WORKSHOP “PHYSICS FOR HEALTH IN EUROPE”
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Europe/Zurich
500/1-001 - Main Auditorium (CERN)
Description
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Speaker: Rolf Heuer (CERN Director General)
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Session 1: Radiobiology in therapy and space science 500/1-001 - Main Auditorium
Chair: Marco Durante (GSI and TU Darmstadt), Rapporteur: Bleddyn Jones (Univ.of Oxford)
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Early events in the formation of genetic damage by heavy ionsDouble-strand breaks (DBSs) are critical lesions and their spatial distribution is crucial regarding repair capability and biological effects. Ion irradiation leads to streaks of spatially localized damaged chromatin domains across cell nuclei revealed by repair protein immunostaining. Efficient repair after carbon ion irradiation is indicated by loss of the DSB marker H2AX, but repair is less pronounced with increasing ionizing density. Repair impairment after exposure to stopping carbon ions is the basis of the enhanced biological efficiency of heavy ion therapy. To study the effect of localized dose deposition on the early damage response, the recruitment of GFP-tagged repair proteins to ion-induced DSBs was monitored by live cell microscopy at the beam end. Recruitment times from seconds up to minutes were observed depending on the protein. The motional activity of DSBs was also analyzed in living cells up to 12 hours post irradiation. Superimposed to the fast Brownian motion, a slow mobility of damaged domains (mean square displacement about 0.6 µm²/h), most likely driven by normal chromatin diffusion, was observed independent of the radiation type. A (transient) formation of repair clusters could occasionally be observed, but long range displacements of DSBs did not generally occur. In conclusion, damaged chromatin shows a restricted mobility independent of lesion density and irradiation, supporting the notion that the spatial proximity of DNA breaks is required for the formation of radiation-induced chromosomal exchanges. Importantly, the processing of ion-induced DSBs is not coupled to an increased mobility enhancing the probability of translocations or cancer risk. These results offer important clues toward understanding the repair of multiple damage sites.Speaker: Dr Gisela Taucher-Scholz (GSI Biophysics, Darmstadt, Germany)
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The Space Radiation Environment - Constituents, Characteristics, and ModelsThe space radiation environment is a highly variable and dynamic one, with a number of constituent particle sources that need to be individually considered depending on the type of space mission planned. The Galactic Cosmic Rays form a slowly varying higher-energy background over the 11-year solar cycle, on top of which the sporadic, lower-energy, but essentially unpredictable Solar Particle Events with their proton emissions feature especially during the Solar Maximum periods. In the case of operations in Earth orbit, or for transits from the Earth to deep space, a degree of protection from these external charged particle sources is offered by the Earth's magnetic field, but on the other hand the Earth's trapped electron and proton radiation belts need to be considered. For large-scale space structures, such as the International Space Station or possible future Exploration missions, or for eventual lunar or planetary surface operations, the secondary particle background from Cosmic Ray fragmentation and neutron production is significant enough for it be taken into account in mission design as well as in operational planning. This presentation gives a summary overview of these various space radiation environment sources, together with a brief description of the different models available for their prediction. Some current ESA projects, observational activities and experimental results in this domain are also outlined.Speaker: Dr Petteri Nieminen (ESA)
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A proposal for an experimental facility at CERN for research in hadron-therapyThe feasibility is presented of setting-up an experimental facility at CERN, to be made available to European institutes, for research in radiobiology and dosimetry with light-ion beams, with minimum impact on CERN main activities. The possibility is first discussed of injecting and decelerating protons rather than antiprotons in the AD, providing beams with kinetic energies in the range 5–300 MeV. Proton beams were never decelerated in the AD in this energy range and this will require machine studies. The acceleration and extraction of 12C6+ ions is also in principle possible, but it will need a detailed study. A study of the production of carbon ions requiring a new ion source or development work on the present source is needed. A study will then be needed on the accelerator chain, Linac3, LEIR, PS and AD, to accelerate the carbon beam to the required energy range. Other possibilities involve providing carbon ions from LEIR or from the PS to an experimental facility in the East Area. A CERN involvement with hadron-therapy could be based on a three-stage scenario, short, medium and long term: 1) in a first phase (3 years) provide 100–300 MeV protons from the AD, offering beam time for the experiments in the range one to two months per year; 2) at the same time, carry out a detailed feasibility study for providing 100–400 MeV/u 12C6+ beams from either the PS or the AD, from the fourth year onwards; 3) assess the feasibility to set-up a dedicated experimental facility served by the AD – once the antiproton program has been terminated – to provide light ion beams (alpha particles to carbon or oxygen) from a few MeV/u to about 400 MeV/u. The intent of this talk is to stimulate discussion on the potential interest of setting up a European collaboration to fund the project.Speaker: Dr Marco Silari (CERN)
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Coffee Break and Poster Walk
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The Monte Carlo Code FLUKA in Ion Therapy: Status and OutlookBiological calculations in tumour therapy with ions depend on a precise description of the radiation field. In carbon ion irradiation, nuclear reactions cause a significant alteration of the radiation field. Therefore, the contribution of secondary fragments needs to be taken into account for accurate planning of the physical and biological dose delivery in the scheduled treatment. Treatment Planning Systems (TPS) for ion beam therapy essentially use analytical algorithms with input databases for the description of the ion interaction with matter. On the other hand, Monte Carlo (MC) codes with sophisticated nuclear models are more efficient (though slower) computational tools for handling the mixed radiation field. Therefore, MC codes can be very valuable tools to support ion therapy TPS. This contribution will address the application of the FLUKA MC code to ion beam therapy. Specific developments will be summarized. Comparisons with available experimental data and an overview of applications performed at several institutions (HIT, INFN, MGH etc.) will be given. These include calculations of physical and biological dose deposition in water as well as in tissue in comparison to analytical TPS, applications to Positron-Emission-Tomography, production of databases for new TPS and characterization of therapeutic beams. The results support the reliability of the FLUKA code for manifold treatment-planning related activities in ion therapy. However it is necessary to extend the collection of nucleus-nucleus cross-section data to better validate and eventually improve the models for specific and quite sensitive applications, like PET imaging, but also to provide a better description of mixed radiation fields for radiobiological calculations.Speaker: Dr Giuseppe Battistoni (INFN MILANO)
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Treatment plans in particle therapyA major issue of modern radiotherapy is the delivery of sufficiently high dose to the target, whereas the exposure of healthy tissue should be minimized. Swift light ions offer significant physical and radiobiological advantages compared to photon radiation. So far the technologically most advanced project to apply charged particles in radiotherapy was the GSI pilot project, now followed by the dedicated HIT facility. Ion beam radiotherapy requires sophisticated and efficient dose calculation and optimization procedures to obtain acceptable treatment plans. These aspects are integrated within our treatment planning system (TPS) TRiP98, clinically used in the pilot project, and further used as a research prototype. Since ab-initio calculations of radiobiological effects are neither reliable nor computationally feasible for years to come, we use the versatile Local Effect model (LEM) for the planning of all irradiations. Suitable approximations allow reasonably fast calculations of RBE-weighted dose even in complex configurations. Recent improvements for low-LET radiation, such as protons, will allow to compare plans with different ion-beam modalities under realistic conditions. Optimization of biological dose distributions is an important aspect of treatment planning. Simultaneous optimization of multiple fields under constraints results in enhanced target conformation and sparing of organs at risk. Future developments aim at "adaptive" treatment planning, i.e. dose painting and irradiation of hypoxic tumours. Considerable experimental efforts are necessary to validate the biological dose distributions predicted by the TPS. Unique devices like the Bio-phantom developed at GSI provide the means to measure one- and two-dimensional distributions of cell survival.Speaker: Dr Michael KRAEMER (GSI)
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The INFN Treatment Planning System ProjectSeveral technologies developed by the Italian institute of nuclear physics (INFN) for fundamental physics have been applied to medical imaging and particle therapy techniques. The partnership with leading industries has always been crucial for successful applications. Within this framework is the implementation of a Treatment Planning System (TPS) for hadrontherapy with C-ion beams, but not exclusively, in partnership with the IBA Group, with the contribution of the TPS manufacturer Elekta. Several INFN research groups that have developed competencies in different scientific areas are cooperating to the task: experimental and phenomenological nuclear physics, Monte Carlo (MC) and techniques for numerical analysis, radiobiology and hardware development for monitoring purposes. A TPS prototype is currently being studied. In order to achieve a fast plan optimization, the dose distribution is computed using look-up tables obtained from MC simulations. These are performed using Fluka and an implementation of the Local Effect Model (developed by the GSI Biophysics group). Nuclear fragmentation experiments for C-ion are now performed at the INFN's Laboratori Nazionali del Sud (LNS) (30-80 MeV/n). Further experiments are scheduled at SIS (GSI) in the framework of the FIRST experiment (200-400 MeV/n), in collaboration with other European Institutes (GSI, ESA, CEA). Radiobiological experiments are underway at LNS and Laboratori Nazionali di Legnaro, on rodent and human cells (C-ion @ 8-80 MeV/n). Lighter ions (A=6-12) will also be used, to reproduce the effects of fragments (up to 20 MeV/u). These experiments will provide reliable data for the validation of the simulations and for further improvements of the physical and radiobiological models to be used in the TPS.Speaker: Dr Andrea Attili (on behalf of the INFN-TPS collaboration)
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Syncrotron Radiation Therapy: a promising alternative to treat brain tumorsSynchrotron radiation (SR) therapy is a promising alternative to treat brain tumors, whose management is limited due to the high morbidity of the surrouding healthy tissues. Several approaches are being explored by using SR. The European Synchrotron Radiation Facility (ESRF) in Grenoble (France) has devoted one of its lines to biomedical research, highly focused nowadays to the development of new radiotherapy techniques. At the ESRF three techniques are under development: Stereotactic Synchrotron Radiation Therapy (SSRT), Microbeam Radiation Therapy (MRT) and, more recently, Minibeam Radiation Therapy (MBRT). Those radiation therapy programs are progressing rapidly towards the clinical trials with promising results for the treatment of high grade brain tumors. The preclinical studies on SSRT and MRT have shown promising results on healthy tissue sparing capability [1-4] and ablation of highly agressive tumor models [5-10], paving the way to clinical trials currently in preparation at the ESRF. With this aim, different dosimetric aspects from both theoretical and experimental points of view have been assessed in SSRT and MRT. In particular, the definition of safe irradiation protocols [11], the beam energy providing the best balance between tumor treatment and healthy tissue sparing in MRT [12] and MBRT [13], the special dosimetric considerations for small field dosimetry, etc will be described. In addition, for the clinical trials, the definition of appropiate dosimetry protocols for patients according to the well established European Medical Physics recommendations will be discussed. Finally, the state of art of MBRT developments at the ESRF will be presented. MBRT is the most recently radiotherapy technique implemented at the ESRF [14]. The main advantagSpeaker: Dr Yolanda Prezado (European synchrotron Radiation Facility)
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Discussion
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Introduction to poster session by chairmen
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Poster session
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19:30
Workshop Dinner in the Globe Globe 1st floor
Globe 1st floor
CERN
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Session 2: Radioisotopes in diagnostics and therapy 500/1-001 - Main Auditorium
Chair: Jean- Francois Chatal (ARRONAX), Rapporteur: Ulli Koester (ILL)
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Production of innovative radionuclides at ARRONAX and 211At RITARRONAX, acronym for "Accelerator for Research in Radiochemistry and Oncology at Nantes Atlantique", is a high energy and high intensity cyclotron. It will turn into operation in the beginning of 2010 in Nantes (France). It is mainly devoted to the production of radionuclides for medicine. A priority list based on the capability of the machine as well as on the need expressed by the European medical community through a questionnaire has been set.It contains isotopes for imaging (82Sr/82Rb and 68Ge/68Ga generators and 64Cu, 44Sc) and for therapeutic use (67Cu, 47Sc and 211At). Astatine is the heaviest radiohalogen and 211At is one of the most promising -emitters for medical applications. The half-life of 211At is relatively long compared with that of other radionuclides available for -RIT (T1/2 = 7,2 h). A large collaboration effort has been done in Nantes for many years both on the production and extraction of 211At and its labelling.The production will be done in ARRONAX using a 28 MeV alpha beam hitting a bismuth target evaporated under vaccum on AlN support. For recovery of astatine, two methods have been developped : liquid extraction and dry extraction. For labelling, a special attention has been focused on antibodies. Succinimidyl AstatoBenzoate (SAB) is used to bind 211At on the antibody by esterification of lysin residue. In vitro as well as in vivo stability have been tested on a murine model. An overall labelling yield of around 50 % was obtained.In the near future, ARRONAX will participate in a radioimmunotherapy collaborative project (Alpha-RIT) using 211At coupled to a specific antibody to treat patients with disseminated residual disease of prostate cancer. ARRONAX will have to produce large activities of 211At for phases I and II clinical studies.Speaker: Dr F. HADDAD (GIP ARRONAX and SUBATECH, Nantes)
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Tb-149 radio-immunotherapy - advances of short-range alpha radiation and 4.1 h half-life demonstrated in vitro and in vivoRadioimmunotherapy (RIT) of disseminated diseases in which individual cells or cell clusters are remaining requires a radionuclide that is capable of sterilizing individual cells with minimal radiotoxicity to surrounding healthy tissue. α particles exhibit high linear energy transfer and very short range in tissue, making them ideal for single-cell killing. 149Tb is a radiolanthanide that emits α particles with only 28 µm range in tissue. Feasibility and potential advantages of 149Tb over other radioisotopes in RIT have been studied in preclinical experiments using different monoclonal antibodies targeting leukemia, lymphoma and gastric cancer. 149Tb was produced at ISOLDE-CERN by on-line mass separation of spallation products released from a Ta target irradiated with 1 GeV protons. The monoclonal antibodies HuM195, Rituximab and d9ECad were conjugated with CHX-A-DTPA and labeled with 149Tb with specific activities of 0.1-1.1 GBq/mg. In vivo capability of treating disseminated cancer was investigated using a disseminated lymphoma mouse model. 149Tb RIT with 5.5 MBq labeled Rituximab 2 days after an intravenous graft of lymphoma cells resulted in tumor free survival for >120 days in 89% of treated animals. In contrast, all control mice developed lymphoma disease. There are many unsolved clinical situations in oncology, where α emitters are hoped to serve as therapeutic breakthrough to improve survival of cancer patients, e.g. disseminated single cell disease like leukemia, adjuvant treatment for circulating or loco-regionally remaining cells in solid tumors or treatment of minimal residual disease in lymphoma. Our experiments with 149Tb produced at CERN demonstrate this α emitter’s potential to overcome limitations of other radioisotopes in selected clinical settings.Speaker: Dr Matthias Miederer (Universitätsmedizin Mainz, Germany)
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Radiation Protection Aspects Related to Lutetium-177 Use in Hospitals177Lu is typically produced by direct irradiation with neutrons from enriched 176Lu. During direct irradiation of 176Lu remarkable amount of 177mLu (T1/2 = 160 d) is produced. The 177mLu content in the labelling solution is mainly depending from the two factors: irradiation time and how much time has passed after end of the irradiation. Typically carrier added (c.a.) 177Lu is produced in the irradiations positions, where neutron flux is 1 3*1014 neutrons cm-2 s-1 and irradiation time is 14 days. Reported values for 177mLu/177Lu ratio from several reactors varies between 0,01% - 0,02%. The hospitals are using their 177Lu up to one week after end of the irradiation when 177mLu/177Lu ratio has doubled. 177Lu is mainly used to peptide labelling. Typical dose is 7 – 9 GBq. If 177mLu/177Lu ratio is 0,02%, it means that a dose includes 1,4 – 1,8 MBq 177mLu. To handle radioactive materials, which are above free limit, it is required to have a radioactive material licence. For 177mLu free limit is 1 MBq, if free limit is exceeded the nuclide needs specific licence or licence as by product. Hospitals which are using over 5 GBq c.a. 177Lu should have radioactive licence also for 177mLu. During labelling process and treatment the loss of radioactivity is typically 2 to 5% of activity which is equal to 90 kBq 177mLu. The release limit is 10 Bq/g waste. All waste should be collected and shipped to radioactive deposit or let to be decayed. A patient is going to extract approximately 80% dose (1,45 MBq) through urine relative fast. The highest allowed radioactive concentration in the sewage water canal is 50 kBq/m3. It means that patient dose need to be diluted to 30 m3 after cooling time, which is required to 177Lu decay.Speaker: Dr Richard Henkelmann (Isotope Technologies Garching)
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Preclinical studies with non-standard and carrier-free radioisotopes from ISOLDE-CERNSystemic radionuclide therapy is a very challenging field of nuclear medicine. The search of new tracers that may become a radiopharmaceutical is driven mainly by disciplines as biochemistry, organic chemistry and coordination chemistry, while modern radiochemical or nuclear physics achievements are often not adequately included. Frequently the development of new radiopharmaceuticals is limited to the use of the rather small number of radionuclides that are commercially available. We will review a series of experiments that have been performed from 1975 to 2005 in an interdisciplinary collaboration between nuclear medical institutions, radiochemistry and CERN-ISOLDE. We will illustrate how present-day technology developed partially at CERN (high energy proton induced reactions combined with high-tech physico-chemical separation techniques) improves the quality and choice of radioisotopes enormously. These new high quality research radionuclides can significantly increase the efficiency in R&D towards improved systemic radionuclide therapies. The biological response as function of the individual radionuclide can be studied systematically with higher efficiency. The same concerns the relation between radiation energy and biological response for different lesion sizes. We will present results from particularly efficient simultaneous multi-isotope measurements of biodistributions of several chelates and conjugates of rare earth elements. We also show examples of innovative PET and SPECT isotopes that, since they exhibit the same biodistribution as the respective therapy isotope, may serve for personalized in-vivo dosimetry. In conclusion these experiments show the potential of introducing new commercially not available carrier-free radionuclides for diagnostics and therapy.Speaker: Gerd Beyer (Department of Radiology)
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Discussion on therapy including possible use of ISOLDE isotopes
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Coffee break and Poster Walk
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Panel discussion on 99mTc supply crisis and alternatives with short contributions followed by interactive discussion
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The Future for 99mTc and 99Mo in nuclear medicineThe Future for 99mTc and 99Mo in nuclear medicine 99mTc is an unusual radionuclide choice for imaging but has become the most frequently used radioisotope in nuclear medicine and has made single photon emission computed tomography (SPECT) an extremely powerful in-vivo diagnostic imaging tool. Recent advances in imaging camera technology offer a very promising future for this method of imaging but the supply of the radionuclide is now under threat. 99mTc is supplied to clinical users in the form of 99mTc/99Mo generators loaded with the parent 3 day half-life radionuclide 99Mo. 99Mo is produced by a complicated supply chain that relies on nuclear fission of 235U in nuclear research reactors. Most of these reactors are ageing and in 2010 there is just not enough of this specialised reactor capacity to meet all the world’s demand for 99Mo. There are existing reactors planning to start producing fission 99Mo and several alternative methods are being proposed, some of which require accelerators not reactors. Unfortunately some nuclear medicine scans are already being diverted to different imaging methods that do not rely on the supply of 99mTc. This paper will provide an industrial perspective on a situation which has been described as a ‘crisis’ for the nuclear medicine community. Reasons for selecting 99mTc and the latest instrumentation advances will be described, the clinical use of the different radionuclides will be summarised and current capacities of fission producers reviewed. The various alternative methods of producing 99Mo will be examined with a commentary of the technical and economic challenges facing each of the options. Finally the latest news from the fission ‘moly’ supplier industry will be made available.Speaker: Prof. Dewi M. Lewis (General Electric Healthcare)
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Feasibility study of an accelerator-driven production of Mo-99 for Tc-99m generators using a high-power LINACFeasibility study of an accelerator-driven production of Mo-99 for Tc-99m generators using a high-power LINAC A compact accelerator-driven neutron activator based on a modified version of the Adiabatic Resonance Crossing (ARC) concept, proposed by C. Rubbia and experimentally demonstrated at CERN in 1997, has been developed with the aim of efficiently exploiting ion-beam generated neutrons for the production of radioactive nanoparticles for brachytherapy using small/medium-size cyclotrons for medical applications. A prototype of the activator is currently operational in JRC-Ispra, coupled with a 40 MeV – 50 uA cyclotron, and a higher scale version, to be coupled with the 70 MeV-350 uA cyclotron of the Arronax centre in Nantes, is under design (THERANEAN project). The experimental results obtained with the JRC neutron activator prototype indicate the feasibility of a cyclotron-driven production of β- emitting radioisotopes for brachytherapy. The possibility to produce 99Mo through the 98Mo(n,)99Mo reaction induced by the neutrons generated using a high-energy (1 GeV)/high current (~1 mA) LINAC, and moderated/confined with an ARC-type activator has been also explored. Two Monte Carlo codes (FLUKA, MCNPX) have been used to simulate the system and carry out a preliminary optimization of the system parameters. Activation results and system potential productivity in different configurations were compared with available results on 99Mo production through 235U fission in nuclear reactor. The possibility of an accelerator-driven fission-based production in the activator was also examined. Results show that the total world demand could be potentially covered with the 98Mo(n,)99Mo production using a 1GeV-4 mA LINAC-driven neutron activator.Speaker: Mr luca maciocco (advanced accelerator applications)
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Gallium-68 – a candidate for use in clinical routineThe 68Ge/68Ga radionuclide generator (68Ge, T1/2 = 270.95 d) is an excellent cyclotron-independent source for the positron emitter 68Ga which is successfully used in clinical PET. Nevertheless there remain open problems in the routine use related to the applicability of the technique in clinical environment and legal aspects. An effective application of the generator produced 68Ga can be limited by poor chemical and pharmaceutical quality of the generator eluate. Thus traces of metals, as a consequence of the use of metal oxide based matrixes; rather large volume and high acidity lead to suboptimal conditions of the radiolabelling reaction and can decrease the reproducibility in the routine preparation of 68Ga-radiopharmaceuticals. In order to extend the shelf-life of the generator systems, high initial activities of the 68Ge are used. A long-term utilization of the generator systems in non-gmp environment can cause, however, decreasing of pharmaceutical quality and conflict with legal aspects of in-house radiopharmaceutical production. Finally, users face the problem of the generator utilization, since long-lived 68Ge can not be declared as decay waste. In this context we propose a novel “metal free” 68Ge/68Ga radionuclide generator system dedicated for production of high quality gmp grade 68Ga preparations. The concept includes an effective 68Ge management and improved logistic for the routine utilization of the radionuclide generator system in clinical environment.Speaker: Dr Mark Harfensteller (ITG Isotope Technologies Garching, Germany)
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Session 3: Prospects in medical imaging
Chair: Alberto del Guerra (INFN), Rapporteur: Wolfgang Enghardt (TU Dresden)
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Keynote:' Radiology meets Physics: the future of MRI'Speaker: D. Le Bihan (IFR Institute d' Imagerie Neurofonctionelle)
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Multimodality approach in the study of Tumor Angiogenesis: Magnetic Resonance Imaging (MRI), Synchrotron Radiation based micro-CT (SRμCT), Positron Emission Tomography (PET) and Histological Examination to follow the vessel formationSeveral imaging techniques are available to study the neovasculature during tumor angiogenesis. MRI provides information on morphology,blood volume (TBV),blood flow (TBF) and on the average vessel diameter (vessel size index,VSI),PET enables studies of metabolic activity. To visualize the 3D vessel architecture at a capillary level (5-10μm) SRμCT is needed.Validation of in vivo imaging data is achieved by comparison with histology. The aim of this work was to characterize vessel formation in tumors using multimodal imaging strategies in order to elucidate multiple aspects of the angiogenic process. Twelve balb/c nude mice were injected s.c. with 106 C51 cells (colon carcinoma). For a first validation study, anatomical images,TBV,TBF,VSI maps of 6 mice were recorded using MRI.The animals were sacrificed and the tumors explanted for SRμCT in phase-contrast and absorption modes. Thereafter a longitudinal MRI-PET study has been carried out using 6 mice. Measurements were performed every 3 days.PET protocol consists of the injection of 18F-MISO to visualize the hypoxic regions. Histological examination was performed on every tumor using the endothelial marker CD31,hypoxic marker pimonidazole and perfusion reporter Hoechst. The data were analyzed using the standard medical images approach and a novel method based on fractal analysis. The results display significant tissue heterogeneity in the growing tumor. Differences have been found with regard to morphological appearance, physiological behavior and degree of hypoxia. Images from SRμCT showed a chaotic structure of the vessel architecture. By using complementary imaging modalities it is possible to analyze various aspects of the vessel network formation in tumor tissue yielding interesting mechanistic insight.Speaker: Marco Dominietto (Institute for Biomedical Engineering - ETH and University Zurich)
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ClearPEM-Sonic: the combined positron emission mammograph and ultrasound elastography scannerBreast cancer is among the most frequent cancer types for women. The average life-time risk is about one eighth. As early detection leads to high cure rates, breast cancer screening is a priority in healthcare policies. However, conventional methods like X-ray mammography and echography show lesions but lack specificity. Additionally, those techniques are based on tissue density differences that complicate diagnosis in the case of dense breasts. It is thus important to provide additional means for early detection. The Crystal Clear Collaboration developed a positron emission tomograph for mammography, the ClearPEM. It is based on LYSO:Ce crystals read out on both sides with avalanche photodiodes. This allows measuring the depth of interaction in the crystals with a precision of 2 mm and contributes to good spatial resolution and high sensitivity. Trials on the prototype confirm a spatial resolution of 1.3 mm. For ClearPEM-Sonic, this performance is expected to improve as the light yield of the crystals has been increased by 20% whilst keeping the same depth of interaction and energy resolution. Yet, the main objective is to improve diagnosis by combining metabolic information from ClearPEM with morphological and anatomical information from a new-generation ultrasonic transducer that objectively quantifies tissue elasticity, developed by SuperSonic Imagine. The main challenge of combining both modalities is, aside from the mechanical integration, the fusion of both images to guarantee excellent mapping precision. This has been solved by immobilizing the breast and providing information about the position of both images in space via a combination of fiducial markers and high-precision positioning devices. ClearPEM-Sonic is a CERIMED project with CERN as a partner.Speaker: Mr Benjamin Frisch (CERN and Technische Universität Wien)
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LaBr3 and LYSO monolithic crystals coupled to photosensor arrays for TOF-PETPositron emission tomography (PET) detectors based on a monolithic scintillation crystal coupled to a photosensor array can maximize scanner sensitivity and allow excellent intrinsic spatial resolution as well as depth-of-interaction (DOI) correction. Investigating the suitability of such detectors for time-of-flight (TOF) PET, we are focusing on the promising combination of fast and bright LaBr3 and LYSO scintillation crystals with silicon photomultiplier (SiPM) light sensors that provide low noise, high gain and small transit-time jitter. In order to correct for the time walk as function of the 3D annihilation photon interaction location in the crystal, a maximum likelihood estimation algorithm to determine this location was developed. It was applied to a 20×20×12 mm3 LYSO:Ce crystal coupled to a fast 4×4 multianode photomultiplier (Hamamatsu H8711-03) and a bare 18.2×16×10 mm3 LaBr3:Ce(5%) crystal coupled to a Hamamatsu S11064-050P(X) 4×4 SiPM array. Throughout the LYSO crystal, the time walk spans a range of ~100 ps. Time walk calibration allows an event-by-event correction, resulting in an almost complete time walk cancellation. For the LaBr3 detector, time walk vs. DOI spanned only ~15 ps. For 511 keV photons, a single detector timing resolution for the LYSO and LaBr3 detectors of 305 ps and 225 ps FWHM, respectively, was achieved. The intrinsic timing resolution of bare LaBr3:Ce(5%) crystals coupled to SiPMs was studied using small (3×3×5 mm3) crystals coupled to single Hamamatsu MPPC S10362-33-050C SiPMs. For 511 keV photon pairs, a coincidence resolving time (CRT) of 101 ps FWHM was obtained. The setup and analysis of the experiments will be presented and favourable conclusions for TOF-PET using sensor arrays on monolithic crystals will be drawn.Speaker: Dr Peter Dendooven (KVI, University of Groningen)
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Optimization of a table-top synchrotron light source for radiological applicationsWithin the Seventh Framework Programme (FP7) of the European Commission, a three-year project named LABSYNC has been recently funded with the aim of designing a complete small facility around the MIRRORCLE light source, a laboratory sized commercial synchrotron developed in Japan [1]. The Medical Physics group of Ferrara University is one of the seven partners of the LABSYNC consortium. Within the project, we will be responsible for the design of an X-ray imaging beamline for diagnostic and therapy applications owing to the broad experience in the physics of diagnostic radiology acquired through the years, in particular for the application of synchrotron radiation to mammography and the development of tunable quasi-monochromatic x-ray beams. Preliminary investigations have confirmed the potential of small-scale synchrotron light sources for medical imaging applications. Indeed, Monte Carlo simulations have demonstrated that x-ray beams generated by the interaction of MeV electrons with target materials of diagnostic interest are far more intense than those generated by conventional x-ray tubes [2]. Furthermore, significant improvement in x-ray beam monochromaticity can be achieved by viewing the x-ray emission from a direction orthogonal or antiparallel to that of the incident electron beam. Since the energy range involved is significantly beyond the diagnostic range an optimization of x-ray detector characteristics is also desirable. Finally, if electron beams with energies of about 20 MeV will be available then also monochromatic X-rays produced by Parametric X-ray Radiation might be tested. [1] http://www.kuleuven.be/labsync/ [2] M. Marziani et al "Optimization of radiography applications using x-ray beams emitted by compact accelerators.", Med. Phys. 36, 2009.Speaker: Prof. Mauro Gambaccini (University of Ferrara)
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Clinical and Pre-clinical applications spectral x-ray detectorsPhoton counting detectors are of growing importance in medical imaging because they enable routine measurement of photon energy. Detectors, such as Medipix2 and Medipix3, record the energy of incident photons with minimal loss of spatial resolution. This is being investigated for both pre-clinical and clinical applications.Early investigations and clinical guidance suggest that computed tomography (CT) is an appropriate modality. For CT, detectors need only cover a thin arc. With Medipix this can be achieved using a 2 X n array. Also, CT can be performed with dead spaces and inhomogeneity across the active area. This is important because high quantum efficiency sensor, such as CdTe or GaAs, are difficult to produce. Medipix detectors achieve the necessary count rates for full body CT by having small pixels each counting at near megahertz rates. Clinical experience with dual energy systems (using kV switching) have shown that CT provides the most clinically relevant data. Applications under investigation by the Medipix3 and partners include: K-edge imaging: Using spectral information to measure heavy elements (eg. preparations of iodine, barium, and gadolinium). Atomic substitution: Replacing potassium or calcium with chemical analogues such as strontium or rubidium. Nano-particles: Particles containing heavy atom are currently being manufacturing to measure the porosity of liver sinusoids. Improved soft tissue contrast: Using dual energy system it has been shown that image contrast for soft tissue can be improved. e.g. iron and calcium within vascular plaques. Results of biological specimens from a Medipix based MARS scanner (Medipix All Resolution System) will be presented.Speaker: Dr Anthony Butler (Univ. Canterbury, Dept. Phys. Astro)
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The MAGIC-5 lung CAD systemsLung cancer accounts for the most common cause of cancer-related deaths in the United States with some 160000 deaths, i.e. around 28% of all cancer deaths, expected in 2009. Low-dose X-ray Computed Tomography (CT) is a reliable tool in terms of lung cancer early diagnosis: the radiation dose for a screening session is smaller than that of clinical CT scans and lung nodules smaller in diameter are more likely to be diagnosed. As a matter of fact, large scale screening programs based on lung CT scans are time consuming: each case report takes from 30 minutes to 1 hour. However, when assisted by Computer Aided Detection (CAD) systems, radiologists have been shown to perform with a better efficiency in terms of both sensitivity and time saving. We present the CAD systems for lung nodule detection in chest CT scans developed in the framework of the Medical Applications on a Grid Infrastructure Connection (MAGIC-5) Project, granted by the italian National Institute of Nuclear Physics (INFN). The project started as a spin-off of high energy physics software development and involves a community of researchers in constant contact with - some of them also involved in - Astroparticle and High Energy Physics experiments. The MAGIC-5 CAD systems consist of several pattern recognition modules, based on statistical and adaptive algorithms: i) lung parenchyma segmentation; ii) detection of nodule candidates; iii) feature extraction; vi) false positive reduction; v) classification of nodule candidates. The systems were tested on CT scans from three different databases: Italung CT Trial database (20 CTs); ANODE09 competition (5 CTs); LIDC database (83 CTs). The most relevant results, as well as the prospects, will be presented and discussed.Speaker: Prof. Roberto Bellotti (Università di Bari and INFN)
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Discussion
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Coffee Break and Poster Walk 500/1-001 - Main Auditorium
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Session 4: Novel technologies in radiation therapy
Chair: Ugo Amaldi (Univ. Milano and TERA Foundation), Rapporteur: Purification Tejedor-Del-Real (European Commission, Brussels)
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A study on repainting strategies for treating moving targets with proton pencil beam scanning for the new Gantry 2 at PSITreating moving targets using a scanning gantry for proton therapy is a challenging, unexplored and unresolved problem. The interference of organ motion with the sequence of the beam delivery produces uncontrolled dose inhomogeneities within the target. One promising approach to overcome this difficulty is to increase the speed of scanning in order to apply the dose repeatedly (so called repainting). To obtain sufficiently high scanning speeds a new, technologically improved gantry - Gantry 2 - has been designed and is currently under construction at PSI. As there are many possible repainting strategies, the way repainting will be implemented on Gantry 2 will depend on the result of a careful analysis of the various treatment delivery strategies available. To this aim, and prior to the start of experimental work with Gantry 2, simulations of dose distribution errors due to organ motion under various beam delivery strategies were investigated. In total over 200'000 dose distributions have been simulated and analyzed and selected results are discussed. From the obtained results we are confident to treat moderately moving targets on Gantry 2 using repainted pencil beam spot scanning. Continuous line scanning seems to be the most elegant solution, it provides higher repainting rates and produces superior results but is probably more difficult to realize. For larger motion amplitudes continuous line scanning still shows good results. To further reduce the dose inhomogeneity within the target volume and safety margins, gating or a breath hold technique is planned to be used for larger motion amplitudes.Speaker: Mr Silvan Zenklusen (Paul Scherrer Institute, ETH Zurich)
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Mitigation of target motion in scanned ion beam therapyScanned ion beam therapy is an innovative technique for conformal treatment of tumors with high sparing of organs at risk in the vicinity of the target. Based on the positive experience of pilot studies in research centers several clinical facilities are currently constructed throughout Europe with the first patients already being treated at the Heidelberg Ion Beam Therapy Center. Currently scanned ion beam therapy is limited to tumors that can be immobilized. In sites that move intra-fractionally such as the lung which is influenced by respiratory motion the interference of target motion and scanning process leads to inhomogeneous dose coverage of the clinical target volume even if margins are used. This interference is typically referred to as interplay. The motion mitigation techniques rescanning, gating, and beam tracking have been proposed to allow treatment of intra-fractionally moving tumors. Rescanning breaks the interplay patterns by multiple irradiations of the planning target volume per fraction with proportionally less dose. Gating limits beam delivery to e.g. the end-exhale part of the breathing cycle resulting in reduced motion amplitudes at longer treatment times. Beam Tracking compensates target motion by adapting all beam parameters and thus does not require motion-related expansion of the clinical target volume. At GSI, rescanning, gating, and beam tracking were implemented as experimental treatment delivery option. In addition, our treatment planning system TRiP was extended to 4D capability allowing dosimetric comparison between the different techniques. Within the contribution experimental results will be presented. In combination with data from treatment planning studies the pros and cons of the different motion will be discussed.Speaker: Dr Christoph Bert (GSI)
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The TOM'5 System for Multibeam TomotherapyIntroduction: The idea of tomotherapy is the most comprehensive IMRT concept for optimization of today tumour therapy with photons. It refers to a radiation treatment with a sequential exposure of body slices. For realization of this concept there are some technical developments to be found. Most of them are based on a multitude of beam angles set in place by a rotating gantry of the treatment device. Materials and methods: The apparatus for multibeam tomotherapy uses a ring-like gantry with a distinct set of five stationary treatment heads (Achterberg and Müller 2007). This proposed system patented by the authors is creating arbitrary dose distributions through intensity-modulation of fan beams by a combination of MLC operation and patient table movement. We have made a simulation to evaluate the performance characteristics of our unit. By the means of the Monte-Carlo-programme BEAM we studied design and treatment geometry. The developed algorithm „Multifocal MLC-Positioning“ for a synchronized driving of multileaf collimation and table movement allows us to perform radiation treatment planning. With BEAM and the treatment planning system Pinnnacle3 (Philips Medical Systems) dose distributions have been produced. Results and discussion: We present an optimized design of our static tomotherapy device and calculated treatment times and dose distributions of different patient cases. The examination of usual results of classic radiation therapy, conventional IMRT, other tomotherapy devices and the treatment with heavy particles (protons, carbon) shows the potential of the new system. Achterberg, N. and Müller, R.G., Med. Phys. 34 (2007) 3926-3942.Speaker: Dr Nils Achterberg (Strahlenklinik-Universitätsklinikum Erlangen)
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Electron cooling application for cancer therapy accelerator facilityBudker Institute of Nuclear Physics (BINP, Novosibirsk) is engaged in R&D of the new cancer therapy accelerator system based on the synchrotron with electron cooling. The electron cooling is used for the ion beam accumulation in process of repeated multi turn injection into the main synchrotron from the fast cycling booster. After acceleration of ions the electron cooling is used for decreasing of beam emittance and momentum spread and for follow extraction of ion beam small fractions according to the irradiation process. Cold ion beam allows decreasing the apertures of synhrotron, high energy transfer lines and gantry. The computer simulations results are in good agreement with experimental data obtained during the CSRe commissioning. Also, the electron cooling can be applied for accumulation of short lived radioactive nuclei which could be useful for cancer therapy. Such technology opens the possibility to realize the irradiation with online PET visualization.Speaker: Mr Vladimir Vostrikov (BINP, Novosibirsk, Russia)
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A cyclotron-linac complex for carbon ion therapyA cyclotron-linac complex for carbon ion therapy A. Degiovanni, U. Amaldi, R. Bonomi, M. Garlasché, A. Garonna, P. Pearce, S. Verdù Andres and R. Wegner TERA Foundation, Via Puccini 11, Novara, Italy The machines used today for carbon therapy are 20-25 m diameter synchrotrons. For the ARCHADE project IBA is building a 400 MeV/u superconducting cyclotron weighting 700 tons and needing a 15 metres long Energy Selection System. In the years 1993-1995 TERA designed a proton linac (LIBO = LInac BOoster) which runs at 3 GHz. A module was built with CERN and INFN and accelerated protons with the expected gradient: 16 MV/m. A 27 MV/m gradient was also obtained, which entails a peak surface field of 2.5 Kilpatrick. TERA is now working on CABOTO (Carbon BOoster for Therapy in Oncology) which is placed downstream of a superconducting cyclotron. After a 3 GHz design, to reduce the overall length the frequency has been increased to 5.7 GHz. This paper describes such a fast-cycling cyclotron-linac complex which runs at 300 Hz for the multipainting of moving tumours. In 23 metres the linac accelerates from 120 MeV/u to 400 MeV/u either C+6 ions or H2+ molecules. The 300 Hz source is the Electron Beam Ion Source EBIS-SC by DReEBIT (Dresden) which produces in 3 μs more that 108 C+6 ions. The K = 480 cyclotron weighs about 170 tons and the Cell Coupled Linac is made of eighteen 1.3 m long units (gradient = 40 MV/m, Kilpatrick = 2.9) powered by solid state modulators equipped with 12 MW klystrons. By switching off the klystrons, the cyclotron-linac complex produces - in eighteen 15-16 MeV steps - beams of either C+6 ions or H2+ molecules with energies in the range 120 - 400 MeV/u. Smaller steps are obtained with a segmented 20 mm absorber and no Energy Selection System.Speaker: Mr Alberto Degiovanni (TERA Foundation)
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A proposal for a low-cost size superconducting multi-use accelerating facility for protons or light ions (LOCMAF)The growing incidence of cancer, its high mortality level and need for progress in the therapy of patients are still among the dominant problems in our days. As available statistics show, about 70% of cancer patients are treated by radiotherapy. According to estimates of the leading radiotherapy experts, hadron therapy (HT) will significantly complement the radiotherapy using traditional (x-ray, gamma, electron beam) sources, so that the creation of clinical HT centers represents the strategy of development in this field. It is proposed the creation of a scientific consortium of the CERN-MS and NON-MS, in order to study a project for final design, construction and commissioning of, a ready for operation, a low-cost size superconducting multi-use accelerating facility for protons or light ions (LOCMAF) for use of: i) Hadron Therapy (HD), ii) Radio-isotopes Production (RiP) and iii) Tests Beam (TB) studies for the material science and medical physics research plus other applications. The building, under the frame of the CERN Directorate for Accelerators and Technology, of a low-cost small size superconducting multi-use accelerating facility for protons or light ions and the training of the scientific personnel to its operation, materializes pragmatically the prospected Knowledge and Technology Transfer (KTT) from CERN to the involved countries, MS and non-MS, in an unique, solid and realistic way, coming exclusively from the research experience and results for a about 55 years of CERN operation.Speaker: Evangelos Gazis (CERN-NTUA)
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General Discussion
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Workshop Dinner Globe 1st Floor
Globe 1st Floor
CERN
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Summary Talk Session 1: B.Jones (Oxford) 500/1-001 - Main AuditoriumSpeaker: B. Jones (Oxford)
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Summary Talk Session 2: U. Koester (Grenoble) 500/1-001 - Main AuditoriumSpeaker: U. Koester (ILL)
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Summary Talk Session 3: W. Enghardt (Dresden) 500/1-001 - Main AuditoriumSpeaker: W. Enghardt (TU Dresden)
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Winning Poster talk 500/1-001 - Main Auditorium
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Final general discussion 500/1-001 - Main Auditorium
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Keynote closing speakers: D. Townsend (Singapore Bioimaging Consortium), J.Bourhis (Institute Gustave Roussy, ESTRO) 500/1-001 - Main Auditorium
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Closing remarks: R. Heuer, CERN Director General 500/1-001 - Main Auditorium
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