Search

This paper reports on the design of an open source treatment planning system for optimal multi-ion irradiation of a heterogeneous target with arbitrary spatial dose distributions. The developed TPS features controllable avoidance of dose in organs at risk and optional linear energy transfer enhancement in hypoxic target sub-volumes. The performance of the treatment planning system is evaluated under a variety of conditions in a heterogeneous target to demonstrate the dose uniformity and conformance benefits of treatment achievable with manifold multi-ion therapy versus single-ion or dual-ion therapy.

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.

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 urn:x-wiley:00942405:media:mp14177:mp14177-math-0001C at 350 MeV/u, urn:x-wiley:00942405:media:mp14177:mp14177-math-0002O at 250 MeV/u, urn:x-wiley:00942405:media:mp14177:mp14177-math-0003C at 350 MeV/u, and urn:x-wiley:00942405:media:mp14177:mp14177-math-0004O 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 urn:x-wiley:00942405:media:mp14177:mp14177-math-0005 was 1.2 ± 0.1 for both urn:x-wiley:00942405:media:mp14177:mp14177-math-0006C and urn:x-wiley:00942405:media:mp14177:mp14177-math-0007C beams, while for urn:x-wiley:00942405:media:mp14177:mp14177-math-0008O and urn:x-wiley:00942405:media:mp14177:mp14177-math-0009O it was 1.4 ± 0.1 and 1.3 ± 0.1, respectively. At the Bragg peak, the urn:x-wiley:00942405:media:mp14177:mp14177-math-0010 was 2.7 ± 0.4 for urn:x-wiley:00942405:media:mp14177:mp14177-math-0011C and 2.9 ± 0.4 for urn:x-wiley:00942405:media:mp14177:mp14177-math-0012C, while for urn:x-wiley:00942405:media:mp14177:mp14177-math-0013O and urn:x-wiley:00942405:media:mp14177:mp14177-math-0014O it was 2.7 ± 0.4 and 2.8 ± 0.4, respectively. In the tail region, urn:x-wiley:00942405:media:mp14177:mp14177-math-0015 could only be evaluated for carbon; the urn:x-wiley:00942405:media:mp14177:mp14177-math-0016 was 1.6 ± 0.2 and 1.5 ± 0.1 for urn:x-wiley:00942405:media:mp14177:mp14177-math-0017C and urn:x-wiley:00942405:media:mp14177:mp14177-math-0018C, 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 urn:x-wiley:00942405:media:mp14177:mp14177-math-0019O and urn:x-wiley:00942405:media:mp14177:mp14177-math-0020C images compared with the values obtained for urn:x-wiley:00942405:media:mp14177:mp14177-math-0021O and urn:x-wiley:00942405:media:mp14177:mp14177-math-0022C, respectively. The difference between the depth of maximum dose and the depth of maximum positron annihilation density is 2.4 ± 0.8 mm for urn:x-wiley:00942405:media:mp14177:mp14177-math-0023C, compared to −5.6 ± 0.8 mm for urn:x-wiley:00942405:media:mp14177:mp14177-math-0024C and 0.9 ± 0.8 mm for urn:x-wiley:00942405:media:mp14177:mp14177-math-0025O vs −6.6 ± 0.8 mm for urn:x-wiley:00942405:media:mp14177:mp14177-math-0026O. Conclusions The urn:x-wiley:00942405:media:mp14177:mp14177-math-0027 values for urn:x-wiley:00942405:media:mp14177:mp14177-math-0028C and urn:x-wiley:00942405:media:mp14177:mp14177-math-0029O 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, urn:x-wiley:00942405:media:mp14177:mp14177-math-0030C and urn:x-wiley:00942405:media:mp14177:mp14177-math-0031O beams produce much better quality images for range verification compared with urn:x-wiley:00942405:media:mp14177:mp14177-math-0032C and urn:x-wiley:00942405:media:mp14177:mp14177-math-0033O, in particular with regard to estimating the location of the Bragg peak.

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 prompt gamma photons with energies of 478 keV (10B) or 7.94 MeV (157Gd). 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. The majority of photons resulting from neutron capture were found to arrive at the detector at least 60 ns later than photons created by other processes. 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.

This work presents a simulation study evaluating relative biological effectiveness at 10% survival fraction (RBE10) of several different positron-emitting radionuclides in heavy ion treatment systems, and comparing these to the RBE10s of their non-radioactive counterparts. RBE10 is evaluated as a function of depth for three positron-emitting radioactive ion beams (10C, 11C and 15O) and two stable ion beams (12C and 16O) using the modified microdosimetric kinetic model (MKM) in a heterogeneous skull phantom subject to a rectangular 50 mm × 50 mm × 60 mm spread out Bragg peak. We demonstrate that the RBE10 of the positron-emitting radioactive beams is almost identical to the corresponding stable isotopes. The potential improvement in PET quality assurance image quality which is obtained when using radioactive beams is evaluated by comparing the signal to background ratios of positron annihilations at different intra- and post-irradiation time points. Finally, the incidental dose to the patient resulting from the use of radioactive beams is also quantified and shown to be negligible.

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 11 C at 350 MeV/u, 15 O at 250 MeV/u, 12 C at 350 MeV/u, and 16 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 h b o x RBE 10 was 1.2 ± 0.1 for both 11 C and 12 C beams, while for 15 O and 16 O it was 1.4 ± 0.1 and 1.3 ± 0.1, respectively. At the Bragg peak, the RBE 10 was 2.7 ± 0.4 for 11 C and 2.9 ± 0.4 for 12 C, while for 15 O and 16 O it was 2.7 ± 0.4 and 2.8 ± 0.4, respectively. In the tail region, RBE 10 could only be evaluated for carbon; the RBE 10 was 1.6 ± 0.2 and 1.5 ± 0.1 for 11 C and 12 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 15 O and 11 C images compared with the values obtained for 16 O and 12 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 11 C, compared to -5.6 ± 0.8 mm for 12 C and 0.9 ± 0.8 mm for 15 O vs -6.6 ± 0.8 mm for 16 O. Conclusions The RBE 10 values for 11 C and 15 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, 11 C and 15 O beams produce much better quality images for range verification compared with 12 C and 16 O, in particular with regard to estimating the location of the Bragg peak.

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

High-resolution arrays of discrete monocrystalline scintillators used for gamma photon coincidence detection in PET are costly and complex to fabricate, and exhibit intrinsically non-uniform sensitivity with respect to emission angle. Nanocomposites and transparent ceramics are two alternative classes of scintillator materials which can be formed into large monolithic structures, and which, when coupled to optical photodetector arrays, may offer a pathway to low cost, high-sensitivity, high-resolution PET. However, due to their high optical attenuation and scattering relative to monocrystalline scintillators, these materials exhibit an inherent trade-off between detection sensitivity and the number of scintillation photons which reach the optical photodetectors. In this work, a method for optimising scintillator thickness to maximise the probability of locating the point of interaction of 511 keV photons in a monolithic scintillator within a specified error bound is proposed and evaluated for five nanocomposite materials (LaBr3:Ce-polystyrene, Gd2O3-polyvinyl toluene, LaF3:Ce-polystyrene, LaF3:Ce-oleic acid and YAG:Ce-polystyrene) and four ceramics (GAGG:Ce, GLuGAG:Ce, GYGAG:Ce and LuAG:Pr). LaF3:Ce-polystyrene and GLuGAG:Ce were the best-performing nanocomposite and ceramic materials, respectively, with maximum sensitivities of 48.8% and 67.8% for 5 mm localisation accuracy with scintillator thicknesses of 42.6 mm and 27.5 mm, respectively.

With the increase in complexity of brachytherapy treatments, there has been a demand for the development of sophisticated devices for delivery verification. The Centre for Medical Radiation Physics (CMRP), University of Wollongong, has demonstrated the applicability of semiconductor devices to provide cost-effective real-time quality assurance for a wide range of brachytherapy treatment modalities. Semiconductor devices have shown great promise to the future of pretreatment and in vivo quality assurance in a wide range of brachytherapy treatments, from high-dose-rate (HDR) prostate procedures to eye plaque treatments. The aim of this article is to give an insight into several semiconductor-based dosimetry instruments developed by the CMRP. Applications of these instruments are provided for breast and rectal wall in vivo dosimetry in HDR brachytherapy, urethral in vivo dosimetry in prostate low-dose-rate (LDR) brachytherapy, quality assurance of HDR brachytherapy afterloaders, HDR pretreatment plan verification, and real-time verification of LDR and HDR source dwell positions.

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.

Purpose BrachyView is a novel in-body imaging system which aims to provide LDR brachytherapy seeds position reconstruction within the prostate in real-time. The first prototype is presented in this study: the probe consists of a gamma camera featuring three single cone pinhole collimators embedded in a tungsten tube, above three, high resolution pixelated detectors (Timepix). Methods The prostate was imaged with a TRUS system using a sagittal crystal with a 2.5 mm slice thickness. Eleven needles containing a total of thirty 0.508 U125I seeds were implanted under ultrasound guidance. A CT scan was used to localise the seed positions, as well as provide a reference when performing the image co-registration between the BrachyView coordinate system and the TRUS coordinate system. An in-house visualisation software interface was developed to provide a quantitative 3D reconstructed prostate based on the TRUS images and co-registered with the LDR seeds in situ. A rigid body image registration was performed between the BrachyView and TRUS systems, with the BrachyView and CT-derived source locations compared. Results The reconstructed seed positions determined by the BrachyView probe showed a maximum discrepancy of 1.78 mm, with 75% of the seeds reconstructed within 1 mm of their nominal location. An accurate co-registration between the BrachyView and TRUS coordinate system was established. Conclusions The BrachyView system has shown its ability to reconstruct all implanted LDR seeds within a tissue equivalent prostate gel phantom, providing both anatomical and seed position information in a single interface.

© 2019 IEEE. 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.

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 [Formula: see text]-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.

The choice of pinhole geometry is a critical factor in the performance of pinhole-collimator-based source tracking systems for brachytherapy QA. In this work, an analytical model describing the penetrative sensitivity of a single-cone pinhole collimator to photons emitted from a point source is derived. Using existing models for single-cone resolution and double-cone sensitivity and resolution, the theoretical sensitivity and resolution of the single-cone collimator are quantitatively compared with those of a double-cone collimator with an equivalent field of view. Monte Carlo simulations of the single and double-cone pinhole collimators using an accurate 3D model of a commercial high dose rate brachytherapy source are performed to evaluate the relative performance of each geometry for a novel real-time HDR brachytherapy QA system, H DR BrachyView. The theoretical penetrative sensitivity of the single-cone pinhole is shown to be higher than the double-cone pinhole, which is in agreement with the results from the Monte Carlo simulations. The wider pinhole response function of the single-cone collimator results in a larger total error between the projected center of the source and the estimated center of mass of the source projection for the single-cone collimator, with the greatest error (at the maximum FoV angle) being 0.54 mm for the double-cone pinhole and 1.37 mm for the single-cone at $\theta ={ 60^ \circ }$ . The double-cone pinhole geometry is determined to be the most appropriate choice for the pinhole collimator in the H DR BrachyView probe.

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.

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.

Purpose: This paper presents initial experimental results from a prototype of high dose rate (HDR) BrachyView, a novel in-body source tracking system for HDR brachytherapy based on a multipinhole tungsten collimator and a high resolution pixellated silicon detector array. The probe and its associated position estimation algorithms are validated and a comprehensive evaluation of the accuracy of its position estimation capabilities is presented. Methods: The HDR brachytherapy source is moved through a sequence of positions in a prostate phantom, for various displacements in x, y, and z. For each position, multiple image acquisitions are performed, and source positions are reconstructed. Error estimates in each dimension are calculated at each source position and combined to calculate overall positioning errors. Gafchromic film is used to validate the accuracy of source placement within the phantom. Results: More than 90% of evaluated source positions were estimated with an error of less than one millimeter, with the worst-case error being 1.3 mm. Experimental results were in close agreement with previously published Monte Carlo simulation results. Conclusions: The prototype of HDR BrachyView demonstrates a satisfactory level of accuracy in its source position estimation, and additional improvements are achievable with further refinement of HDR BrachyView’s image processingmore » algorithms.« less

BrachyView is a novel in-body imaging system for real-time intraoperative prostate brachytherapy treatment planning, which monitors the position of low dose rate brachytherapy seeds using an array of high-resolution pixelated silicon detectors (Timepix). The detector array is also capable of performing in-body imaging of the prostate when used in conjunction with an external X-ray source. This study presents a quantitative analysis of the Timepix detector for use as a soft-tissue imaging plane by evaluating varying thicknesses of tissue-equivalent plastic incorporated into a medical prostate phantom. The feasibility of using BrachyView as a diagnostic tool is established by demonstrating the resolving power and high contrast obtainable with this configuration.

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 $\beta^{+}$-activation of tissue during treatment. Predictions of these $\beta^{+}$-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.

© 2019 Commonwealth of Australia, Australian Nuclear Science and Technology Organisation, ANSTO.. 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.

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.

Parallax error caused by the detector crystal thickness degrades spatial resolution at the peripheral regions of the field-of-view (FOV) of a scanner. To resolve this issue, depth-of-interaction (DOI) measurement is a promising solution to improve the spatial resolution and its uniformity over the entire FOV. Even though DOI detectors have been used in dedicated systems with a small ring diameter such as for the human brain, breast and small animals, the use of DOI detectors for a large bore whole-body PET system has not been demonstrated yet. We have developed a four-layered DOI detector, and its potential for a brain dedicated system has been proven in our previous development. In the present work, we investigated the use of the four-layer DOI detector for a large bore PET system by developing the world's first whole-body prototype. We evaluated its performance characteristics in accordance with the NEMA NU 2 standard. Furthermore, the impact of incorporating DOI information was evaluated with the NEMA NU 4 image quality phantom. Point source images were reconstructed with a filtered back projection (FBP), and an average spatial resolution of 5.2 ± 0.7 mm was obtained. For the FBP image, the four-layer DOI information improved the radial spatial resolution by 48% at the 20 cm offset position. The peak noise-equivalent count rate (NECR) was 22.9 kcps at 7.4 kBq ml-1 and the scatter fraction was 44%. The system sensitivity was 5.9 kcps MBq-1. For the NEMA NU 2 image quality phantom, the 10 mm sphere was clearly visualized without any artifacts. For the NEMA NU 4 image quality phantom, we measured the phantom at 0, 10 and 20 cm offset positions. As a result, we found the image with four-layer DOI could visualize the 2 mm-diameter hot cylinder although it could not be recognized on the image without DOI. The average improvements in the recovery coefficients for the five hot rods (1-5 mm) were 0.3%, 4.4% and 26.3% at the 0, 10 and 20 cm offset positions, respectively (except for the 1 mm-diameter rod at the 20 cm offset position). Although several practical issues (such as adding end-shields) remain to be addressed before the scanner is ready for clinical use, we showed that the four-layer DOI technology provided higher and more uniform spatial resolution over the FOV and improved contrast for small uptake regions located at the peripheral FOV, which could improve detectability of small and distal lesions such as nodal metastases, especially in obese patients.

© 2018 Commonwealth of Australia. Department of Education and Training, and Department of Industry, Innovation and Science.. This paper presents a simulation study of BrachyShade, a proposed internal source-tracking system for real time quality assurance in high dose rate prostate brachytherapy. BrachyShade consists of a set of spherical tungsten occluders located above a pixellated silicon photodetector. The source location is estimated by minimising the mean squared error between a parametric model of the shadow image and acquired images of the shadows projected on the detector plane. A novel algorithm is finally employed to correct the systemic error resulting from Compton scattering in the medium. The worst-case error obtained with BrachyShade for a 13.5 ms image acquisition is less than 1.3 mm in the most distant part of the treatment volume, while for 75% of source locations an error of less than 0.42 mm was achieved.

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 μs and a total detector capacitance of 2pF. The energy resolution obtained at room temperature (21 ° 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. © 2006 IEEE.

© 2015 Institute of Physics and Engineering in Medicine. A common approach to improving the spatial resolution of small animal PET scanners is to reduce the size of scintillation crystals and/or employ high resolution pixellated semiconductor detectors. The large number of detector elements results in the system matrix - an essential part of statistical iterative reconstruction algorithms - becoming impractically large. In this paper, we propose a methodology for system matrix modelling which utilises a virtual single-layer detector ring to greatly reduce the size of the system matrix without sacrificing precision. Two methods for populating the system matrix are compared; the first utilises a geometrically-derived system matrix based on Siddon's ray tracer method with the addition of an accurate detector response function, while the second uses Monte Carlo simulation to populate the system matrix. The effectiveness of both variations of the proposed technique is demonstrated via simulations of PETiPIX, an ultra high spatial resolution small animal PET scanner featuring high-resolution DoI capabilities, which has previously been simulated and characterised using classical image reconstruction methods. Compression factors of and are achieved using this methodology for the system matrices produced using the geometric and Monte Carlo-based approaches, respectively, requiring a total of 0.5-1.2 GB of memory-resident storage. Images reconstructed from Monte Carlo simulations of various point source and phantom models, produced using system matrices generated via both geometric and simulation methods, are used to evaluate the quality of the resulting system matrix in terms of achievable spatial resolution and the CRC, CoV and CW-SSIM index image quality metrics. The Monte Carlo-based system matrix is shown to provide the best image quality at the cost of substantial one-off computational effort and a lower (but still practical) compression factor. Finally, a straightforward extension of the virtual ring method to a three dimensional virtual cylinder is demonstrated using a 3D DoI PET scanner.

© 2014 Institute of Physics and Engineering in Medicine. HDR BrachyView is a novel in-body dosimetric imaging system for real-time monitoring and verification of the source position in high dose rate (HDR) prostate brachytherapy treatment. It is based on a high-resolution pixelated detector array with a semi-cylindrical multi-pinhole tungsten collimator and is designed to fit inside a compact rectal probe, and is able to resolve the 3D position of the source with a maximum error of 1.5 mm. This paper presents an evaluation of the additional dose that will be delivered to the patient as a result of backscatter radiation from the collimator. Monte Carlo simulations of planar and cylindrical collimators embedded in a tissue-equivalent phantom were performed using Geant4, with an 192Ir source placed at two different source-collimator distances. The planar configuration was replicated experimentally to validate the simulations, with a MOSkin dosimetry probe used to measure dose at three distances from the collimator. For the cylindrical collimator simulation, backscatter dose enhancement was calculated as a function of axial and azimuthal displacement, and dose distribution maps were generated at three distances from the collimator surface. Although significant backscatter dose enhancement was observed for both geometries immediately adjacent to the collimator, simulations and experiments indicate that backscatter dose is negligible at distances beyond 1 mm from the collimator. Since HDR BrachyView is enclosed within a 1 mm thick tissue-equivalent plastic shell, all backscatter radiation resulting from its use will therefore be absorbed before reaching the rectal wall or other tissues. dosimetry, brachytherapy, HDR

BrachyView is a novel in-body imaging system utilising high-resolution pixelated silicon detectors (Timepix) and a pinhole collimator for brachytherapy source localisation. Recent studies have investigated various options for real-time intraoperative dynamic dose treatment planning to increase the quality of implants. In a previous proof-of-concept study, the justification of the pinhole concept was shown, allowing for the next step whereby multiple active seeds are implanted into a PMMA phantom to simulate a more realistic clinical scenario. In this study, 20 seeds were implanted and imaged using a lead pinhole of 400 μ m diameter. BrachyView was able to resolve the seed positions within 1–2 mm of expected positions, which was verified by co-registering with a full clinical post-implant CT scan.

The purpose of this study was to investigate a compact readout for silicon photomultiplier (SiPM) array in the development of high-resolution imaging detector to reduce the readout channels while maximizing the detectors performance. The detector module was composed of a L YSO scintillation crystal array and a SensL's SPMArray4. The crystal array was coupled to the SiPM array with a 2mm-thick silicone pad to improve the light sharing among the SiPM array elements. Three LYSO crystal arrays of 4×4, 8×8 and 12×12 crystal elements with pixel sizes of 3.2, 1.6 and 1.0 mm were investigated in this study. Two compact multiplexed readouts based on the light sharing principle have been developed to reduce the detectors readout channels from 16 to 4 outputs while achieving a maximized performance in its spatial resolution. One is based on a conventional charge division method which was utilized with a discretized positioning circuit (DPC). The other is based on a novel two-stage charge division which was utilized with a symmetric charge division circuit to divide the charges from 16 SiPM elements into a 4-row and 4-column resistive network and then used a subtractive readout circuit to further reduce the readout channels from 8 to 4 outputs. The performance of the detector module with two compact multiplexed readouts was evaluated with L YSO arrays with different crystal sizes using a 137CS point source. The preliminary results show that both compact multiplexed readouts can provide very good spatial resolution with good uniformity and resolve up to 1mm pixel elements of LYSO arrays. The compact readout based on the two-stage charge division with subtractive resistive-readout shows a slightly better improvement in the crystal identification while reducing the non-linearity of the flood image as compared to the DPC readout. In conclusion, both compact multiplexed readouts are effective approaches for the development of high-resolution detector module for compact micro-PET.

A novel high resolution PET scanner dedicated to imaging small volumes (small animals or positron mammography) has been developed. The system utilises a novel SiPM detector array coupled to a pixelated LYSO scintillator and placed in an edge-on formation around the ring. The unique design provides a more accurate placement of the Lines of Response (LoR) by measuring the Depth of Interaction (DoI) which results in a uniform spatial resolution across the whole field of view (FoV). Analytical modelling of the effect of parallax error on spatial resolution is presented. A full prototype of the system is simulated using GATE/GEANT4 with Ge-68 point sources placed at various positions within the FoV. The simulation results are compared to experimental measurements on the prototype system, and the effectiveness of the proposed approach to determining the DoI is demonstrated. The effectiveness of the DoI estimation in achieving a uniform spatial resolution across the entire FoV is demonstrated where a 30% improvement in spatial resolution close to the outer edge of the gantry ring is obtained. Preliminary images of a micro-Defrise phantom filled with F-18 obtained using the prototype system are presented and compared with a simulation of the same configuration. © 2011 IEEE.

A novel detector module configuration based on silicon photomultiplier (SiPM) detectors with LYSO scintillators, a multichannel mixed analog/digital ASIC and an FPGA-based digital data acquisition system has been developed for preclinical positron emission tomography (PET). The SCEPTER ASIC, originally developed for soft X-ray detection at Brookhaven National Laboratory, has a unique architecture incorporating multiple peak detectors and time-to-amplitude converters, and offers an extremely low dead time, making it ideal for coincidence detection. A representative pair of channels in the prototype system has been characterised. Measured energy and timing resolutions are reported for coincidences between a singlepixel SiPM detector and a conventional PMT. A timing resolution of 11.7 ns was achieved during a 48 hour run. Energy resolution for the SiPM device and data acquisition system was found to be 17%.

PETiPIX is an ultra high spatial resolution positron emission tomography (PET) scanner designed for imaging mice brains. Four Timepix pixellated silicon detector modules are placed in an edge-on configuration to form a scanner with a field of view (FoV) 15 mm in diameter. Each detector module consists of 256 × 256 pixels with dimensions of 55 × 55 × 300 μm3. Monte Carlo simulations using GEANT4 Application for Tomographic Emission (GATE) were performed to evaluate the feasibility of the PETiPIX design, including estimation of system sensitivity, angular dependence, spatial resolution (point source, hot and cold phantom studies) and evaluation of potential detector shield designs. Initial experimental work also established that scattered photons and recoil electrons could be detected using a single edge-on Timepix detector with a positron source. Simulation results estimate a spatial resolution of 0.26 mm full width at half maximum (FWHM) at the centre of FoV and 0.29 mm FWHM overall spatial resolution with sensitivity of 0.01%, and indicate that a 1.5 mm thick tungsten shield parallel to the detectors will absorb the majority of non-coplanar annihilation photons, significantly reducing the rates of randoms. Results from the simulated phantom studies demonstrate that PETiPIX is a promising design for studies demanding high resolution images of mice brains.

Purpose: High dose rate (HDR) brachytherapy is a form of radiation therapy for treating prostate cancer whereby a high activity radiation source is moved between predefined positions inside applicators inserted within the treatment volume. Accurate positioning of the source is essential in delivering the desired dose to the target area while avoiding radiation injury to the surrounding tissue. In this paper, HDR BrachyView, a novel inbody dosimetric imaging system for real time monitoring and verification of the radioactive seed position in HDR prostate brachytherapy treatment is introduced. The current prototype consists of a 15 Multiplication-Sign 60 mm{sup 2} silicon pixel detector with a multipinhole tungsten collimator placed 6.5 mm above the detector. Seven identical pinholes allow full imaging coverage of the entire treatment volume. The combined pinhole and pixel sensor arrangement is geometrically designed to be able to resolve the three-dimensional location of the source. The probe may be rotated to keep the whole prostate within the transverse plane. The purpose of this paper is to demonstrate the efficacy of the design through computer simulation, and to estimate the accuracy in resolving the source position (in detector plane and in 3D space) as part of the feasibility study for themore » BrachyView project.Methods: Monte Carlo simulations were performed using the GEANT4 radiation transport model, with a {sup 192}Ir source placed in different locations within a prostate phantom. A geometrically accurate model of the detector and collimator were constructed. Simulations were conducted with a single pinhole to evaluate the pinhole design and the signal to background ratio obtained. Second, a pair of adjacent pinholes were simulated to evaluate the error in calculated source location.Results: Simulation results show that accurate determination of the true source position is easily obtainable within the typical one second source dwell time. The maximum error in the estimated projection position was found to be 0.95 mm in the imaging (detector) plane, resulting in a maximum source positioning estimation error of 1.48 mm.Conclusions: HDR BrachyView is a feasible design for real-time source tracking in HDR prostate brachytherapy. It is capable of resolving the source position within a subsecond dwell time. In combination with anatomical information obtained from transrectal ultrasound imaging, HDR BrachyView adds a significant quality assurance capability to HDR brachytherapy treatment systems.« less

Purpose: The conformity of the achieved dose distribution to the treatment plan strongly correlates with the accuracy of seed implantation in a prostate brachytherapy treatment procedure. Incorrect seed placement leads to both short and long term complications, including urethral and rectal toxicity. The authors present BrachyView, a novel concept of a fast intraoperative treatment planning system, to provide real-time seed placement information based on in-body gamma camera data. BrachyView combines the high spatial resolution of a pixellated silicon detector (Medipix2) with the volumetric information acquired by a transrectal ultrasound (TRUS). The two systems will be embedded in the same probe so as to provide anatomically correct seed positions for intraoperative planning and postimplant dosimetry. Dosimetric calculations are based on the TG-43 method using the real position of the seeds. The purpose of this paper is to demonstrate the feasibility of BrachyView using the Medipix2 pixel detector and a pinhole collimator to reconstruct the real-time 3D position of low dose-rate brachytherapy seeds in a phantom. Methods: BrachyView incorporates three Medipix2 detectors coupled to a multipinhole collimator. Three-dimensionally triangulated seed positions from multiple planar images are used to determine the seed placement in a PMMA prostate phantom in real time. MATLAB codesmore » were used to test the reconstruction method and to optimize the device geometry. Results: The results presented in this paper show a 3D position reconstruction accuracy of the seed in the range of 0.5-3 mm for a 10-60 mm seed-to-detector distance interval (Z direction), respectively. The BrachyView system also demonstrates a spatial resolution of 0.25 mm in the XY plane for sources at 10 mm distance from Medipix2 detector plane, comparable to the theoretical value calculated for an equivalent gamma camera arrangement. The authors successfully demonstrated the capability of BrachyView for real-time imaging (using a 3 s data acquisition time) of different brachytherapy seed configurations (with an activity of 0.05 U) throughout a 60 Multiplication-Sign 60 Multiplication-Sign 60 mm{sup 3} Perspex prostate phantom. Conclusions: The newly developed miniature gamma camera component of BrachyView, with its high spatial resolution and real time capability, allows accurate 3D localization of seeds in a prostate phantom. Combination of the gamma camera with TRUS in a single probe will complete the BrachyView system.« less