charged particles in radiotherapy. The pioneering work performed in Berkeley using p, d, 4He, 12C, 20Ne, 28Si and 40Ar during 1948-1992 will be discussed, and the first accelerator facility dedicated to carbon ion therapy, the Heavy Ion Heavy Ion Medical Accelerator in Chiba (HIMAC), will be described. The lecture will also give an update of all currently operating carbon ion facilities, and discuss the physical and radiobiological differences between photon, proton and carbon ion therapy. Especially the advantages of treating deep seated radioresistant hypoxic tumor cells with carbon ions will be discussed. The need for precise on-line range verification during ion therapy will be argued since range shifts might occur due to e.g. movements of the patient, movement of an organ, miss positioning of the patient, tumor shrinkage, filling of a cavity due to infections, etc. In the end there will be a summary and a future outlook.

Medical application of nuclear physics

• Taiga YAMAYA (QST Hospital International Therapy Research Center)

Current and future of independent dose calculation using Monte Carlo in Nagoya Proton Therapy Center

• Toshiyuki TOSHITO (Nagoya Proton Therapy Center)

More than two thousand patients have been treated by using proton beam at Nagoya Proton Therapy Center (NPTC) since 2013. The NPTC has both scanning and broad beam irradiation systems. Broad beam irradiation is mainly used to treat prostate and tumors with respiratory movements such as lung and liver, while scanning irradiation is mainly used for head and neck, bone and soft tissue, and pediatric cancer. The MC dose calculation for second dose check by using PTSIM which is a Geant4-based simulation framework for particle therapy has been carried out. It takes a half day to complete the MC dose calculation for one patient by using a CPU-based PC Linux cluster. In order to respond to more flexible changes in treatment plans, we plan to speed-up MC dose calculation by introducing a GPU-based Monte Carlo simulation system called MPEXS-proton, which is capable of electromagnetic and hadronic processes in Geant4 on CUDA framework. It will take less than a few minutes to complete the dose calculation for one patient. The MPEXS-proton system will be a promising device for dose calculation in proton therapy."

Progress in Proton Therapy Enabled by Technology

• Martin Grossmann (Paul Scherrer Institute)

Organ Motion and Image Guidance

• Ye ZHANG (PSI)

The design status of beamline system and gantry room of SC200 proton therapy

• Jinxing ZHENG (Chinese Acad. Sciences)

Controls for SC200

• Hansheng FENG (Chinese Acad. Sciences)

Carbon Fragmentation for Hadron Therapy

• Marc LABALME (LPCCaen)

Hadrontherapy treatments require a high accuracy on the dose deposition to keep the benefits of the precise ions ballistic. One of the sources of uncertainty on physical dose deposition is due to the fragmentation of the incident ion (fragmentation tails behind the tumor, RBE fluctuation in depth). Up to now, the simulation codes are not able to reproduce the fragmentation process with the precision required for treatments. The constraints on nuclear models and fragmentation cross sections in the energy range used in hadrontherapy are not yet sufficient. The maximum energy of GANIL, 95 MeV/u allows to constrain the low part of energies used for treatments. To improve the models and reach the precision required for a reference simulation code for hadrontherapy, experiments have been performed by our collaboration on thick target of medical interest in 2008, on thin targets at 95 MeV/u in 2011 and 2013 and at 50 MeV/u in 2015. The experimental set-up included five three stages ΔE-E telescopes composed of two Si detectors and one CsI scintillator. These telescopes were mounted on rotating stages to cover angles from 0 to 45°. Double differential cross section in energy and solid angle, of fragments resulting from nuclear reactions of 12C ions with PMMA and thin targets (C; CH2 ; Ti; Al; Al2O3) have been measured. The data of the experiments have already been analyzed and compared to GEANT4 simulations (BIC, jQMD, INCL++). The data have also been compared to codes included in PHITS (jQMD). Experimental results compared to GEANT4 and PHITS simulations of 50 and 95 MeV/u 12C cross sections on the different targets will be presented. We plan to do systematic measurements of fragmentation cross section of 12C on thin targets of medical interest for hadrontherapy (up to 400 MeV/u). A large acceptance mass spectrometer is under developpement. It will be composed of a beam monitor, a target, upand downstream trackers surrounding a magnet and a time-of-flight (ToF) wall. First beam tests of the beam monitor and the ToF wall will be performed at GANIL in june 2019. The FRACAS setup will be described.

Open Discussion: How to build and operate proton therapy center: Experiences for Vietnam

• Phan Viet CUONG

TPS Transition of dose calculation method in radiation therapy and the State of Art of treatment planning system

• Kenji HOTTA (Nat. Cancer Center Hospital )

In radiation therapy, simulation of dose distribution in the patient's body plays a major role in determining the quality of treatment. In the past, tissue inhomogeneity corrections for mega voltage photon beams could change the prescribed dose by 10% in lung cancer. The impact showed the importance of the dose calculation method. For the dose calculation in treatment planning systems, model-based algorithms have been used to shorten the calculation time. However, with the recent increase in calculation speed, accurate dose calculation algorithms such as the Boltzmann transport equation or the Monte Carlo method are spreading. Our facility also has implemented in-house Monte Carlo method for proton dose calculation. The in-house Monte-Carlo method reproduced measured dose distributions in a heterogeneous phantom better than the conventional pencil beam method. As a recent topic, biological effect prediction models are being introduced for treatment planning systems. This is an interesting area in the field of particle beam therapy, and a biological effect prediction model focusing on LET dependency has been developed. This talk reviews the transition of dose calculation method in radiation therapy and introduce the State of Art of treatment planning system.

Local Hypertermia

• Duong NHUNG (MEPI)

Hyperthermia (also known as thermotherapy) is generally regarded as a mean body or tumor tissue temperature higher than normal. The processing of increasing temperature is realized by three methods: local, regional and whole- body hyperthermia. Local hyperthermia has become a recognized and quite widespread adjuvant method of chemotherapy and / or radiation treatment of resistant tumors by using different techniques: Electromagnetic (EM) and Ultrasound wave that have reviewed. The technique selection depends on properties of tumors. The combination between method of local and radio/or chemo has applied successfully in the “N. N. Blokhin National Medical Research Centre of oncology” of the Health Ministry of Russia.

DETECTORS 18F-FDG autoradiography with CMOS sensor in murine models of lupus

• Nguyen Pham TRUONG GIANG (IPHC)

Nuclear imaging is essential in the clinical and pre-clinical field for studying the biodistribution of the drug and observing the evolution of the pathology. Positron Emission Tomography (PET) scan is today a gold standard with picomolar sensitivity for functional in vivo imaging. It offers millimeter-scale spatial resolution . Autoradiography, with Mimosa-28 semiconductor digital sensors, provides a sub-millimetre resolution while keeping a good sensitivity in order to visualize the cerebral distribution of the radiotracer 18F-FDG in the mouse. Preliminary, this sensor is characterized with isotope usually used in preclinical systems in the PET system: 18F. Measurements of efficiency and spatial resolution are made to compare with other current systems such as emulsion films, phosphorescence, scintillation and gaseous detectors. PET scans enable to explore biodistribution at the animal scale before to visualize the distribution with autoradiography at the tissue scale. We then explore the possibility of improving the quality of images through GEANT4 Application for Tomography Emission (GATE) Monte-Carlo simulation and reconstruction using a Maximum Likelihood Estimation Method (MLEM) algorithm. The autoradiographic images gain in contrast and the scattering of the charged particles into the medium is attenuated.

Characterization of EBT3 Films response to ionization radiations

• Charbel KOUMEIR (SUBATECH)

ARRONAX facility serves partially as a user facility for research. It hosts a multi-particle accelerator that can produce a wide quality of radiation (particle type and energy): protons from 17 MeV up to 70 MeV, and alpha-particles at a fixed energy of 68 MeV. ARRONAX proton beam is therefore adapted for preclinical research on cells or small animals. The beam, made of pulses delivered at a given frequency, can be produced with a large range of intensities from low (<1 pA) to high (up to 350 μA) intensities which means a large number of particles per pulse. Using a pulsing device such as the one developed at the ARRONAX facility, it is possible to precisely deliver the dose during a few μs (Flash irradiation) to a few minutes (conventional irradiation). Particular attention has been paid to the precise measurement of doses under different irradiation conditions, at the plateau of the Bragg curve (low LET), at the Bragg peak (high LET) and in function of the dose rate. The setting up of dosimetric detectors such as radiochromic films is necessary. Radiochromic films like Gafchromics EBT3 films (third generation) offer a high spatial resolution and have an effective atomic number close to the one of water. The active layer of the EBT3 films contains a form of colorless diacetylene long-chained monomers. Since the chains are aligned in ordered microcrystals they can form linear chained polymers with a carbon-backbone induced by ionizing radiation. Visible light is then absorbed by the backbone structure and the transparency of the film decreases. Due to polymerization reactions triggered by irradiation the film darkens with the blackening being directly related to the dose. Consequently it is then possible to calibrate the film response according to the delivered dose. The whole polymerization process can be assigned into different stages: physical, physico-chemical, and chemical which take place at different time scales of approximately between 10-17 sec and 1 sec throughout the whole process. Therefore, it is likely that under different irradiations conditions, with elevated dose rates or with high LET particle, the chemical reactions cannot be completed before another particle (primary or secondary) hits the same volume. As a result, the intermediate molecules could be altered and form different compounds due to newly formed radicals or reactive species. Consequently, the EBT3 films could react differently and their responses need to be studied. For that, several irradiations of the EBT3 films, under different conditions (high and low LETs, dose rate), have been conducted in collaboration with the Institut de Cancerologie de l’Ouest (ICO) and the Grand Accélerateur National des Ions lourds (GANIL). We will present the EBT3 films calibrations, the response studies in function of the irradiations parameters, as well as the assets of this dosimeter in the perspective of its use in hadrontherapy.

Ion beam monitoring using bremsstrahlung X-rays

• Flavien RALITE (SUBATECH)

Particle therapy provides a high and localized deposited dose to the target tumor thanks to the Bragg Peak. Then, the development of online beam monitoring tools with non-invasive methods represents an important challenge. Some studies deal with the use of prompt gamma radiations to localize the Bragg Peak, with a resolution of several millimeters. A novel promising approach using the detection of the bremsstrahlung X-rays is actually investigating, and requires improvements. Both methods have performance mainly limited by counting statistics and noise signal. These latter depend on the fundamental parameters such as cross sections. For that purpose, the work presented consists firstly to valid a theoretical model of the bremsstrahlung cross sections with experimental measurements. Secondly, the feasibility to use the bremsstrahlung X-rays coming from a PMMA target and a water tank, as a biological medium surrogate, in order to monitor proton beams was studying. An experimental set-up was designed to irradiate a PMMA target and a water tank with proton beams in the energy range from 17MeV/u to 50MeV, delivered by the ARRONAX cyclotron. A silicon drift detector measured the bremsstrahlung X-rays. A model based of the theoretical bremsstrahlung cross sections5 was developed to compare the experiment data to simulations. The differential cross sections were previously measured on carbon target to compare the results to data available in the literature6. Cross sections were measured in the range of 10 mbarn.keV-1 to 1000 mbarn.keV-1. A significate agreement was found with the model and the literature. Moreover, simulations fitted the bremsstrahlung spectra of the PMMA target confirming the significate sensibility of the method (104 X-rays/nC detected) and the validation of the ion bremsstrahlung model. Proton beam energy can be monitored using the bremsstrahlung X-rays thanks to the spectrum hardening, due to the variation of the bremsstrahlung cross sections. These results are encouraging in order to localized the proton beam range. Fundamental studies are also expected to link the bremsstrahlung signal to the deposited dose in the biological medium, in order to apply the method to dosimetry and medical applications

Development of a diamond hodoscope for online ion range monitoring in hadrontherapy

• Sébastien CURTONI (LPSC)

The ballistic property of ion beams is a key issue in hadrontherapy. Online ion range assessment during treatment would permit to fully exploit this advantage. In this context, Prompt-Gamma (PG) imaging using a Compton camera has been proposed by the French CLaRyS collaboration. The originality of the system is the use of a beam-tagging hodoscope that would provide temporal and spatial information on the incoming ions. This hodoscope at first relied on an array of scintillating fibres. To reach higher counting rate and a timing resolution of 100 ps, the collaboration has initiated recently the development of a diamond hodoscope. (CLaRyS Ultra Fast Timing). Diamond were selected for their very fast response and radiation hardness. Initially, for characterization purposes, pad detectors made of Chemical Vapor Deposition (CVD) single-crystal and polycrystalline diamonds as well as Diamonds grown On Iridium (DOI) were built. Then, to satisfy the position-sensitive criterion in the hodoscope prototyping, double-side stripped demonstrators were designed and assembled with custom discrete current preamplifiers at LPSC in Grenoble. Both pad and strip detectors have been characterized under various irradiation conditions. At GANIL, a 18 ps RMS Time-Of-Flight resolution has been obtained between a single-crystal and a DOI pad detectors with 95 MeV/u 12C ions. The same two detectors exhibit a 59 ps RMS Time-Of-Flight resolution when tested with 68 MeV protons in ARRONAX-Nantes. Single 68 MeV proton detection efficiency has been evaluated with two 1 cm² pad detectors: one polycrystalline and one DOI. The results are respectively 92% and 50%. Finally, stripped sensors were tested with a 8.5 keV pulsed X-Ray micro-beam at European Synchrotron Radiation Facility. A 100% detection efficiency and a 103 ps RMS time resolution were measured at several strips crossings with the polycrystalline sample. In conclusion, present results encourage, in a near future, the development of a larger area prototype made of four diamonds in a mosaic arrangement and read by a dedicated and integrated fast readout electronics currently developed at LPSC.

RT Screening method to follow up thyroid cancer patients after thyroidectomy

• Lembit SIHVER (TU Wien, Atominstitut)

This paper present a cost effective and simple screening method to follow up thyroid cancer patients who have had their thyroid surgically removed (thyroidectomy), without any metastases, and have been declared stable or cured. The method is based on using a small NaI (Tl) detector system and oral intake of 131I, to measure the concentrated radioactive iodine uptake (RAIU), together with measurements of levels of protein Thyroglobulin (Tg) in the blood. It is shown that measurements of RAIU together with Tg measurements can with high precision detect re-occurrence of thyroid cancer. Due to its simplicity and cost effectiveness, the presented method could be used at any local nuclear medicine department/medical center at the Vietnamese countryside, far away from the main hospitals. Then, if there are indications for a cancer re-occurrence, the patients could be sent to a major hospital to undergo a planar head and neck or full body single-photon emission computed tomography (SPECT) scan. If needed, follow up treatment with 131I could also be performed at the local nuclear medicine departments/medical centers. This would significantly reduce the costs for the patients and reduce the burden at the large/major hospitals.

Radiotherapy and Nuclear medicine in Kien Giang province: A review of current practice and future development

• Vu Ngoc TU

Radiotherapy and Nuclear medicine are particularly interested in Kien Giang, a southen province of Viet Nam. This paper provides several brief reviews about the development in Radiotherapy and Nuclear medicine in Kien Giang. In 2010, the first LINAC (Primus 5599) with four independent jaws was equiped. Hundreds of cancer patients were delivered by Primus 5599 each year with 3D-CRT and JO-IMRT techniques. The JO-IMRT technique has applied since 2016 for head and neck cases. Besides, a new modern LINAC (Clinac iX) with MLC-120 leaves has been installed in 2019 to perform high precise techniques such as IGRT and VMAT. To complete radiotherapy modality for cervical cancer patients, the Remote Afterloading Brachytherapy Unit has also been operated by using 192Ir isotope. Nuclear medicine specialty has been built recently that is related to the application of radioactive subtances in the diagnosis and treatment of disease. The Cyclotron 18MeV system will be operated to produce some radionuclides including 18F, 15O, 13N, 11C, and 124I. The QA/QC devices ,such as HPLC and HPGe, are equiped to assure the quality of produced radionuclides before injecting into patients. In addition, radiation detectors are placed at suitable location to keep safety all time. Nuclear medical images are required by PET-CT and SPECT (dual heads) units which were installed in 2017.

Fruit Party at the Beach

ISOTOPES Radio-isotope production at ELI-NP

• Andi Cucoanes (ELI-NP)

A proposition for a cancer treatment study using radioisotope metal cofactor enzymes

• Tran VAN LUYEN

Radionuclide spatial distribution measurement and dose deposition for in vitro assessments of targeted alpha therapy

• Anne-Marie FRELIN (GANIL)

Introduction. The interest of Targeted Alpha Therapy (TAT) for diffuse cancer or metastatic lesions is increasing because of the short range and the high linear energy transfer (LET) of α-particles. The development of new radiopharmaceuticals goes along with preclinical studies assessing their efficiency in tumor control as well as their toxicity on healthy tissues and comparing their effect with conventional external radiotherapy using x-rays or β-emitting targeted radiotherapy. It is thus necessary to determine the dose deposited in the sample (cells in the case of in vitro experiments) to accurately quantify biological effects. Nevertheless, dosimetry of α-emitters is challenging even for in vitro experiments. In this case, absorbed dose is related to the proportion of decay occurring close enough of the cells (because of the short range of α particles) and the cells dimensions (determining the proportion of energy deposited). It is usually assumed that the distribution of radionuclides in the culture medium is homogenous, which could have a significant impact on dose calculation. In this study we measured the spatial distribution of α-emitting 212Pb coupled to an anti-VCAM-1 antibody (212Pb-αVCAM-1) and its evolution over time in the context of in vitro irradiations. Methods. To determine the spatial distribution of 212Pb-αVCAM-1, two volumes of culture medium, containing 15 kBq of 212Pb-α-VCAM-1 each, were poured into two test wells without cells. The first well had a 2.5-µm-thick mylar-base and was placed above a 144 µm thick silicon detector. The second well was a commercially available dish and was placed below an identical detector. With these setups, experimental count rates and energy spectra of α-particles were measured during 20 hours. Experimental spectra were analyzed with Monte Carlo simulations. Experimental setups were reproduced to simulate the α-energy spectra in the silicon detectors as a function of the decay position in the culture medium. Simulated spectra were then used to deduce the radionuclide spatial and temporal distribution from experimental spectra. Results. Experimental count rates and energy spectra showed differences in measurements taken at the top and the bottom of dishes and temporal variations that did not follow 212Pb decay. The radionuclide spatial distribution was shown to be composed of a homogeneous distribution and concentration gradients at the top and the bottom, which were subjected to temporal variations caused by gravity and electrostatic attraction. The absorbed dose in cells calculated from this distribution was compared with the dose expected for a homogeneous and static distribution and found to be 1.75 times higher. This discrepancy is significant and is an important issue regarding the accuracy and the reliability of preclinical studies. Conclusion. This work demonstrated that accurate dosimetry of α-emitters requires the experimental determination of radionuclide spatial and temporal distribution. It highlighted that in vitro assessments of TAT cannot only rely on injected activity and should benefit from adapted dosimetry methods. Funding: CNRS, CEA, Université de Caen-Normandie, MESR, Conseil Régional-Normandie and the European Union-Fonds Européen de Développement Régional (FEDER), FRC, ANR-11-LABEX-0018-01 ; ANR-10EQPX1401.

Summary and conclusion

• Martin Grossmann (Paul Scherrer Institut)