A quantitative assessment of Geant4 for predicting the yield and distribution of positron-emitting fragments in ion beam therapy.

PURPOSE: To compare the accuracy with which different hadronic inelastic physics models across ten Geant4 Monte Carlo simulation toolkit versions can predict positron-emitting fragments produced along the beam path during carbon and oxygen ion therapy. Materials and Methods: Phantoms of polyethylene, gelatin or poly(methyl methacrylate) were irradiated with monoenergetic carbon and oxygen ion beams. Post-irradiation, 4D PET images were acquired and parent11C,10C and15O radionuclides contributions in each voxel were determined from the extracted time activity curves. Next, the experimental configurations were simulated in Geant4 Monte Carlo versions 10.0 to 11.1, with three different fragmentation models - binary ion cascade (BIC), quantum molecular dynamics (QMD) and the Liege intranuclear cascade (INCL++) - 30 model-version combinations. Total positron annihilation and parent isotope production yields predicted by each simulation were compared between simulations and experiments using normalised mean squared error and Pearson cross-correlation coefficient. Finally, we compared the depth of maximum positron annihilation yield and the distal point at which positron yield decreases to 50% of peak between each model and the experimental results. Results: Performance varied considerably across versions and models, with no one version/model combination providing the best prediction of all positron-emitting fragments in all evaluated target materials and irradiation conidiations. BIC in Geant4 10.2 provided the best overall agreement with experimental results in the largest number of test cases. QMD consistently provided the best estimates of both the depth of peak positron yield (10.4 and 10.6) and the distal 50%-of-peak point (10.2), while BIC also performed well and INCL generally performed the worst across most Geant4 versions. Conclusions: Best spatial prediction of annihilation yield and positron-emitting fragment production during carbon and oxygen ion therapy was found to be 10.2.p03 with BIC or QMD. These version/model combinations are recommended for future heavy ion therapy research.

Feasibility Study for a Microstrip Transmission Line RF Coil Integrated with a PET Detector Module in a 7T Human MR Imaging System.

PURPOSE: The purpose of this study was to do a feasibility study on a microstrip transmission line (MS) RF coil for a positron emission tomography (PET) insert in a 7 Tesla human MRI system. The proposed MS coil integrated the RF shield of the PET detector as the ground conductor of the coil. We called the integrated module "MS PET coil." METHODS: A single-channel MS PET coil was developed with an integrated RF-shielded PET detector module. For comparison, we also studied a conventional MS coil with a single-layer ground conductor. A lutetium fine silicate (LFS) scintillation crystal block (14 × 14 × 4-layer) with a silicon photomultiplier (Hamamatsu Photonics K.K., Shizuoka, Japan) and a front-end readout circuit board were mounted inside the shield cage of the MS PET coil. The MS PET coil was studied with and without PET detectors. All three coil configurations were studied with a homogeneous phantom in a 7T MRI system (Siemens Healthineers, Erlangen, Germany). PET data measurements were conducted using a Cesium-137 radiation point source. RESULTS: The MR images were similar for the MS coil and the empty MS PET coil, as well as for the cases of MS PET coil with and without PET measurements. Compared to the empty MS PET coil (without PET detector and cable RF shield), decreases in SNR, increases in image noise and RF power, and a slight decrease in resonance frequency were seen for the case of the MS PET coil with the detector and cable shield. Differences in the PET energy histograms or in the crystal identification maps with and without MRI measurements were negligible. CONCLUSIONS: Both the MRI and PET performances of the MS PET coil showed responses that matched the MS coil responses. The performance variations of MRI data with and without PET measurement and PET data with and without MR imaging were negligible.

Study on the radiofrequency transparency of partial-ring oval-shaped prototype PET inserts in a 3 T clinical MRI system.

The purpose of this study is to evaluate the RF field responses of partial-ring RF-shielded oval-shaped positron emission tomography (PET) inserts that are used in combination with an MRI body RF coil. Partial-ring PET insert is particularly suitable for interventional investigation (e.g., trimodal PET/MRI/ultrasound imaging) and intraoperative (e.g., robotic surgery) PET/MRI studies. In this study, we used electrically floating Faraday RF shield cages to construct different partial-ring configurations of oval and cylindrical PET inserts and performed experiments on the RF field, spin echo and gradient echo images for a homogeneous phantom in a 3 T clinical MRI system. For each geometry, partial-ring configurations were studied by removing an opposing pair or a single shield cage from different positions of the PET ring. Compared to the MRI-only case, reduction in mean RF homogeneity, flip angle, and SNR for the detector opening in the first and third quadrants was approximately 13%, 15%, and 43%, respectively, whereas the values were 8%, 23%, and 48%, respectively, for the detector openings in the second and fourth quadrants. The RF field distribution also varied for different partial-ring configurations. It can be concluded that the field penetration was high for the detector openings in the first and third quadrants of both the inserts.

MRI compatibility study of a prototype radiofrequency penetrable oval PET insert at 3 T.

PURPOSE: To perform an MRI compatibility study of an RF field-penetrable oval-shaped PET insert that implements an MRI built-in body RF coil both as a transmitter and a receiver. METHODS: Twelve electrically floating RF shielded PET detector modules were used to construct the prototype oval PET insert with a major axis of 440 mm, a minor axis of 350 mm, and an axial length of 225 mm. The electric floating of the PET detector modules was accomplished by isolating the cable shield from the detector shield using plastic tape. Studies were conducted on the transmit (B1) RF field, the image signal-to-noise ratio (SNR), and the RF pulse amplitude for a homogeneous cylindrical (diameter: 160 mm and length: 260 mm) phantom (NaCl + NiSO4 solution) in a 3 T clinical MRI system (Verio, Siemens, Erlangen, Germany). RESULTS: The B1 maps for the oval insert were similar to the MRI-only field responses. Compared to the MRI-only values, SNR reductions of 51%, 45%, and 59% were seen, respectively, for the spin echo (SE), gradient echo (GE), and echo planar (EPI) images for the case of oval PET insert. Moreover, the required RF pulse amplitudes for the SE, GE, and EPI sequences were, respectively, 1.93, 1.85, and 1.36 times larger. However, a 30% reduction in the average RF reception sensitivity was observed for the oval insert. CONCLUSIONS: The prototype floating PET insert was a safety concern for the clinical MRI system, and this compatibility study provided clearance for developing a large body size floating PET insert for the existing MRI system. Because of the RF shield of the insert, relatively large RF powers compared to the MRI-only case were required. Because of this and also due to low RF sensitivity of the body coil, the SNRs reduced largely.

Imaging assessment of photosensitizer emission induced by radionuclide-derived Cherenkov radiation using charge-coupled device optical imaging and long-pass filters.

BACKGROUND: Radionuclides produce Cherenkov radiation (CR), which can potentially activate photosensitizers (PSs) in phototherapy. Several groups have studied Cherenkov energy transfer to PSs using optical imaging; however, cost-effectively identifying whether PSs are excited by radionuclide-derived CR and detecting fluorescence emission from excited PSs remain a challenge. Many laboratories face the need for expensive dedicated equipment. AIM: To cost-effectively confirm whether PSs are excited by radionuclide-derived CR and distinguish fluorescence emission from excited PSs. METHODS: The absorbance and fluorescence spectra of PSs were measured using a microplate reader and fluorescence spectrometer to examine the photo-physical properties of PSs. To mitigate the need for expensive dedicated equipment and achieve the aim of the study, we developed a method that utilizes a charge-coupled device optical imaging system and appropriate long-pass filters of different wavelengths (manual sequential application of long-pass filters of 515, 580, 645, 700, 750, and 800 nm). Tetrakis (4-carboxyphenyl) porphyrin (TCPP) was utilized as a model PS. Different doses of copper-64 (64CuCl2) (4, 2, and 1 mCi) were used as CR-producing radionuclides. Imaging and data acquisition were performed 0.5 h after sample preparation. Differential image analysis was conducted by using ImageJ software (National Institutes of Health) to visually evaluate TCPP fluorescence. RESULTS: The maximum absorbance of TCPP was at 390-430 nm, and the emission peak was at 670 nm. The CR and CR-induced TCPP emissions were observed using the optical imaging system and the high-transmittance long-pass filters described above. The emission spectra of TCPP with a peak in the 645-700 nm window were obtained by calculation and subtraction based on the serial signal intensity (total flux) difference between 64CuCl2 + TCPP and 64CuCl2. Moreover, the differential fluorescence images of TCPP were obtained by subtracting the 64CuCl2 image from the 64CuCl2 + TCPP image. The experimental results considering different 64CuCl2 doses showed a dose-dependent trend. These results demonstrate that a bioluminescence imaging device coupled with different long-pass filters and subtraction image processing can confirm the emission spectra and differential fluorescence images of CR-induced TCPP. CONCLUSION: This simple method identifies the PS fluorescence emission generated by radionuclide-derived CR and can contribute to accelerating the development of Cherenkov energy transfer imaging and the discovery of new PSs.

Discrimination of inter-crystal scattering events by signal processing for the X'tal cube PET detector.

Inter-crystal scattering (ICS) events cause degradation of the contrast in PET images. We developed the X'tal cube PET detector with submillimeter spatial resolution, which consisted of a segmented LYSO scintillator and 96 MPPCs. For this high spatial resolution PET detector, the ICS event was not negligible. In this study, we proposed a method to discriminate the ICS events and showed its feasibility by the following method. For each 96 MPPC, we measured the mean and standard deviation of the peak in the pulse height distribution obtained by the photoabsorption events in a scintillator pixel. Every time a newly detected event was identified as the segment, we monitored the reduced chi-square value that was calculated with the pulse height and the prepared mean and the standard deviation for each 96 MPPC. Since the pulse height caused by the photoabsorption event resulted in a small reduced chi-square value, we could eliminate the ICS events by setting a threshold on the reduced chi-square value. We carried out both a Monte Carlo simulation and a scanning experiment. By the simulation, we confirmed that the threshold of the reduced chi square significantly discriminated the ICS event. We obtained the response function by a scanning experiment with a 0.2 mm slit beam of 511 keV gamma-ray. The standard deviation of the response function was improved from 1.6 to 1.06 mm by eliminating the ICS events. The proposed method could significantly eliminate the ICS events and retain the true events.

Optimum selection for multi-interaction events in Compton-PET hybrid reconstruction: a Monte Carlo study.

In Compton PET, that has a scatterer inserted inside a PET ring, there are multi-interaction events that can be treated as both PET and Compton events. A PET event from multi-interaction events that include a Compton event and a photoelectric absorption event or two Compton events can be extracted by applying a PET recovery method. In this study, we aimed to establish a method to maximize image quality by utilizing such redundant events. We conducted brain-scale Monte Carlo simulations of a C-shaped Compton-PET geometry and a whole gamma imaging (WGI) geometry. Images were reconstructed by a hybrid image reconstruction method combining both PET and Compton events. The result showed that the spatial resolution was improved when treated as PET events while keeping the noise level. The effect of improvement was more significant in WGI than in C-shaped Compton PET because the number of events recovered as PET events having more accurate spatial information was much larger in WGI. When the PET-recovered multi-interaction events were also included as Compton events in the hybrid reconstruction, we did not observe any improvement in image quality, while the number of used events was largest. The results suggested that treating events as PET events exclusively was better for image quality.

Submillimeter-Resolution PET for High-Sensitivity Mouse Brain Imaging.

PET is a powerful molecular imaging technique that can provide functional information on living objects. However, the spatial resolution of PET imaging has been limited to around 1 mm, which makes it difficult to visualize mouse brain function in detail. Here, we report an ultrahigh-resolution small-animal PET scanner we developed that can provide a resolution approaching 0.6 mm to visualize mouse brain function with unprecedented detail. Methods: The ultrahigh-resolution small-animal PET scanner has an inner diameter of 52.5 mm and axial coverage of 51.5 mm. The scanner consists of 4 rings, each of which has 16 depth-of-interaction detectors. Each depth-of-interaction detector consists of a 3-layer staggered lutetium yttrium orthosilicate crystal array with a pitch of 1 mm and a 4 × 4 silicon photomultiplier array. The physical performance was evaluated in accordance with the National Electrical Manufacturers Association NU4 protocol. Spatial resolution was evaluated with phantoms of various resolutions. In vivo glucose metabolism imaging of the mouse brain was performed. Results: Peak absolute sensitivity was 2.84% with an energy window of 400-600 keV. The 0.55-mm rod structure of a resolution phantom was resolved using an iterative algorithm. In vivo mouse brain imaging with 18F-FDG clearly identified the cortex, thalamus, and hypothalamus, which were barely distinguishable in a commercial preclinical PET scanner that we used for comparison. Conclusion: The ultrahigh-resolution small-animal PET scanner is a promising molecular imaging tool for neuroscience research using rodent models.

Feasibility of triple gamma ray imaging of10C for range verification in ion therapy.

Objective.In carbon ion therapy, the visualization of the range of incident particles in a patient body is important for treatment verification. In-beam positron emission tomography (PET) imaging is one of the methods to verify the treatment in ion therapy due to the high quality of PET images. We have shown the feasibility of in-beam PET imaging of radioactive15O and11C ion beams for range verification using our OpenPET system. Recently, we developed a whole gamma imager (WGI) that can simultaneously work as PET, single gamma ray and triple gamma ray imaging. The WGI has high potential to detect the location of10C, which emits positrons with a simultaneous gamma ray of 718 keV, within the patient's body during ion therapy.Approach.In this work, we focus on investigating the performance of WGI for10C imaging and its feasibility for range verification in carbon ion therapy. First, the performance of the WGI was studied to image a10C point source using the Geant4 toolkit. Then, the feasibility of WGI was investigated for an irradiated polymethyl methacrylate (PMMA) phantom with a10C ion beam at the carbon therapy facility of the Heavy Ion Medical Accelerator in Chiba.Main results.The average spatial resolution and sensitivity for the simulated10C point source at the centre of the field of view were 5.5 mm FWHM and 0.010%, respectively. The depth dose of the10C ion beam was measured, and the triple gamma image of10C nuclides for an irradiated PMMA phantom was obtained by applying a simple back projection to the detected triple gammas.Significance.The shift between Bragg peak position and position of the peak of the triple gamma image in an irradiated PMMA phantom was 2.8 ± 0.8 mm, which demonstrates the capability of triple gamma imaging using WGI for range verification of10C ion beams.

Study on the radiofrequency transparency of electrically floating and ground PET inserts in a 3 T clinical MRI system.

PURPOSE: The positron emission tomography (PET) insert for a magnetic resonance imaging (MRI) system that implements the radiofrequency (RF) built-in body coil of the MRI system as a transmitter is designed to be RF-transparent, as the coil resides outside the RF-shielded PET ring. This approach reduces the design complexities (e.g., large PET ring diameter) related to implementing a transmit coil inside the PET ring. However, achieving the required field transmission into the imaging region of interest (ROI) becomes challenging because of the RF shield of the PET insert. In this study, a modularly RF-shielded PET insert is used to investigate the RF transparency considering two electrical configurations of the RF shield, namely the electrical floating and ground configurations. The purpose is to find the differences, advantages and disadvantages of these two configurations. METHODS: Eight copper-shielded PET detector modules (intermodular gap: 3 mm) were oriented cylindrically with an inner diameter of 234 mm. Each PET module included four-layer Lutetium-yttrium oxyorthosilicate scintillation crystal blocks and front-end readout electronics. RF-shielded twisted-pair cables were used to connect the front-end electronics with the power sources and PET data acquisition systems located outside the MRI room. In the ground configuration, both the detector and cable shields were connected to the RF ground of the MRI system. In the floating configuration, only the RF shields of the PET modules were isolated from the RF ground. Experiments were conducted using two cylindrical homogeneous phantoms in a 3 T clinical MRI system, in which the built-in body RF coil (a cylindrical volume coil of diameter 700 mm and length 540 mm) was implemented as a transceiver. RESULTS: For both PET configurations, the RF and MR imaging performances were lower than those for the MRI-only case, and the MRI system provided specific absorption ratio (SAR) values that were almost double. The RF homogeneity and field strength, and the signal-to-noise ratio (SNR) of the MR images were mostly higher for the floating PET configuration than they were for the ground PET configuration. However, for a shorter axial field-of-view (FOV) of 125 mm, both configurations offered almost the same performance with high RF homogeneities (e.g., 76 ± 10%). Moreover, for both PET configurations, 56 ± 6% larger RF pulse amplitudes were required for MR imaging purposes. The increased power is mostly absorbed in the conductive shields in the form of shielding RF eddy currents; as a result, the SAR values only in the phantoms were estimated to be close to the MRI-only values. CONCLUSIONS: The floating PET configuration showed higher RF transparency under all experimental setups. For a relatively short axial FOV of 125 mm, the ground configuration also performed well which indicated that an RF-penetrable PET insert with the conventional design (e.g., the ground configuration) might also become possible. However, some design modifications (e.g., a wider intermodular gap and using the RF receiver coil inside the PET insert) should improve the RF performance to the level of the MRI-only case.

Optimization of GFAG crystal surface treatment for SiPM based TOF PET detector.

Coincidence timing resolution (CTR) is an important parameter in clinical positron emission tomography (PET) scanners to increase the signal-to-noise ratio of PET images by using time-of-flight (TOF) information. Lutetium (Lu) based scintillators are often used for TOF-PET systems. However, the self-radiation of Lu-based scintillators may influence the image quality for ultra-low activity PET imaging. Recently, a gadolinium fine aluminum gallate (Ce:GFAG) scintillation crystal that features a fast decay time (∼55 ns) and no self-radiation was developed. The present study aimed at optimizing the GFAG crystal surface treatment to enhance both CTR and energy resolution (ER). The TOF-PET detector consisted of a GFAG crystal (3.0 × 3.0 × 20 mm3) and a SiPM with an effective area of 3.0 × 3.0 mm2. The timing and energy signals were extracted using a high-frequency SiPM readout circuit and then were digitized using a CAMAC DAQ system. The CTR and ER were evaluated with nine different crystal surface treatments such as partial saw-cut and chemical polishing and the 1-side saw-cut was the best choice among the treatments. The respective CTR and ER of 202 ± 2 ps and 9.5 ± 0.1% were obtained with the 1-side saw-cut; the other 5-side mechanically polished GFAG crystals had respective values which were 18 ps (9.0%) and 1.3% better than those of the all-side mechanically polished GFAG crystal. The chemically polished GFAG crystals also offered enhanced CTR and ER of about 17 ps (8.2%) and 2.1%, respectively, over the mechanically polished GFAG crystals.

Initial results of a mouse brain PET insert with a staggered 3-layer DOI detector.

Objective.Small animal positron emission tomography (PET) requires a submillimeter resolution for better quantification of radiopharmaceuticals. On the other hand, depth-of-interaction (DOI) information is essential to preserve the spatial resolution while maintaining the sensitivity. Recently, we developed a staggered 3-layer DOI detector with 1 mm crystal pitch and 15 mm total crystal thickness, but we did not demonstrate the imaging performance of the DOI detector with full ring geometry. In this study we present initial imaging results obtained for a mouse brain PET prototype developed with the staggered 3-layer DOI detector.Approach.The prototype had 53 mm inner diameter and 11 mm axial field-of-view. The PET scanner consisted of 16 DOI detectors each of which had a staggered 3-layer LYSO crystal array (4/4/7 mm) coupled to a 4 × 4 silicon photomultiplier array. The physical performance was evaluated in terms of the NEMA NU 4 2008 protocol.Main Results.The measured spatial resolutions at the center and 15 mm radial offset were 0.67 mm and 1.56 mm for filtered-back-projection, respectively. The peak absolute sensitivity of 0.74% was obtained with an energy window of 400-600 keV. The resolution phantom imaging results show the clear identification of a submillimetric rod pattern with the ordered-subset expectation maximization algorithm. The inter-crystal scatter rejection using a narrow energy window could enhance the resolvability of a 0.75 mm rod significantly.Significance.In an animal imaging experiment, the detailed mouse brain structures such as cortex and thalamus were clearly identified with high contrast. In conclusion, we successfully developed the mouse brain PET insert prototype with a staggered 3-layer DOI detector.

Development of dual-ended depth-of-interaction detectors using laser-induced crystals for small animal PET systems.

Sensitivity and spatial resolution of positron emission tomography (PET) scanners can be improved by using thicker scintillation crystals with depth-of-interaction (DOI) encoding. Subsurface laser engraving (SSLE) can be used to segment crystals of a scintillation detector in order to fabricate a DOI detector. We previously applied SSLE to crystal bars of 3 × 3 × 20 mm3and 1.5 × 1.5 × 20 mm3and developed two dual-ended detectors with DOI segments of 3 mm and 1.5 mm, respectively. To further improve the DOI resolution, our SSLE detector design can be used with smaller pitch crystal bars, making them excellent detector candidates for small animal PET scanners with submillimetre resolution. In the present study, three small crystal bars of 1 × 1 × 20 mm3, 2 × 1 × 20 mm3, and 2 × 1 × 40 mm3were laser engraved to 12, 20 and 40 segments, respectively, by applying SSLE in their height directions. The segmented crystal bars were characterised in three prototype detector arrangements. First, the 1 × 1 × 20 mm3crystal bars were characterised in an 8 × 8 crystal array designed for DOI encoding along crystal height in a conventional small animal PET design. Second, a 4 × 8 crystal array of 2 × 1 × 20 mm3crystal bars was characterised for using the DOI information for crystal interaction positioning along the axial axis of a small animal PET scanner. Finally, the third part of the study was performed on a single 2 × 1 × 40 mm3crystal bar with 40 segments to investigate the feasibility of DOI estimation in longer crystals for application in a system with extended axial length. We evaluated the capability of segment identification and energy resolution of theses detectors. The 3D position maps of the detectors were obtained using the Anger-type calculation and the crystal identification performance was evaluated for each detector. Clear segment separation was obtained for the crystal arrays with 12 (segment pitch of 1.67 mm) and 20 (segment pitch of 1 mm) segments. Mean energy resolutions of 8.8% ± 0.4% and 9.6% ± 0.8% at 511 keV were obtained for the segments in the central regions of the 8 × 8 array with 12 segments and the 4 × 8 array with 20 segments, respectively. Clear segment identification was found to be difficult for the detector with 40 segments, especially for the segments at the middle of the crystal. Energy and interaction positioning characterisation results suggest that both prototype detectors with 12 and 20 segments are well suited for small animal PET scanners with high spatial resolution.

A staggered 3-layer DOI PET detector using BaSO4reflector for enhanced crystal identification and inter-crystal scattering event discrimination capability.

The spatial resolution of small animal positron emission tomography (PET) scanners can be improved by the use of crystals with fine pitch and rejection of inter-crystal scattering (ICS) events, which leads to a better quantification of radiopharmaceuticals. On the other hand, depth-of-interaction (DOI) information is essential to preserve the spatial resolution at the PET field-of-view (FOV) periphery while keeping the sensitivity. In this study we proposed a novel staggered 3-layer DOI detector using BaSO4reflector material for an enhanced crystal identification performance as well as ICS event rejection capability over those of ESR reflector based DOI detectors. The proposed staggered 3-layer DOI detector had 3-layer staggered LYSO crystal arrays (crystal pitch = 1 mm), an acrylic light guide, and a 4 × 4 SiPM array. The 16 SiPM anode signals were read out by using a resistive network to encode the crystal position and energy information while the timing signal was extracted from the common cathode. The crystal map quality was substantially enhanced by using the BaSO4reflector material as compared to that of the ESR reflector due to the low optical crosstalk between the LYSO crystals. The ICS events can be rejected with BaSO4by using simple pulse height discrimination thanks to the light collection efficiency difference that depends on the crystal layers. As a result, the total number of events was decreased around 26% with BaSO4as compared to that of ESR. The overall energy resolution and coincidence timing resolution with BaSO4were 19.7 ± 5.6% and 591 ± 160 ps, respectively which were significantly worse than 10.9 ± 2.2% and 308 ± 23 ps values of ESR because of the relatively low light collection efficiency with BaSO4(1057 ± 308 ADC) compared to that of ESR (1808 ± 118 ADC). In conclusion, we found the proposed staggered 3-layer DOI detector using the BaSO4reflector material with ICS event rejection capability can be a cost-effective solution for realizing high resolution and highly sensitive small animal PET scanners while minimizing the complexity of the SiPM readout circuit.

A validated Geant4 model of a whole-body PET scanner with four-layer DOI detectors.

The purpose of this work is to develop a validated Geant4 simulation model of a whole-body prototype PET scanner constructed from the four-layer depth-of-interaction detectors developed at the National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Japan. The simulation model emulates the behaviour of the unique depth of interaction sensing capability of the scanner without needing to directly simulate optical photon transport in the scintillator and photodetector modules. The model was validated by evaluating and comparing performance metrics from the NEMA NU 2-2012 protocol on both the simulated and physical scanner, including spatial resolution, sensitivity, scatter fraction, noise equivalent count rates and image quality. The results show that the average sensitivities of the scanner in the field-of-view were 5.9 cps kBq-1 and 6.0 cps kBq-1 for experiment and simulation, respectively. The average spatial resolutions measured for point sources placed at several radial offsets were 5.2± 0.7 mm and 5.0± 0.8 mm FWHM for experiment and simulation, respectively. The peak NECR was 22.9 kcps at 7.4 kBq ml-1 for the experiment, while the NECR obtained via simulation was 23.3 kcps at the same activity. The scatter fractions were 44% and 41.3% for the experiment and simulation, respectively. Contrast recovery estimates performed in different regions of a simulated image quality phantom matched the experimental results with an average error of -8.7% and +3.4% for hot and cold lesions, respectively. The results demonstrate that the developed Geant4 model reliably reproduces the key NEMA NU 2-2012 performance metrics evaluated on the prototype PET scanner. A simplified version of the model is included as an advanced example in Geant4 version 10.5.

Dose quantification in carbon ion therapy using in-beam positron emission tomography.

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.

Energy spread estimation of radioactive oxygen ion beams using optical imaging.

Radioactive ion (RI) beams combined with in-beam positron emission tomography enable accuratein situbeam range verification in heavy ion therapy. However, the energy spread of the radioactive beams generated as secondary beams is wider than that of conventional stable heavy ion beams which causes Bragg peak region and distal falloff region broadening. Therefore, the energy spread of the RI beams should be measured carefully for their quality control. Here, we proposed an optical imaging technique for the energy spread estimation of radioactive oxygen ion beams. A polymethyl methacrylate phantom (10.0 × 10.0 × 9.9 cm3) was irradiated with an15O beam (mean energy = 247.7 MeV u-1, standard deviation = 6.8 MeV u-1) in the Heavy Ion Medical Accelerator in Chiba. Three different momentum acceptances of 1%, 2% and 4% were used to get energy spreads of 1.9 MeV u-1, 3.4 MeV u-1and 5.5 MeV u-1, respectively. The in-beam luminescence light and offline beam Cerenkov light images were acquired with an optical system consisting of a lens and a cooled charge-coupled device camera. To estimate the energy spread of the15O ion beams, we proposed three optical parameters: (1) distal-50% falloff length of the prompt luminescence signals; (2) full-width at half maximum of the Cerenkov light signals in the beam direction; and (3) positional difference between the peaks of the Cerenkov light and the luminescence signals. These parameters estimated the energy spread with the respective mean squared errors of 2.52 × 10-3MeV u-1, 5.91 × 10-3MeV u-1, and 0.182 MeV u-1. The distal-50% falloff length of the luminescence signals provided the lowest mean squared error among the optical parameters. From the findings, we concluded optical imaging using luminescence and Cerenkov light signals offers an accurate energy spread estimation of15O ion beams. In the future, the proposed optical parameters will be used for energy spread estimation of other RI beams as well as stable ion beams.

Experimental investigation of the characteristics of radioactive beams for heavy ion therapy.

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.

Biological washout modelling for in-beam PET: rabbit brain irradiation by 11C and 15O ion beams.

Positron emission tomography (PET) has been used for dose verification in charged particle therapy. The causes of washout of positron emitters by physiological functions should be clarified for accurate dose verification. In this study, we visualized the distribution of irradiated radioactive beams, 11C and 15O beams, in the rabbit whole-body using our original depth-of-interaction (DOI)-PET prototype to add basic data for biological washout effect correction. Time activity curves of the irradiated field and organs were measured immediately after the irradiations. All data were corrected for physical decay before further analysis. We also collected expired gas of the rabbit during beam irradiation and the energy spectrum was measured with a germanium detector. Irradiated radioactive beams into the brain were distributed to the whole body due to the biological washout process, and the implanted 11C and 15O ions were concentrated in the regions which had high blood volume. The 11C-labelled 11CO2 was detected in expired gas under the 11C beam irradiation, while no significant signal was detected under the 15O beam irradiation as a form of C15O2. Results suggested that the implanted 11C ions form molecules that diffuse out to the whole body by undergoing perfusion, then, they are incorporated into the blood-gas exchange in the respiratory system. This study provides basic data for modelling of the biological washout effect.

Influence of momentum acceptance on range monitoring of 11C and 15O ion beams using in-beam PET.

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.