Browsing by Author "Safavi-Naeini, M"

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    Application of an SOI microdosimeter for monitoring of neutrons in various mixed radiation field environments
    (Institute of Electrical and Electronics Engineers (IEEE), 2022-03-01) Pan, VA; Vohradsky, J; James, B; Pagani, F; Chartier, L; Debrot, E; Pastuovic, Z; Cutajar, D; Poder, J; Nancarrow, M; Pereloma, E; Bolst, D; Lee, SH; Inaniwa, T; Safavi-Naeini, M; Prokopovich, DA; Guatelli, S; Petasecca, M; Lerch, MLF; Povoli, M; Kok, A; Tran, LT; Rosenfeld, AB
    Radiation monitoring in space radiation is complex due to galactic cosmic rays (GCRs), solar particle events (SPEs), and albedo particles. Thermal neutrons are an important component in the Moon radiation albedo field which can cause single event upset (SEU) in electronics when they interact with the 10 B present in electronic components. In this work, we studied an application of silicon on insulator (SOI) microdosimeters for neutron monitoring in various mixed radiation field environments. A 10- μm SOI microdosimeter was utilized in conjunction with a 10 B 4 C thin-film converter to successfully measure the thermal neutron contribution out of field of a therapeutic proton beam as well as an 18-MV X-ray linear accelerator (LINAC). The microdosimeter was placed downstream of the Bragg peak (BP) as well as laterally out of field of the proton beam and at two positions along the treatment couch of the 18-MV LINAC. It was demonstrated that the 10- μm SOI microdosimeter with 10 B 4 C converter is suitable for detection of thermal neutrons with excellent discrimination of gamma, fast and thermal neutron components in the presence of a gamma-neutron pulsed field of an 18-MV LINAC. To reduce the gamma contribution and further improve detection of neutrons in mixed radiation fields, a new 2 μm Mushroom-planar microdosimeter was fabricated and characterized in detail using an ion beam induced charge collection (IBIC) technique with 1.78 MeV He2+ ions. It was demonstrated that this 2 μm SOI microdosimeter can be operated in a passive mode. The SOI microdosimeter with the 10 B 4 C converter can be recommended for the detection of thermal neutrons for SEU prediction in the mixed gamma-neutron fields during space missions, especially for the Moon mission.© Copyright 2025 IEEE
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    BENEdiCTE (Boron Enhanced NEutron CapTurE) gamma-ray detection module
    (IEEE, 2021-10-16) Caracciolo, A; Di Vita, D; Buonanno, L; D'Adda, I; Carminati, M; Charcon, A; Kielly, M; Safavi-Naeini, M; Fiorini, C
    We present a gamma-ray detection module for Neutron Capture Enhanced Particle Therapy (NCEPT). The system has been optimised for boron-10 neutron capture agents that can be used for dose enhancement in proton and heavy ion therapy. The goal of the module is to distinguish the photopeak at 478 keV from the prompt-gamma emission resulting from the ion-target nuclear interactions. The module consists of a compact 64-channel module, with a large array of SiPM coupled to a 2" diameter and 2" thickness cylindrical LaBr 3 :Ce scintillator crystal (63 ph/keV conversion efficiency, 16 ns decay time). The electronic front-end ASIC features low-noise processing of photodetector signals, while the pixellated SiPMs detector and individual readout allows for position sensitivity in the crystal. We have characterised the energy resolution of the system experimentally, demonstrating an excellent energy resolution (3.27% at 662 keV), together with the capability of the FPGA-based DAQ integrated in the module to deploy an external synchronization signal to the ion beam bunches, in order to generate anti-coincidence windows. This feature provides a mechanism to distinguish and reject scintillation events from prompt gammas, enhancing the signal-to-background ratio of the spectrometer. © 2021 IEEE
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    BeNEdiCTE (Boron Neutron Capture): a versatile gamma-ray detection module for boron neutron capture therapy
    (Institute of Electrical and Electronics Engineers (IEEE), 2022-02-25) Caracciolo, A; Buonanno, L; Vita, DD; D’Adda, I; Chacon, A; Kielly, M; Carminati, M; Safavi-Naeini, M; Fiorini, C
    We present a gamma-ray detection module for quantifying the boron neutron capture events that occur in the boron neutron capture therapy (BNCT) and neutron capture enhanced particle therapy (NCEPT). The goal of the module is to differentiate between the background prompt gamma peaks and the 478-keV neutron capture photopeak, in order to estimate the dose delivered to the patient. It is a compact module, coupling a large array of 64 silicon photomultipliers (SiPMs) with a 2' × 2' cylindrical LaBr3(Ce+Sr) scintillator crystal (73-ph/keV light yield, 25-ns decay time). The electronic front-end ASIC features low-noise processing of photodetector signals, while SiPMs pixellation and individual readout allow for position sensitivity in the crystal, although position estimation is not the object of this work. The module experimental characterization shows excellent energy resolution (2.7% FWHM at 662keV), that allows to discriminate the neutron capture photons at 478keV from the annihilation photons at 511keV. The module features also an anti-coincidence circuit that provides a mechanism to distinguish and reject scintillation events created within specific temporal windows, thus enhancing the signal-to-background ratio of the spectrometer. © Copyright 2024 IEEE
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    Comparative study of alternative Geant4 hadronic ion inelastic physics models for prediction of positron-emitting radionuclide production in carbon and oxygen ion therapy
    (IOP Publishing, 2019-08-01) Chacon, A; Guatelli, S; Rutherford, H; Bolst, D; Mohammadi, A; Ahmed, A; Nitta, M; Nishikido, F; Iwao, Y; Tashima, H; Yoshida, E; Akamatsu, G; Takyu, S; Kitagawa, A; Hofmann, T; Pinto, M; Franklin, DR; Parodi, K; Yamaya, T; Rosenfeld, AB; Safavi-Naeini, M
    The distribution of fragmentation products predicted by Monte Carlo simulations of heavy ion therapy depend on the hadronic physics model chosen in the simulation. This work aims to evaluate three alternative hadronic inelastic fragmentation physics options available in the Geant4 Monte Carlo radiation physics simulation framework to determine which model most accurately predicts the production of positron-emitting fragmentation products observable using in-beam PET imaging. Fragment distributions obtained with the BIC, QMD, and INCL + + physics models in Geant4 version 10.2.p03 are compared to experimental data obtained at the HIMAC heavy-ion treatment facility at NIRS in Chiba, Japan. For both simulations and experiments, monoenergetic beams are applied to three different block phantoms composed of gelatin, poly(methyl methacrylate) and polyethylene. The yields of the positron-emitting nuclei 11C, 10C and 15O obtained from simulations conducted with each model are compared to the experimental yields estimated by fitting a multi-exponential radioactive decay model to dynamic PET images using the normalised mean square error metric in the entrance, build up/Bragg peak and tail regions. Significant differences in positron-emitting fragment yield are observed among the three physics models with the best overall fit to experimental 12C and 16O beam measurements obtained with the BIC physics model. © 2019 Commonwealth of Australia, Australian Nuclear Science and Technology Organisation, ANSTO.
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    Detection and discrimination of neutron capture events for NCEPT dose quantification
    (Springer Nature Limited, 2022-04-07) Chacon, A; Kielly, M; Rutherford, H; Franklin, DR; Caracciolo, A; Buonanno, L; D'Adda, I; Rosenfeld, AB; Guatelli, S; Carminati, M; Fiorini, C; Safavi-Naeini, M
    Neutron Capture Enhanced Particle Therapy (NCEPT) boosts the effectiveness of particle therapy by capturing thermal neutrons produced by beam-target nuclear interactions in and around the treatment site, using tumour-specific 10B or 157Gd-based neutron capture agents. Neutron captures release high-LET secondary particles together with gamma photons with energies of 478 keV or one of several energies up to 7.94 MeV, for 10B and 157Gd, respectively. A key requirement for NCEPT’s translation is the development of in vivo dosimetry techniques which can measure both the direct ion dose and the dose due to neutron capture. In this work, we report signatures which can be used to discriminate between photons resulting from neutron capture and those originating from other processes. A Geant4 Monte Carlo simulation study into timing and energy thresholds for discrimination of prompt gamma photons resulting from thermal neutron capture during NCEPT was conducted. Three simulated 300×300×300 mm3 cubic PMMA targets were irradiated by 4He or 12C ion beams with a spread out Bragg peak (SOBP) depth range of 60 mm; one target is homogeneous while the others include 10×10×10 mm3 neutron capture inserts (NCIs) of pure 10B or 157Gd located at the distal edge of the SOBP. The arrival times of photons and neutrons entering a simulated 50×50×50 mm3 ideal detector were recorded. A temporal mask of 50–60 ns was found to be optimal for maximising the discrimination of the photons resulting from the neutron capture by boron and gadolinium. A range of candidate detector and thermal neutron shielding materials were simulated, and detections meeting the proposed acceptance criteria (i.e. falling within the target energy window and arriving 60 ns post beam-off) were classified as true or false positives, depending on their origin. The ratio of true/false positives (RTF) was calculated; for targets with 10B and 157Gd NCIs, the detector materials which resulted in the highest RTF were cadmium-shielded CdTe and boron-shielded LSO, respectively. The optimal irradiation period for both carbon and helium ions was 1 µs for the 10B NCI and 1 ms for the 157Gd NCI. © The Authors, Creative Commons Attribution 4.0 International Licence.
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    Dose quantification in carbon ion therapy using in-beam positron emission tomography
    (IOP Publishing, 2020-12-07) Rutherford, H; Chacon, A; Mohammadi, A; Takyu, S; Tashima, H; Yoshida, E; Nishikido, F; Hofmann, T; Pinto, M; Franklin, DR; Yamaya, T; Parodi, K; Rosenfeld, AB; Guatelli, S; Safavi-Naeini, M
    This work presents an iterative method for the estimation of the absolute dose distribution in patients undergoing carbon ion therapy, via analysis of the distribution of positron annihilations resulting from the decay of positron-emitting fragments created in the target volume. The proposed method relies on the decomposition of the total positron-annihilation distributions into profiles of the three principal positron-emitting fragment species - 11C, 10C and 15O. A library of basis functions is constructed by simulating a range of monoenergetic 12C ion irradiations of a homogeneous polymethyl methacrylate phantom and measuring the resulting one-dimensional positron-emitting fragment profiles and dose distributions. To estimate the dose delivered during an arbitrary polyenergetic irradiation, a linear combination of factors from the fragment profile library is iteratively fitted to the decomposed positron annihilation profile acquired during the irradiation, and the resulting weights combined with the corresponding monoenergetic dose profiles to estimate the total dose distribution. A total variation regularisation term is incorporated into the fitting process to suppress high-frequency noise. The method was evaluated with 14 different polyenergetic 12C dose profiles in a polymethyl methacrylate target: one which produces a flat biological dose, 10 with randomised energy weighting factors, and three with distinct dose maxima or minima within the spread-out Bragg peak region. The proposed method is able to calculate the dose profile with mean relative errors of 0.8%, 1.0% and 1.6% from the 11C, 10C, 15O fragment profiles, respectively, and estimate the position of the distal edge of the SOBP to within an average of 0.7 mm, 1.9 mm and 1.2 mm of its true location. © 2020 Commonwealth of Australia, ANSTO
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    Dose reconstruction from PET images in carbon ion therapy: a deconvolution approach
    (IOP Publishing, 2019-01-01) Hofmann, T; Pinto, M; Mohammadi, A; Nitta, M; Nishikido, F; Iwao, Y; Tashima, H; Yoshida, E; Chacon, A; Safavi-Naeini, M; Rosenfeld, AB; Yamaya, T; Parodi, K
    Dose and range verification have become important tools to bring carbon ion therapy to a higher level of confidence in clinical applications. Positron emission tomography is among the most commonly used approaches for this purpose and relies on the creation of positron emitting nuclei in nuclear interactions of the primary ions with tissue. Predictions of these positron emitter distributions are usually obtained from time-consuming Monte Carlo simulations or measurements from previous treatment fractions, and their comparison to the current, measured image allows for treatment verification. Still, a direct comparison of planned and delivered dose would be highly desirable, since the dose is the quantity of interest in radiation therapy and its confirmation improves quality assurance in carbon ion therapy. In this work, we present a deconvolution approach to predict dose distributions from PET images in carbon ion therapy. Under the assumption that the one-dimensional PET distribution is described by a convolution of the depth dose distribution and a filter kernel, an evolutionary algorithm is introduced to perform the reverse step and predict the depth dose distribution from a measured PET distribution. Filter kernels are obtained from either a library or are created for any given situation on-the-fly, using predictions of the β + -decay and depth dose distributions, and the very same evolutionary algorithm. The applicability of this approach is demonstrated for monoenergetic and polyenergetic carbon ion irradiation of homogeneous and heterogeneous solid phantoms as well as a patient computed tomography image, using Monte Carlo simulated distributions and measured in-beam PET data. Carbon ion ranges are predicted within less than 0.5 mm and 1 mm deviation for simulated and measured distributions, respectively. © 2019 Institute of Physics and Engineering in Medicine.
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    Dose reconstruction from PET images in carbon ion therapy: a deconvolution approach using an evolutionary algorithm
    (Institute of Electrical and Electronics Engineers, 2017-10-28) Hofmann, T; Fochi, A; Pinto, M; Mohammadi, A; Nitta, M; Nishikido, F; Iwao, Y; Tashima, H; Yoshida, E; Safavi-Naeini, M; Chacon, A; Rosenfeld, AB; Yamaya, T; Parodi, K
    Dose monitoring and range verification are important tools in carbon ion therapy. For their implementation, positron emission tomography (PET) can be used to image the β+-activation of tissue during treatment. Predictions of these β+-activity distributions are usually obtained from Monte Carlo simulations, which demands high computational time and thus limits the applicability of this technique in clinical scenario. Nevertheless, it is desirable to explore faster approaches able to give such a prediction, since only its comparison with the measured distributions allows a definite assessment of potential range deviations from the planned treatment. For the first time, we present an approach to perform deconvolution from PET data in carbon ion therapy and reconstruct the dose. A filtering method is used to predict positron emitter profiles from dose profiles in short time. In order to reverse the convolution and estimate a dose distribution from a positron emitter distribution, we apply an evolutionary algorithm. Filters are obtained from either a library or are created in advance for a specific problem, assuming that a prediction of the positron emitter distribution is available. To perform the latter method and find the best filter for a specific problem, we use another evolutionary algorithm, hence optimizing the filter on-the-fly for the given treatment scheme. The application of our method is shown for dose and positron emitter distributions in homogeneous phantoms using simulated and newly measured online PET data. Carbon ion ranges can be predicted within 2 mm and the shape of the dose distribution is reconstructed with an overall promising agreement.
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    Erratum: Influence of momentum acceptance on range monitoring of 11C and 15O ion beams using in-beam PET (2020 Phys. Med. Biol. 65 125006)
    (IOP Publishing, 2020-11-21) Mohammadi, A; Tashima, H; Iwao, Y; Takyu, S; Akamatsu, G; Kang, HG; Nishikido, F; Yoshida, E; Chacon, A; Safavi-Naeini, M; Parodi, K; Yamaya, T
    In heavy-ion therapy, the stopping position of primary ions in tumours needs to be monitored for effective treatment and to prevent overdose exposure to normal tissues. Positron-emitting ion beams, such as 11C and 15O, have been suggested for range verification in heavy-ion therapy using in-beam positron emission tomography (PET) imaging, which offers the capability of visualizing the ion stopping position with a high signal-to-noise ratio. We have previously demonstrated the feasibility of in-beam PET imaging for the range verification of 11C and 15O ion beams and observed a slight shift between the beam stopping position and the dose peak position in simulations, depending on the initial beam energy spread. In this study, we focused on the experimental confirmation of the shift between the Bragg peak position and the position of the maximum detected positron-emitting fragments via a PET system for positron-emitting ion beams of 11C (210 MeV u−1) and 15O (312 MeV u−1) with momentum acceptances of 5% and 0.5%. For this purpose, we measured the depth doses and performed in-beam PET imaging using a polymethyl methacrylate (PMMA) phantom for both beams with different momentum acceptances. The shifts between the Bragg peak position and the PET peak position in an irradiated PMMA phantom for the 15O ion beams were 1.8 mm and 0.3 mm for momentum acceptances of 5% and 0.5%, respectively. The shifts between the positions of two peaks for the 11C ion beam were 2.1 mm and 0.1 mm for momentum acceptances of 5% and 0.5%, respectively. We observed larger shifts between the Bragg peak and the PET peak positions for a momentum acceptance of 5% for both beams, which is consistent with the simulation results reported in our previous study. The biological doses were also estimated from the calculated relative biological effectiveness (RBE) values using a modified microdosimetric kinetic model (mMKM) and Monte Carlo simulation. Beams with a momentum acceptance of 5% should be used with caution for therapeutic applications to avoid extra dose to normal tissues beyond the tumour when the dose distal fall-off is located beyond the treatment volume. © 2020 Institute of Physics and Engineering in Medicine.
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    Evaluation of silicon detectors with integrated JFET for biomedical applications
    (Institute of Electrical and Electronics Engineers (IEEE), 2009-06) Safavi-Naeini, M; Franklin, DR; Lerch, MLF; Petasecca, M; Pignatel, G; Reinhard, MI; Dalla Betta, GF; Zorzi, N; Rosenfeld, AB
    This paper presents initial results from electrical, spectroscopic and ion beam induced charge (IBIC) characterisation of a novel silicon PIN detector, featuring an on-chip n -channel JFET and matched feedback capacitor integrated on its p-side (frontside). This structure reduces electronic noise by minimising stray capacitance and enables highly efficient optical coupling between the detector back-side and scintillator, providing a fill factor of close to 100%. The detector is specifically designed for use in high resolution gamma cameras, where a pixellated scintillator crystal is directly coupled to an array of silicon photodetectors. The on-chip JFET is matched with the photodiode capacitance and forms the input stage of an external charge sensitive preamplifier (CSA). The integrated monolithic feedback capacitor eliminates the need for an external feedback capacitor in the external electronic readout circuit, improving the system performance by eliminating uncontrolled parasitic capacitances. An optimised noise figure of 152 electrons RMS was obtained with a shaping time of 2 mus and a total detector capacitance of 2 pF. The energy resolution obtained at room temperature (2°C) at 27 keV (direct interaction of I-125 gamma rays) was 5.09%, measured at full width at half maximum (FWHM). The effectiveness of the guard ring in minimising the detector leakage current and its influence on the total charge collection volume is clearly demonstrated by the IBIC images. © 2009, Institute of Electrical and Electronics Engineers (IEEE)
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    Experimental investigation of the characteristics of radioactive beams for heavy ion therapy
    (Wiley, 2020-07) Chacon, A; James, B; Tran, LT; Guatelli, S; Chartier, L; Prokopovich, DA; Franklin, DR; Mohammadi, A; Nishikido, F; Iwao, Y; Akamatsu, G; Takyu, S; Tashima, H; Yamaya, T; Parodi, K; Rosenfeld, AB; Safavi-Naeini, M
    Purpose This work has two related objectives. The first is to estimate the relative biological effectiveness of two radioactive heavy ion beams based on experimental measurements, and compare these to the relative biological effectiveness of corresponding stable isotopes to determine whether they are therapeutically equivalent. The second aim is to quantitatively compare the quality of images acquired postirradiation using an in‐beam whole‐body positron emission tomography scanner for range verification quality assurance. Methods The energy deposited by monoenergetic beams of C at 350 MeV/u, O at 250 MeV/u, C at 350 MeV/u, and O at 430 MeV/u was measured using a cruciform transmission ionization chamber in a water phantom at the Heavy Ion Medical Accelerator in Chiba (HIMAC), Japan. Dose‐mean lineal energy was measured at various depths along the path of each beam in a water phantom using a silicon‐on‐insulator mushroom microdosimeter. Using the modified microdosimetric kinetic model, the relative biological effectiveness at 10% survival fraction of the radioactive ion beams was evaluated and compared to that of the corresponding stable ions along the path of the beam. Finally, the postirradiation distributions of positron annihilations resulting from the decay of positron‐emitting nuclei were measured for each beam in a gelatin phantom using the in‐beam whole‐body positron emission tomography scanner at HIMAC. The depth of maximum positron‐annihilation density was compared with the depth of maximum dose deposition and the signal‐to‐background ratios were calculated and compared for images acquired over 5 and 20 min postirradiation of the phantom. Results In the entrance region, the was 1.2 ± 0.1 for both C and C beams, while for O and O it was 1.4 ± 0.1 and 1.3 ± 0.1, respectively. At the Bragg peak, the was 2.7 ± 0.4 for C and 2.9 ± 0.4 for C, while for O and O it was 2.7 ± 0.4 and 2.8 ± 0.4, respectively. In the tail region, could only be evaluated for carbon; the was 1.6 ± 0.2 and 1.5 ± 0.1 for C and C, respectively. Positron emission tomography images obtained from gelatin targets irradiated by radioactive ion beams exhibit markedly improved signal‐to‐background ratios compared to those obtained from targets irradiated by nonradioactive ion beams, with 5‐fold and 11‐fold increases in the ratios calculated for the O and C images compared with the values obtained for O and C, respectively. The difference between the depth of maximum dose and the depth of maximum positron annihilation density is 2.4 ± 0.8 mm for C, compared to −5.6 ± 0.8 mm for C and 0.9 ± 0.8 mm for O vs −6.6 ± 0.8 mm for O. Conclusions The values for C and O were found to be within the 95% confidence interval of the RBEs estimated for their corresponding stable isotopes across each of the regions in which it was evaluated. Furthermore, for a given dose, C and O beams produce much better quality images for range verification compared with C and O, in particular with regard to estimating the location of the Bragg peak. © 2024 American Association of Physicists in Medicine.
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    Fluorine-18 radiolabelling and in vitro / in vivo metabolism of [18F]D4-PBR111
    (John Wiley & Sons, Inc, 2019-05-26) Wyatt, NA; Safavi-Naeini, M; Wotherspoon, ATL; Arthur, A; Nguyen, AP; Parmar, A; Hamze, H; Day, CM; Zahra, D; Matesic, L; Davis, E; Rahardjo, GL; Yepuri, NR; Shepherd, R; Murphy, RB; Pham, TQ; Nguyen, VH; Callaghan, PD; Holden, PJ; Grégoire, MC; Darwish, TA; Fraser, BH
    Objectives The purinergic receptor P2X ligand-gated ion channel type 7 (P2X7R) is an adenosine triphosphate (ATP)-gated ion-channel, and P2X7R is a key player in inflammation. P2X7R is an emerging therapeutic target in central nervous system (CNS) diseases including Alzheimer's disease (AD) and Parkinson's disease (PD), because P2X7R also plays a pivotal role in neuroinflammation. P2X7R represents a potential molecular imaging target for neuroinflammation via biomedical imaging technique positron emission tomography (PET), and several radioligands targeting P2X7R have been developed and evaluated in animals. In our previous work, we have developed and characterized [11C]GSK1482160 as a P2X7R radioligand for neuroinflammation,2 clinical evaluation of [11C]GSK1482160 in healthy controls and patients is currently underway, and the estimation of radiation dosimetry for [11C]GSK1482160 in normal human subjects has been reported.3 Since the half-life (t1/2) of radionuclide carbon-11 is only 20.4 min, it is attractive for us to develop derivatives of [11C]GSK1482160, which can be labeled with the radionuclide fluorine-18 (t1/2, 109.7 min), and a fluorine-18 ligand would be ideal for widespread use.4 To this end, a series of [18F]fluoroalkyl including [18F]fluoromethyl (FM), [18F]fluoroethyl (FE), and [18F]fluoropropyl (FP) derivatives of GSK1482160 have been prepared and examined as new potential P2X7R radioligands. © 2019 The Authors
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    Gd-TPP-DOTA reduces cell viability in cancer cells via synchrotron radiotherapy
    (Australian National University, 2021-08-24) Middleton, RJ; Howell, NR; Livio, E; Wyatt, NA; Chacon, A; Fraser, BH; Barnes, M; Cameron, M; Rendina, LM; Häusermann, D; Lerch, MLF; Safavi-Naeini, M
    High-Z elements have been proposed as radiosensitisers in X-ray photon radiotherapy due to their emission of multiple high-LET photo- and Auger electrons following X-ray irradiation. Gadolinium is a particularly attractive candidate radiosensitiser, since it can also be used as an MRI contrast agent. In this study, we report on the efficacy of Gd-triphenylphosphonium salt-DOTA (Gd(III)-TPP-DOTA) for synchrotron microbeam radiation therapy dose enhancement. The compound utilises the mitochondrial targeting moiety triphenylphosphonium (TPP) to accumulate Gd in the inner mitochondrial membrane. Experiments were conducted using the dynamic mode option at hutch 2B of the Imaging and Medical Beamline at the Australian Synchrotron. Human glioblastoma multiforme cells (T98G cell line) were cultured to 80-90% confluence in T12.5 flasks. Approximately 24 hours prior to irradiation, the cultures were either treated with a 500 μM solution of Gd(III)DOTA-TPP or a vehicle control. Spatial dose distribution of synchrotron broad beam (BB) and single/multiple microbeams were measured using a micron-scale X-Tream dosimetry system and Gafchromic films in air and at 2 cm depth in solid water (same depth as the monolayer of cells in T12.5 flasks). A total of 96 flasks were irradiated, with doses of 0, 1, 2, 3, 4, 5, 10 and 16 Gy delivered in valley (MRT) or uniformly (BB). Post irradiation, each flask was re-seeded into 7 x 96 well-plates to perform the resazurin cell proliferation assay up to 7 days after irradiation. Our preliminary analysis indicates that for cells irradiated by 3 Gy of BB or MRT radiation, the addition of Gd(III)DOTA-TPP results in a reduction in viable cell mass by 24.25% and 25.79%, respectively, compared with untreated flasks. © The Authors
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    An inception network for positron emission tomography based dose estimation in carbon ion therapy
    (IOP Publishing, 2022-09-23) Rutherford, H; Turai, RS; Chacon, A; Franklin, DR; Mohammadi, A; Tashima, H; Yamaya, T; Parodi, K; Rosenfeld, AB; Guatelli, S; Safavi-Naeini, M
    Objective. We aim to evaluate a method for estimating 1D physical dose deposition profiles in carbon ion therapy via analysis of dynamic PET images using a deep residual learning convolutional neural network (CNN). The method is validated using Monte Carlo simulations of 12C ion spread-out Bragg peak (SOBP) profiles, and demonstrated with an experimental PET image. Approach. A set of dose deposition and positron annihilation profiles for monoenergetic 12C ion pencil beams in PMMA are first generated using Monte Carlo simulations. From these, a set of random polyenergetic dose and positron annihilation profiles are synthesised and used to train the CNN. Performance is evaluated by generating a second set of simulated 12C ion SOBP profiles (one 116 mm SOBP profile and ten 60 mm SOBP profiles), and using the trained neural network to estimate the dose profile deposited by each beam and the position of the distal edge of the SOBP. Next, the same methods are used to evaluate the network using an experimental PET image, obtained after irradiating a PMMA phantom with a 12C ion beam at QST’s Heavy Ion Medical Accelerator in Chiba facility in Chiba, Japan. The performance of the CNN is compared to that of a recently published iterative technique using the same simulated and experimental 12C SOBP profiles. Main results. The CNN estimated the simulated dose profiles with a mean relative error (MRE) of 0.7% ± 1.0% and the distal edge position with an accuracy of 0.1 mm ± 0.2 mm, and estimate the dose delivered by the experimental 12C ion beam with a MRE of 3.7%, and the distal edge with an accuracy of 1.7 mm. Significance. The CNN was able to produce estimates of the dose distribution with comparable or improved accuracy and computational efficiency compared to the iterative method and other similar PET-based direct dose quantification techniques. © 2022 Institute of Physics and Engineering in Medicine.
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    Influence of momentum acceptance on range monitoring of 11C and 15O ion beams using in-beam PET
    (IOP Publishing, 2020-06-12) Mohammadi, A; Tashima, H; Iwao, Y; Takyu, S; Akamatsu, G; Kang, HG; Nishikido, F; Yoshida, E; Chacon, A; Safavi-Naeini, M; Parodi, K; Yamaya, T
    In heavy-ion therapy, the stopping position of primary ions in tumours needs to be monitored for effective treatment and to prevent overdose exposure to normal tissues. Positron-emitting ion beams, such as 11C and 15O, have been suggested for range verification in heavy-ion therapy using in-beam positron emission tomography (PET) imaging, which offers the capability of visualizing the ion stopping position with a high signal-To-noise ratio. We have previously demonstrated the feasibility of in-beam PET imaging for the range verification of 11C and 15O ion beams and observed a slight shift between the beam stopping position and the dose peak position in simulations, depending on the initial beam energy spread. In this study, we focused on the experimental confirmation of the shift between the Bragg peak position and the position of the maximum detected positron-emitting fragments via a PET system for positron-emitting ion beams of 11C (210 MeV u-1) and 15O (312 MeV u-1) with momentum acceptances of 5% and 0.5%. For this purpose, we measured the depth doses and performed in-beam PET imaging using a polymethyl methacrylate (PMMA) phantom for both beams with different momentum acceptances. The shifts between the Bragg peak position and the PET peak position in an irradiated PMMA phantom for the 15O ion beams were 1.8 mm and 0.3 mm for momentum acceptances of 5% and 0.5%, respectively. The shifts between the positions of two peaks for the 11C ion beam were 2.1 mm and 0.1 mm for momentum acceptances of 5% and 0.5%, respectively. We observed larger shifts between the Bragg peak and the PET peak positions for a momentum acceptance of 5% for both beams, which is consistent with the simulation results reported in our previous study. The biological doses were also estimated from the calculated relative biological effectiveness (RBE) values using a modified microdosimetric kinetic model (mMKM) and Monte Carlo simulation. Beams with a momentum acceptance of 5% should be used with caution for therapeutic applications to avoid extra dose to normal tissues beyond the tumour when the dose distal fall-off is located beyond the treatment volume. © 2020 Institute of Physics and Engineering in Medicine
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    Localisation of the lines of response in a continuous cylindrical shell PET scanner
    (Institute of Electrical and Electronics Engineers (IEEE), 2019-10-07) Wilson, KJ; Alabd, R; Abolhasan, M; Franklin, DR; Safavi-Naeini, M
    This work presents a technique for localising the endpoints of the lines of response in a PET scanner based on a continuous cylindrical shell scintillator. The technique is demonstrated by applying it to a simulation of a sensitivity-optimised continuous cylindrical shell PET system using two novel scintillator materials -a transparent ceramic garnet, GLuGAG:Ce, and a LuF3:Ce-polystyrene nanocomposite. Error distributions for the endpoints of the lines of response in the axial, tangential and radial dimension as well as overall endpoint spatial error are calculated for three source positions; the resultant distribution of error in the placement of the lines of response is also estimated. © 019 Crown
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    Microdosing, isotopic labeling, radiotracers and metabolomics: relevance in drug discovery, development and safety
    (Taylor & Francis, 2017-12) Wotherspoon, ATL; Safavi-Naeini, M; Banati, RB
    This review discusses the use of stable (13C, 2D) or radioactive isotopes (14C,11C, 18F, 131I, 64Cu, 68Ga) incorporated into the molecular structure of new drug entities for the purpose of pharmacokinetic or -dynamic studies. Metabolite in safety testing requires the administration of pharmacologically active doses. In such studies, radiotracers find application mainly in preclinical animal investigations, whereby LC-MS/MS is used to identify metabolite structure and drug-related effects. In contrast, first-in-human metabolite studies have to be carried out at nonpharmacological doses not exceeding 100 μg (microdose), which is generally too low for metabolite detection by LC-MS/MS. This short-coming can be overcome by specific radio- or isotopic labeling of the drug of interest and measurements using accelerator mass spectroscopy, single-photon emission computed tomography and positron emission tomography. Such combined radioisotope-based approaches permit Phase 0, first-in-human metabolite study. © 2024Informa UK Limited. This work is licensed under a Crown Copyright protection and licensed for use under the Open Government License unless otherwise indicated. Where any of the Crown copyright information in this work is republished or copied to others, the source of the material must be identified and the copyright status under the Open Government License acknowledged.
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    A Monte Carlo model of the Dingo thermal neutron imaging beamline
    (Springer Nature, 2023-12-01) Jakubowski, K; Charcon, A; Tran, LT; Stopic, A; Garbe, U; Bevitt, JJ; Olsen, SR; Franklin, DR; Rosenfeld, AB; Guatelli, S; Safavi-Naeini, M
    In this study, we present a validated Geant4 Monte Carlo simulation model of the Dingo thermal neutron imaging beamline at the Australian Centre for Neutron Scattering. The model, constructed using CAD drawings of the entire beam transport path and shielding structures, is designed to precisely predict the in-beam neutron field at the position at the sample irradiation stage. The model’s performance was assessed by comparing simulation results to various experimental measurements, including planar thermal neutron distribution obtained in-beam using gold foil activation and BC-coated microdosimeters and the out-of-beam neutron spectra measured with Bonner spheres. The simulation results demonstrated that the predicted neutron fluence at the field’s centre is within 8.1% and 2.1% of the gold foil and BC-coated microdosimeter measurements, respectively. The logarithms of the ratios of average simulated to experimental fluences in the thermal (E 0.414 eV), epithermal (0.414 eV < E 11.7 keV) and fast (E 11.7 keV) spectral regions were approximately − 0.03 to + 0.1, − 0.2 to + 0.15, and − 0.4 to + 0.2, respectively. Furthermore, the predicted thermal, epithermal and fast neutron components in-beam at the sample stage position constituted approximately 18%, 64% and 18% of the total neutron fluence. © The Authors - Open Access Open Access This article is licensed under a Creative Commons Attribution 4.0 International.
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    Neutron capture enhanced particle therapy: a frontier in hadron therapy
    (Australian Nuclear Science and Technology Organisation, 2019-09-27) Safavi-Naeini, M
    Neutron Capture Enhanced Particle Therapy (NCEPT) is a radical new paradigm in radiotherapy being developed by an international team led by ANSTO. NCEPT combines the precision of particle therapy with the cancer-specific targeting capability of neutron capture therapy (NCT). NCEPT magnifies the impact of particle therapy by capturing neutrons - produced internally at the target as a by-product of treatment - inside cancer cells, where they deliver extra dose to the tumour (Fig. 1). NCEPT uses low-toxicity agents containing boron-10 and gadolinium-157 which concentrate in cancer cells, already approved or under development for other medical applications. Simulations and experiments on cancer cells have yielded extremely compelling results, indicating that NCEPT achieves equivalent cancer cell control with between ⅓ and ⅕ of the radiation dose compared to particle therapy alone. NCEPT has generated considerable excitement within the radiation oncology communities in Australia, USA, and in particular in Japan, where it has been dubbed “the future of ion-beam radiotherapy”. Initial discussions regarding the first clinical trials in Japan are currently in progress.
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    Opportunistic dose amplification for proton and carbon ion therapy via capture of internally generated thermal neutrons
    (Springer Nature, 2018-11-02) Safavi-Naeini, M; Chacon, A; Guatelli, S; Franklin, DR; Bambery, KR; Grégoire, MC; Rosenfeld, AB
    This paper presents Neutron Capture Enhanced Particle Therapy (NCEPT), a method for enhancing the radiation dose delivered to a tumour relative to surrounding healthy tissues during proton and carbon ion therapy by capturing thermal neutrons produced inside the treatment volume during irradiation. NCEPT utilises extant and in-development boron-10 and gadolinium-157-based drugs from the related field of neutron capture therapy. Using Monte Carlo simulations, we demonstrate that a typical proton or carbon ion therapy treatment plan generates an approximately uniform thermal neutron field within the target volume, centred around the beam path. The tissue concentrations of neutron capture agents required to obtain an arbitrary 10% increase in biological effective dose are estimated for realistic treatment plans, and compared to concentrations previously reported in the literature. We conclude that the proposed method is theoretically feasible, and can provide a worthwhile improvement in the dose delivered to the tumour relative to healthy tissue with readily achievable concentrations of neutron capture enhancement drugs. © 2024 The Authors published by Springer Nature Limited. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.