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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 mm 3 ) and a SiPM with an effective area of 3.0 × 3.0 mm 2 . 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., (© 2022 IOP Publishing Ltd.)

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., (© 2021 Institute of Physics and Engineering in Medicine.)

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 mm 3 and 1.5 × 1.5 × 20 mm 3 and 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 mm 3 , 2 × 1 × 20 mm 3 , and 2 × 1 × 40 mm 3 were 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 mm 3 crystal 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 mm 3 crystal 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 mm 3 crystal 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., (© 2021 Institute of Physics and Engineering in Medicine.)

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 BaSO 4 reflector 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 BaSO 4 reflector 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 BaSO 4 by 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 BaSO 4 as compared to that of ESR. The overall energy resolution and coincidence timing resolution with BaSO 4 were 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 BaSO 4 (1057 ± 308 ADC) compared to that of ESR (1808 ± 118 ADC). In conclusion, we found the proposed staggered 3-layer DOI detector using the BaSO 4 reflector 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., (© 2021 IOP Publishing Ltd.)

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.

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 - 11 C, 10 C and 15 O. A library of basis functions is constructed by simulating a range of monoenergetic 12 C 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 12 C 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 11 C, 10 C, 15 O 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.

Radioactive ion (RI) beams combined with in-beam positron emission tomography enable accurate in situ beam 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 cm 3 ) was irradiated with an 15 O 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 -1 and 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 the 15 O 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 -3 MeV u -1 , 5.91 × 10 -3 MeV 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 of 15 O 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., (© 2020 Institute of Physics and Engineering in Medicine.)

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., (© 2020 American Association of Physicists in Medicine.)

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 11 C and 15 O, 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 11 C and 15 O 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 11 C (210 MeV u -1 ) and 15 O (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 15 O 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 11 C 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.

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, 11 C and 15 O 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 11 C and 15 O ions were concentrated in the regions which had high blood volume. The 11 C-labelled 11 CO 2 was detected in expired gas under the 11 C beam irradiation, while no significant signal was detected under the 15 O beam irradiation as a form of C 15 O 2 . Results suggested that the implanted 11 C 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.

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 11 C, 10 C and 15 O 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 12 C and 16 O beam measurements obtained with the BIC physics model.

In advanced ion therapy, the visualization of the range of incident ions in a patient's body is important for exploiting the advantages of this type of therapy. It is ideal to use radioactive ion beams for in-beam positron emission tomography (PET) imaging in particle therapy due to the high quality of PET images caused by the high signal-to-noise ratio. We have shown the feasibility of this idea through an in-beam PET study for 11 C and 15 O ion beams using the dedicated OpenPET system. In this work, we investigate the potential difference between the Bragg peak position and the position of the maximum detected positron-emitting fragments by a PET system for the radioactive beams of 11 C and 15 O. For this purpose, we measured the depth dose in a water phantom and performed PET scans of an irradiated PMMA phantom for the available beams of 11 C and 15 O at the Heavy Ion Medical Accelerator in Chiba (HIMAC). Then, we simulated the depth dose profiles in the water phantom and the yield of the positron-emitting fragments in a PMMA phantom for both available beams using the Monte Carlo code PHITS. The positions of the Bragg peak and maximum positron-emitting fragments from the measurements were well reproduced by simulation. The effect of beam energy broadening on the positional differences between two peaks was studied by simulating an irradiated PMMA phantom. The differences in position between the Bragg peak and the maximum positron-emitting fragments increased when the beam energy spread was broadened, although the differences were zero for the ideal mono-energetic beams. Greater differences were observed for 11 C ion beams compared to 15 O ion beams, although both beams had the same range in water, and the higher energy corresponded to a larger difference. For the known energy spread of the beams, the predicted differences between two peaks from the simulation were consistent with the measured data within submillimetre agreement.

Some recently developed brain-dedicated positron emission tomography (PET) scanners measure subjects in a sitting position. Sitting enables PET scanning under more natural conditions for the subjects and also helps with making the scanners smaller. It is unclear, however, how much the degree of head motion when sitting differs from the supine posture commonly employed in clinical PET. In this report, we describe development of a markerless and contactless head motion tracking system and a study of healthy volunteers in several different postures to determine the optimum posture for brain PET. We used Kinect ® (Microsoft) and developed software that can measure head motion with about 1 mm (translation) and less than 1° (rotation) accuracy. In the volunteer study, we measured the amount of head motion, with and without head fixation, in supine, normal sitting, and reclining postures. The results indicated that the normal sitting posture without head fixation had the largest head movement, and that the reclining and supine postures were similarly effective for minimizing head movement (average head movement of about 0.5 mm during 1 min). We also visualized the influence that head motion had on images for each pose by simulating the actual motions obtained from the volunteer study using a digital Hoffman phantom. Comparisons with the original image showed that the extent to which motion was reduced in the reclining and supine postures were quantitatively equivalent. The head motions of the volunteer studies were also reproduced using a mannequin head on a motorized stage to assess how well the proposed motion measurement system worked when used for motion correction. The results indicated that even though the system improved image quality for all postures, the reclining and supine postures could provide better image quality than the normal sitting posture.

Heavy ion therapy is a promising cancer therapy technique due to the sharper Bragg peak and smaller lateral scattering characteristics of heavy ion beams as compared to a proton therapy. Recently, the potential for radioactive ion beam therapy has been investigated in combination with the OpenPET system to improve the accuracy of in vivo beam range verification. However, the characteristics of the radioactive ion beams have not been investigated thoroughly. Optical imaging has been proposed as a novel high-resolution beam range estimation method for heavy ion beams. In this study, high-resolution luminescence imaging and Cerenkov light imaging were performed for the range estimation of radioactive ion beams such as 11 C and 15 O in the Heavy Ion Medical Accelerator in Chiba (HIMAC) secondary beam line. A polymethyl methacrylate (PMMA) phantom (10.0  ×  10.0  ×  9.9 cm 3 ) was irradiated by 11 C and 15 O ion beams. In order to obtain the in-beam luminescence and off-line beam Cerenkov light images, an optical system was used that consisted of a lens and a cooled CCD camera. The Bragg peaks and stopping positions of the 11 C and 15 O ion beams could be visualized by using the luminescence and Cerenkov light imaging, respectively. The Bragg peaks showed a good correlation with the peak of the luminescence profile with a positional discrepancy of 1 mm and 0.4 mm for the 11 C and 15 O ion beams, respectively. In conclusion, optical imaging using luminescence and Cerenkov light could be used for the precise range estimation of radioactive ion beams.

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.

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 ( 10 C, 11 C and 15 O) and two stable ion beams ( 12 C and 16 O) 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.

Depth of interaction (DOI) information is indispensable to improving the sensitivity and spatial resolution of positron emission tomography (PET) systems, especially for small field-of-view PET such as small animal PET and human brain PET. We have already developed a series of X'tal cube detectors for isotropic spatial resolution and we obtained the best isotropic resolution of 0.77 mm for detectors with six-sided readout. However, it is still challenging to apply the detector for PET systems due to the high cost of six-sided readout electronics and carrying out segmentation of a monolithic cubic scintillator in three dimensions using the subsurface laser engraving (SSLE) technique. In this work, we propose a more practical X'tal cube with a two-sided readout detector, which is made of crystal bars segmented in the height direction only by using the SSLE technique. We developed two types of prototype detectors with a 3 mm cubic segment and a 1.5 mm cubic segment by using 3  ×  3  ×  20 mm 3 and 1.5  ×  1.5  ×  20 mm 3 crystal bars segmented into 7 and 13 DOI segments, respectively, using the SSLE technique. First, the performance of the detector, composed of one crystal bar with different DOI segments and two thorough silicon via (TSV) multi-pixel photon counters (MPPCs) as readout at both ends of the crystal bar, were evaluated in order to demonstrate the capability of the segmented crystal bars as a DOI detector. Then, performance evaluation was carried out for a 4  ×  4 crystal array of 3  ×  3  ×  20 mm 3 with 7 DOI segments and an 8  ×  8 crystal array of 1.5  ×  1.5  ×  20 mm 3 with 13 DOI segments. Each readout included a 4  ×  4 channel of the 3  ×  3 mm 2 active area of the TSV MPPCs. The three-dimensional position maps of the detectors were obtained by the Anger-type calculation. All the segments in the 4  ×  4 array were identified very clearly when there was air between the crystal bars, as each crystal bar was coupled to one channel of the MPPCs; however, it was necessary to optimize optical conditions between crystal bars for the 8  ×  8 array because of light sharing between crystal bars coupled to one channel of the MPPCs. The optimization was performed for the 8  ×  8 array by inserting reflectors fully or partially between the crystal bars and the best crystal identification performance was obtained with the partial reflectors between the crystal bars. The mean energy resolutions at the 511 keV photo peak for the 4  ×  4 array with air between the crystal bars and for the 8  ×  8 array with partial reflectors between the crystal bars were 10.1%  ±  0.3% and 10.8%  ±  0.8%, respectively. Timing resolutions of 783  ±  36 ps and 1.14  ±  0.22 ns were obtained for the detectors composed of the 4  ×  4 array and the 8  ×  8 array with partial reflectors, respectively. These values correspond to single photon timing resolutions. Practical X'tal cubes with 3 mm and 1.5 mm DOI resolutions and two-sided readout were developed.

Nuclear medicine imaging is an important tool for cancer diagnosis, brain research, molecular imaging research and so on. Therefore, various imaging techniques and methods are being developed and investigated in nuclear medicine physics. In this report, we introduce state-of-the-art techniques, such as Compton camera imaging, time-of-flight positron emission tomography, semiconductor detectors for medical applications, image reconstruction and deep learning, which were reported in the 2017 IEEE Nuclear Science Symposium & Medical Imaging Conference.

We have been working on the development of a PET insert for existing magnetic resonance imaging (MRI) systems for simultaneous PET/MR imaging, which integrates radiofrequency (RF)-shielded PET detector modules with an RF head coil. In order to avoid interferences between the PET detector circuits and the different MRI-generated electromagnetic fields, PET detector circuits were installed inside eight Cu-shielded fiber-reinforced plastic boxes, and these eight shielded PET modules were integrated in between the eight elements of a 270-mm-diameter and 280-mm-axial-length cylindrical birdcage RF coil, which was designed to be used with a 3-T clinical MRI system. The diameter of the PET scintillators with a 12-mm axial field-of-view became 255mm, which was very close to the imaging region. In this study, we have investigated the effects of this PET/RF-coil integrated system on the performance of MRI, which include the evaluation of static field (B o ) inhomogeneity, RF field (B 1 ) distribution, local specific absorption rate (SAR) distribution, average SAR, and signal-to-noise ratio (SNR). For the central 170-mm-diameter and 80-mm-axial-length of a homogenous cylindrical phantom (with the total diameter of 200mm and axial-length of 100mm), an increase of about a maximum of 3μT in the B o inhomogeneity was found, both in the central and 40-mm off-centered transverse planes, and a 5 percentage point increase of B 1 field inhomogeneity was observed in the central transverse plane (from 84% without PET to 79% with PET), while B 1 homogeneity along the coronal plane was almost unchanged (77%) following the integration of PET with the RF head coil. The average SAR and maximum local SAR were increased by 1.21 and 1.62 times, respectively. However, the SNR study for both spin-echo and gradient-echo sequences showed a reduction of about 70% and 60%, respectively, because of the shielded PET modules. The overall results prove the feasibility of this integrated PET/RF-coil system for using with the existing MRI system., (Copyright © 2017 Elsevier Inc. All rights reserved.)

There is a growing interest in developing brain PET scanners with high sensitivity and high spatial resolution for early diagnosis of neurodegenerative diseases and studies of brain functions. Sensitivity of the PET scanner can be improved by increasing the solid angle. However, conventional PET scanners are designed based on a cylindrical geometry, which may not be the most efficient design for brain imaging in terms of the balance between sensitivity and cost. We proposed a dedicated brain PET scanner based on a hemispheric shape detector and a chin detector (referred to as the helmet-chin PET), which is designed to maximize the solid angle by increasing the number of lines-of-response in the hemisphere. The parallax error, which PET scanners with a large solid angle tend to have, can be suppressed by the use of depth-of-interaction detectors. In this study, we carry out a realistic evaluation of the helmet-chin PET using Monte Carlo simulation based on the 4-layer GSO detector which consists of a 16  ×  16  ×  4 array of crystals with dimensions of 2.8  ×  2.8  ×  7.5 mm 3 . The purpose of this simulation is to show the gain in imaging performance of the helmet-chin PET compared with the cylindrical PET using the same number of detectors in each configuration. The sensitivity of the helmet-chin PET evaluated with a cylindrical phantom has a significant increase, especially at the top of the (field-of-view) FOV. The peak-NECR of the helmet-chin PET is 1.4 times higher compared to the cylindrical PET. The helmet-chin PET provides relatively low noise images throughout the FOV compared to the cylindrical PET which exhibits enhanced noise at the peripheral regions. The results show the helmet-chin PET can significantly improve the sensitivity and reduce the noise in the reconstructed images.

The accumulation of induced radioactivity within in-beam PET scanner scintillators is of concern for its long-term clinical usage in particle therapy. To estimate the effects on OpenPET which we are developing for in-beam PET based on GSOZ (Zi doped Gd2SiO5), we measured the induced radioactivity of GSO activated by secondary fragments in a water phantom irradiation by a (12)C beam with an energy of 290 MeV u(-1). Radioisotopes of Na, Ce, Eu, Gd, Nd, Pm and Tb including positron emitters were observed in the gamma ray spectra of the activated GSO with a high purity Ge detector and their absolute radioactivities were calculated. We used the Monte Carlo simulation platform, Geant4 in which the observed radioactivity was assigned to the scintillators of a precisely reproduced OpenPET and the single and coincidence rates immediately after one treatment and after one-year usage were estimated for the most severe conditions. Comparing the highest coincidence rate originating from the activated scintillators (background) and the expected coincidence rate from an imaging object (signal), we determined the expected signal-to-noise ratio to be more than 7 within 3 min and more than 10 within 1 min from the scan start time. We concluded the effects of scintillator activation and their accumulation on the OpenPET imaging were small and clinical long-term usage of the OpenPET was feasible.

Multi-pixel photon counters (MPPCs) have been used instead of photomultiplier tubes for positron emission tomography combined with magnetic resonance (PET-MR). However, the effects of the magnetic field (MF) on the intrinsic properties-gain, cross-talk, after-pulsing, and dark-count-have not been sufficiently investigated. Therefore, we measured these properties for two types of MPPCs-S10931-50P and S12572-50P-in a static 7-T MF. These properties were measured with a pulse-shape analysis using pulse data acquired by a digital oscilloscope in the presence of the MF (w/MF) and the absence of the MF (w/o MF) by changing the supplied over-voltages (from 0.95 to 2.1 V for S10931 and from 2.1 to 3.3 V for S12572). No significant differences between the w/MF and w/o MF cases were observed for either MPPC, suggesting that the gain, cross-talk, after-pulsing, and dark-count are insensitive to a 7-T MF. The present work shows that constant MPPC performance is expected under a strong MF and demonstrates positive results for PET-MR.

In dose verification techniques of particle therapies based on in-beam positron emission tomography (PET), the causes of washout of positron emitters by physiological effects should be clarified to correct washout for accurate verification. As well, the quantitative washout rate has a potential usefulness as a diagnostic index which should be explored. Therefore, we measured washout rates of rat brain after vasodilator acetazolamide loading to investigate the possible effects of blood flow on washout. Six rat brains were irradiated by a radioisotope (11)C beam and time activity curves on the whole brains were obtained with a small single-ring OpenPET prototype. Then, washout rates were calculated with the Mizuno model, where two washout rates (k 2m and k 2s ) were assumed, and a two-compartment model including efflux from tissue to blood (k 2) and influx (k 3) and efflux (k 4) between the two tissue compartments. Before the irradiations, we used laser-Doppler flowmetry to confirm that acetazolamide increased cerebral blood flow (CBF) of a rat. We compared means of k 2m , k 2s and k 2, k 3 and k 4 without acetazolamide loading (Rest) and with acetazolamide loading (ACZ). For all k values, ACZ values were lower than Rest values. In other words, though CBF increased, washout rates were decreased. This may be attributed to the implanted (11)C reacting to form (11)CO2. Because acetazolamide increased the concentration of CO2 in brain, suppressed diffusion of (11)CO2 and decomposition of (11)CO2 into ions were prevented.

The single-ring OpenPET (SROP), for which the detector arrangement has a cylinder shape cut by two parallel planes at a slant angle to form an open space, is our original proposal for in-beam PET. In this study, we developed a small prototype of an axial-shift type SROP (AS-SROP) with a novel transformable architecture for a proof-of-concept. In the AS-SROP, detectors originally forming a cylindrical PET are axially shifted little by little. We designed the small AS-SROP prototype for 4-layer depth-of-interaction detectors arranged in a ring diameter of 250 mm. The prototype had two modes: open and closed. The open mode formed the SROP with the open space of 139 mm and the closed mode formed a conventional cylindrical PET. The detectors were simultaneously moved by a rotation handle allowing them to be transformed between the two modes. We evaluated the basic performance of the developed prototype and carried out in-beam imaging tests in the HIMAC using (11)C radioactive beam irradiation. As a result, we found the open mode enabled in-beam PET imaging at a slight cost of imaging performance; the spatial resolution and sensitivity were 2.6 mm and 5.1% for the open mode and 2.1 mm and 7.3% for the closed mode. We concluded that the AS-SROP can minimize the decrease of resolution and sensitivity, for example, by transforming into the closed mode immediately after the irradiation while maintaining the open space only for the in-beam PET measurement.

We previously have developed the photoresponsive tetra-gel and nanoparticles for controlling the function of the encapsulated substance by UV irradiation. However, the penetration ability of the UV is not high enough. Here, we developed a radiation-responsive tetra-gel and nanoparticle based on γ-ray-responsive X-shaped polyethylene glycol (PEG) linker with a disulfide bond. The nanoparticle could retain small molecules and biomacromolecules. γ-Rays were used as a trigger signal because of their higher penetrating ability. This allowed a spatiotemporal release and control of the encapsulated substances from the nanoparticle in the deeper region, which is impossible by using light exposure (ultraviolet, visible, and near-infrared).

Recently, various types of PET-MRI systems have been developed by a number of research groups. However, almost all of the PET detectors used in these PET-MRI systems have no depth-of-interaction (DOI) capability. The DOI detector can reduce the parallax error and lead to improvement of the performance. We are developing a new PET-MRI system which consists of four-layer DOI detectors positioned close to the measured object to achieve high spatial resolution and high scanner sensitivity. As a first step, we are investigating influences the PET detector and the MRI system have on each other using a prototype four-layer DOI-PET detector. This prototype detector consists of a lutetium yttrium orthosilicate crystal block and a 4 × 4 multi-pixel photon counter array. The size of each crystal element is 1.45 mm × 1.45 mm × 4.5 mm, and the crystals are arranged in 6 × 6 elements × 4 layers with reflectors. The detector and some electric components are packaged in an aluminum shielding box. Experiments were carried out with 3.0 T MRI (GE, Signa HDx) and a birdcage-type RF coil. We demonstrated that the DOI-PET detector was normally operated in simultaneous measurements with no influence of the MRI measurement. A slight influence of the PET detector on the static magnetic field of the MRI was observed near the PET detector. The signal-to-noise ratio was decreased by presence of the PET detector due to environmental noise entering the MRI room through the cables, even though the PET detector was not powered up. On the other hand, no influence of electric noise from the PET detector in the simultaneous measurement on the MRI images was observed, even though the PET detector was positioned near the RF coil.

Positron annihilation spectroscopy (PAS) spectra of biological tissue in 11C irradiation are reported and spatial resolution coefficient of positron emission tomography (PET) obtained from the PAS spectrum is discussed for 11C irradiation. A PAS spectrum of the biological tissue with water is the same as that of the water pool phantom in 11C irradiation. However, a PAS spectrum of the biological tissue with less water differs from that of the water pool phantom. The PET spatial resolution coefficient depends on the kind of biological tissue. However, the PET spatial resolution coefficient, 0.00243±0.00014, can be used as a common value of maximum limit.

In the development of depth-of-interaction (DOI)-positron emission tomography (PET) detectors, one of the important steps toward their practical use is an evaluation of their imaging performance, such as the spatial resolution as measured by use of a point source and a one-pair experimental system which simulates actual PET geometries. The DOI-PET detectors have a broad field of view providing good imaging performance compared with conventional detectors. Therefore, evaluation including the region from the center to the periphery close to the detector ring is required in an effort to show their advanced performance regarding uniform spatial resolution. In this study, we aimed to develop and evaluate an efficient one-pair experimental system for demonstration of the DOI-PET detector performance. For this purpose, we propose a one-pair experimental system that can simulate an arbitrary ring diameter and acquire projection data efficiently by skipping unnecessary combinations according to the position of the point source. As a result, the proposed system and our measuring scheme could significantly reduce the total measurement time, especially for a large ring size such as that used in brain PET scanners and whole-body PET scanners. We used the system to evaluate the X'tal cube PET detector with a 2-mm cubic crystal array arranged in simulated PET geometries with ring diameters of 8.2 and 14.6 cm for 12 and 18 detector blocks, respectively. The results showed that a uniform spatial resolution was achieved even in the peripheral region, and measurements were obtained semi-automatically in a short time.

For clinical studies, the effects of the intrinsic radioactivity of lutetium-based scintillators such as LSO used in PET imaging can be ignored within a narrow energy window. However, the intrinsic radioactivity becomes problematic when used in low-count-rate situations such as gene expression imaging or in-beam PET imaging. Time-of-flight (TOF) measurement capability promises not only to improve PET image quality, but also to reduce intrinsic random coincidences. On the other hand, we have developed a new reduction method for intrinsic random coincidence events based on multiple-coincidence information. Without the energy window, an intrinsic random coincidence is detected simultaneously with an intrinsic true coincidence as a multiple coincidence. The multiple-coincidence events can serve as a guide to identification of the intrinsic coincidences. After rejection of multiple-coincidence events detected with a wide energy window, data obtained included a few intrinsic random and many intrinsic true coincidence events. We analyzed the effect of intrinsic radioactivity and used Monte Carlo simulation to test both the TOF-based method and the developed multiple-coincidence-based (MC-based) method for a whole-body LSO-PET scanner. Using the TOF- and MC-based reduction methods separately, we could reduce the intrinsic random coincidence rates by 77 and 30 %, respectively. Also, the intrinsic random coincidence rate could be reduced by 84 % when the TOF+MC reduction methods were applied. The developed MC-based method showed reduced number of the intrinsic random coincidence events, but the reduction performance was limited compared to that of the TOF-based reduction method.

In-beam positron emission tomography (PET) can enable visualization of an irradiated field using positron emitters (β+ decay). In particle therapies, many kinds of secondary particles are produced by nuclear interactions, which affect PET imaging. Our purpose in this work was to evaluate effects of secondary particles on in-beam PET imaging using the Monte Carlo simulation code, Geant4, by reproducing an experiment with a small OpenPET prototype in which a PMMA phantom was irradiated by a (11)C beam. The number of incident particles to the detectors and their spectra, background coincidence for the PET scan, and reconstructed images were evaluated for three periods, spill-time (beam irradiation), pause-time (accelerating the particles) and beam-off time (duration after the final spill). For spill-time, we tested a background reduction technique in which coincidence events correlated with the accelerator radiofrequency were discarded (RF gated) that has been proposed in the literature. Also, background generation processes were identified. For spill-time, most background coincidences were caused by prompt gamma rays, and only 1.4% of the total coincidences generated β+ signals. Differently, for pause-time and beam-off time, more than 75% of the total coincidence events were signals. Using these coincidence events, we failed to reconstruct images during the spill-time, but we obtained successful reconstructions for the pause-time and beam-off time, which was consistent with the experimental results. From the simulation, we found that the absence of materials in the beam line and using the RF gated technique improved the signal-to-noise ratio for the spill-time. From an additional simulation with range shifter-less irradiation and the RF gated technique, we showed the feasibility of image reconstruction during the spill-time.

Our purpose in this work was to evaluate the performance of a 4-layer depth-of-interaction (DOI) detector composed of GSO crystals by use of a position-sensitive photomultiplier tube (PMT) with a super-bialkali photocathode (SBA) by comparing it with a standard bialkali photocathode (BA) regarding the ability to identify the scintillating crystals, energy resolution, and timing resolution. The 4-layer DOI detector was composed of a 16 × 16 array of 2.9 × 2.9 × 7.5 mm(3) GSO crystals for each layer and an 8 × 8 multi-anode array type position-sensitive PMT. The DOI was achieved by a reflector control method, and the Anger method was used for calculating interacting points. The energy resolution in full width at half-maximum (FWHM) at 511 keV energy for the top layer (the farthest from the PMT) was improved and was 12.0% for the SBA compared with the energy resolution of 12.7% for the BA. As indicators of crystal identification ability, the peak-to-valley ratio and distance-to-width ratio were calculated; the latter was defined as the average of the distance between peaks per the average of the peak width. For both metrics, improvement of several percent was obtained; for example, the peak-to-valley ratio was increased from 1.78 (BA) to 1.86 (SBA), and the distance-to-width ratio was increased from 1.47 (BA) to 1.57 (SBA). The timing resolution (FWHM) in the bottom layer was improved slightly and was 2.4 ns (SBA) compared with 2.5 ns (BA). Better performance of the DOI detector is expected by use of a super bialkali photocathode.

The X'tal cube is a next-generation DOI detector for PET that we are developing to offer higher resolution and higher sensitivity than is available with present detectors. It is constructed from a cubic monolithic scintillation crystal and silicon photomultipliers which are coupled on various positions of the six surfaces of the cube. A laser-processing technique is applied to produce 3D optical boundaries composed of micro-cracks inside the monolithic scintillator crystal. The current configuration is based on an empirical trial of a laser-processed boundary. There is room to improve the spatial resolution by optimizing the setting of the laser-processed boundary. In fact, the laser-processing technique has high freedom in setting the parameters of the boundary such as size, pitch, and angle. Computer simulation can effectively optimize such parameters. In this study, to design optical characteristics properly for the laser-processed crystal, we developed a Monte Carlo simulator which can model arbitrary arrangements of laser-processed optical boundaries (LPBs). The optical characteristics of the LPBs were measured by use of a setup with a laser and a photo-diode, and then modeled in the simulator. The accuracy of the simulator was confirmed by comparison of position histograms obtained from the simulation and from experiments with a prototype detector composed of a cubic LYSO monolithic crystal with 6 × 6 × 6 segments and multi-pixel photon counters. Furthermore, the simulator was accelerated by parallel computing with general-purpose computing on a graphics processing unit. The calculation speed was about 400 times faster than that with a CPU.

We are developing a novel PET detector with 3D isotropic resolution called a crystal (X'tal) cube. The X'tal cube detector consists of a crystal block all 6 surfaces of which are covered with silicon photomultipliers (SiPMs). We have developed a prototype detector with 3D isotropic 1 mm resolution. On the other hand, when the X'tal cubes are arranged to form a PET scanner, insensitive inter-detector gaps made by the SiPM arrays should not be too wide, or, better yet, they should be removed. Reduction of the number of SiPMs will also be reflected in the production costs. Therefore, reducing the number of faces to be connected to the SiPMs has become our top priority. In this study, we evaluated the effect of reducing the number of SiPMs on the positioning accuracy through numerical simulations. Simulations were performed with the X'tal cube, which was composed of a 6 × 6 × 6 array of Lu2x Gd2(1-x)SiO5:Ce crystal elements with dimensions of (3.0 mm)(3). Each surface of the crystal block was covered with a 4 × 4 array of SiPMs, each of which had a (3.0 mm)(2) active area. For material between crystal elements, we compared two: optical glue and an air gap. The air gap showed a better crystal identification performance than did the optical glue, although a good crystal identification performance was obtained even with optical glue for the 6-face photodetection. In conclusion, the number of photodetection faces could be reduced to two when the gap material was air.

We are developing a three-dimensional (3D) position-sensitive detector with isotropic spatial resolution, the X'tal cube. Originally, our design consisted of a crystal block for which all six surfaces were covered with arrays of multi-pixel photon counters (MPPCs). In this paper, we examined the feasibility of reducing the number of surfaces on which a MPPC array must be connected with the aim of reducing the complexity of the system. We evaluated two kinds of laser-processed X'tal cubes of 3 mm and 2 mm pitch segments while varying the numbers of the 4 × 4 MPPC arrays down to two surfaces. The sub-surface laser engraving technique was used to fabricate 3D grids into a monolithic crystal block. The 3D flood histograms were obtained by the Anger-type calculation. Two figures of merit, peak-to-valley ratios and distance-to-width ratios, were used to evaluate crystal identification performance. Clear separation was obtained even in the 2-surface configuration for the 3 mm X'tal cube, and the average peak-to-valley ratios and the distance-to-width ratios were 6.7 and 2.6, respectively. Meanwhile, in the 2 mm X'tal cube, the 6-surface configuration could separate all crystals and even the 2-surface case could also, but the flood histograms were relatively shrunk in the 2-surface case, especially on planes parallel to the sensitive surfaces. However, the minimum peak-to-valley ratio did not fall below 3.9. We concluded that reducing the numbers of MPPC readout surfaces was feasible for both the 3 mm and the 2 mm X'tal cubes.

The X'tal cube is a depth-of-interaction (DOI)-PET detector which is aimed at obtaining isotropic resolution by effective readout of scintillation photons from the six sides of a crystal block. The X'tal cube is composed of the 3D crystal block with isotropic resolution and arrays of multi-pixel photon counters (MPPCs). In this study, to fabricate the 3D crystal block efficiently and precisely, we applied a sub-surface laser engraving (SSLE) technique to a monolithic crystal block instead of gluing segmented small crystals. The SSLE technique provided micro-crack walls which carve a groove into a monolithic scintillator block. Using the fabricated X'tal cube, we evaluated its intrinsic spatial resolution to show a proof of concept of isotropic resolution. The 3D grids of 2 mm pitch were fabricated into an 18 × 18 × 18 mm(3) monolithic lutetium yttrium orthosilicate (LYSO) crystal by the SSLE technique. 4 × 4 MPPCs were optically coupled to each surface of the crystal block. The X'tal cube was uniformly irradiated by (22)Na gamma rays, and all of the 3D grids on the 3D position histogram were separated clearly by an Anger-type calculation from the 96-channel MPPC signals. Response functions of the X'tal cube were measured by scanning with a (22)Na point source. The gamma-ray beam with a 1.0 mm slit was scanned in 0.25 mm steps by positioning of the X'tal cube at vertical and 45° incident angles. The average FWHM resolution at both incident angles was 2.1 mm. Therefore, we confirmed the isotropic spatial resolution performance of the X'tal cube.

We have proposed an OpenPET geometry which consists of two axially separated detector rings. The open gap is suitable for in-beam PET. We have developed the small prototype of the OpenPET especially for a proof of concept of in-beam imaging. This paper presents an overview of the main features implemented in this prototype. We also evaluated the detector performance. This prototype was designed with 2 detector rings having 8 depth-of-interaction detectors. Each detector consisted of 784 Lu(2x)Gd(2(1-x))SiO₅:Ce (LGSO) which were arranged in a 4-layer design, coupled to a position-sensitive photomultiplier tube (PS-PMT). The size of the LGSO array was smaller than the sensitive area of the PS-PMT, so that we could obtain sufficient LGSO identification. Peripheral LGSOs near the open gap directly detect the gamma rays on the side face in the OpenPET geometry. Output signals of two detectors stacked axially were projected onto one 2-dimensional position histogram for reduction of the scale of a coincidence processor. Front-end circuits were separated from the detector head by 1.2-m coaxial cables for the protection of electronic circuits from radiation damage. The detectors had sufficient crystal identification capability. Cross talk between the combined two detectors could be ignored. The timing and energy resolutions were 3.0 ns and 14%, respectively. The coincidence window was set 20 ns, because the timing histogram showed that not only the main peak, but also two small shifted peaks were caused by the coaxial cable. However, the detector offers the promise of sufficient performance, because random coincidences are at a nearly undetectable level for in-beam PET experiments.

We are developing a novel, general purpose isotropic-3D PET detector X'tal cube which has high spatial resolution in all three dimensions. The research challenge for this detector is implementing effective detection of scintillation photons by covering six faces of a segmented crystal block with silicon photomultipliers (SiPMs). In this paper, we developed the second prototype of the X'tal cube for a proof-of-concept. We aimed at realizing an ultimate detector with 1.0 mm(3) cubic crystals, in contrast to our previous development using 3.0 mm(3) cubic crystals. The crystal block was composed of a 16 × 16 × 16 array of lutetium gadolinium oxyorthosilicate (LGSO) crystals 0.993 × 0.993 × 0.993 mm(3) in size. The crystals were optically glued together without inserting any reflector inside and 96 multi-pixel photon counters (MPPCs, S10931-50P, i.e. six faces each with a 4 × 4 array of MPPCs), each having a sensitive area of 3.0 × 3.0 mm(2), were optically coupled to the surfaces of the crystal block. Almost all 4096 crystals were identified through Anger-type calculation due to the finely adjusted reflector sheets inserted between the crystal block and light guides. The reflector sheets, which formed a belt of 0.5 mm width, were placed to cover half of the crystals of the second rows from the edges in order to improve identification performance of the crystals near the edges. Energy resolution of 12.7% was obtained at 511 keV with almost uniform light output for all crystal segments thanks to the effective detection of the scintillation photons.

Conventionally, block detectors, which consist of a two-dimensionally segmented scintillator array with inserted reflectors, are often used for PET. On the other hand, PET detectors with a monolithic block have been investigated because they are expected to offer higher resolution than do segmented crystal arrays. However, previous reports focused on detectors dedicated as small-animal PET, and the thickness was not good enough to stop 511-keV radiation. We developed a PET detector that uses a large and thick monolithic LYSO and 64-channel PS-PMT. When the LYSO was covered with reflectors, the spatial resolution, which was 3 mm FWHM at the center, rapidly became worse at the edge. We eliminated the loss of spatial resolution by replacing the reflectors with black paper, but the light output was decreased. Therefore, we concluded that spatial resolution and light output were in a trade-off relationship due to the edge effect of scintillation light.

The OpenPET geometry is our new idea to visualize a physically opened space between two detector rings. In this paper, we developed the first small prototype to show a proof-of-concept of OpenPET imaging. Two detector rings of 110 mm diameter and 42 mm axial length were placed with a gap of 42 mm. The basic imaging performance was confirmed through phantom studies; the open imaging was realized at the cost of slight loss of axial resolution and 24% loss of sensitivity. For a proof-of-concept of PET image-guided radiation therapy, we carried out the in-beam tests with (11)C radioactive beam irradiation in the heavy ion medical accelerator in Chiba to visualize in situ distribution of primary particles stopped in a phantom. We showed that PET images corresponding to dose distribution were obtained. For an initial proof-of-concept of real-time multimodal imaging, we measured a tumor-inoculated mouse with (18)F-FDG, and an optical image of the mouse body surface was taken during the PET measurement by inserting a digital camera in the ring gap. We confirmed that the tumor in the gap was clearly visualized. The result also showed the extension effect of an axial field-of-view (FOV); a large axial FOV of 126 mm was obtained with the detectors that originally covered only an 84 mm axial FOV. In conclusion, our initial imaging studies showed promising performance of the OpenPET.

Crystals of the title compound, {(C(6)H(5)C(2)H(4)NH(3))(2)[PbBr(4)]}(n), were grown at room temperature from a solution in N,N-dimethyl-formamide (DMF) using nitro-methane as the poor solvent. This perovskite-type organic-inorganic hybrid compound consists of well ordered sheets of corner-sharing disordered PbBr(6) octa-hedra separated by bilayers of phenethyl-ammonium cations. The octa-hedra are rotated and tilted due to N-H⋯Br hydrogen bonds with the ammonium groups, generating a superstructure in the unit cell similar to that of the tetra-chloridoplumbate (C(6)H(5)C(2)H(4)NH(3))(2)[PbCl(4)].

We have proposed an 'OpenPET' geometry which consists of two detector rings of axial length W each axially separated by a gap G. In order to obtain an axially continuous field-of-view (FOV) of 2W+G, the maximum limit for G must be W. However, two valleys of sensitivity appear, one on each side of the gap. In practice, the gap should be G

Objective: One trend in positron emission tomography (PET) instrumentation over the last decade has been the development of scanners dedicated to small animals such as rats and mice. Thicker crystals, which are necessary to obtain higher sensitivity, result in degraded spatial resolution in the peripheral field-of-view (FOV) owing to the parallax error. On the other hand, we are developing the jPET-D4, which is a dedicated human brain PET scanner that has a capability for depth-of-interaction (DOI) measurement. Although its crystal width is about twice that of commercially available small animal PET scanners, we expect the jPET-D4 to have a potential for small animal imaging by making full use of the DOI information. In this article, we investigate the jPET-D4's potential for small animal imaging by comparing it with the microPET Focus220, a state-of-the-art PET scanner dedicated to small animals., Methods: The jPET-D4 uses four-layered GSO crystals measuring 2.9 mm x 2.9 mm x 7.5 mm, whereas the microPET Focus220 uses a single layer of LSO crystals measuring 1.5 mm x 1.5 mm x 10.0 mm. First, the absolute sensitivity, counting rate performance and spatial resolution of both scanners were measured. Next a small hot-rod phantom was used to compare their imaging performance. Finally, a rat model with breast tumors was imaged using the jPET-D4., Results: Thanks to the thicker crystals and the longer axial FOV, the jPET-D4 had more than four times higher sensitivity than the microPET Focus220. The noise equivalent counting-rate performance of the jPETD4 reached 1,024 kcps for a rat-size phantom, whereas that of the microPET Focus220 reached only 165 kcps. At the center of the FOV, the resolution was 1.7 mm for the microPET Focus220, whereas it was 3.2 mm for the jPET-D4. On the other hand, the difference of resolution became smaller at the off-center position because the radial resolution degraded faster for the microPET Focus220. The results of phantom imaging showed that the jPET-D4 was comparable to the microPET Focus220 at the off-center position even as the microPET Focus220 outperformed the jPET-D4 except for the peripheral FOV., Conclusions: The jPET-D4 human brain PET scanner, which was designed to achieve not only high resolution but also high sensitivity by measuring DOI information, was proven to have a potential for small animal imaging.

We have proposed a new "OpenPET" geometry consisting of two detector rings of axial length W each separated by a gap G. For obtaining an axially continuous field of view (FOV) of 2W + G, the maximum limit for G must be W. However, two valleys of sensitivity appear on both sides of the gap. Setting a more limited range for the gap as G < W, which is desirable for filling in the sensitivity valleys, results in not only a shortened gap, but also a shortened axial FOV. In this paper, we propose an alternative method for improving the uniformity of sensitivity by shifting two detector rings axially closer or further apart at the same velocity to each other. In addition, image reconstruction of the OpenPET is an incomplete problem, and low-frequency components are missing in the gap. Therefore, the proposed method is also expected to improve the conditions for the inverse problem. We simulated an OpenPET scanner which measures events simultaneously by shifting the detector rings. The results showed that the right and left peaks of the sensitivity approach each other upon shifting of the detector rings, and these valleys of sensitivity are effectively recovered. The results also showed that distortion, which is observed for objects containing low-frequency components, is reduced. Larger detector shifts allow a more uniform axial distribution of sensitivity and a higher image quality, but at the cost of a smaller minimum gap. Therefore, an appropriate detector-shifting pattern should be determined based on the desired scanner application.

The long patient port of a PET scanner tends to put stress on patients, especially patients with claustrophobia. It also prevents doctors and technicians from taking care of patients during scanning. In this paper, we proposed an 'open PET' geometry, which consists of two axially separated detector rings. A long and continuous field-of-view (FOV) including a 360 degrees opened gap between two detector rings can be imaged enabling a fully 3D image reconstruction of all the possible lines-of-response. The open PET will become practical if iterative image reconstruction methods are applied even though image reconstruction of the open PET is analytically an incomplete problem. First we implemented a 'masked' 3D ordered subset expectation maximization (OS-EM) in which the system matrix was obtained from a long 'gapless' scanner by applying a mask to detectors corresponding to the open space. Next, in order to evaluate imaging performance of the proposed open PET geometry, we simulated a dual HR+ scanner (ring diameter of D = 827 mm, axial length of W = 154 mm x 2) separated by a variable gap. The gap W was the maximum limit to have axially continuous FOV of 3W though the maximum diameter of FOV at the central slice was limited to D/2. Artifacts, observed on both sides of the open space when the gap exceeded W, were effectively reduced by inserting detectors partially into unnecessary open spaces. We also tested the open PET geometry using experimental data obtained by the jPET-D4. The jPET-D4 is a prototype brain scanner, which has 5 rings of 24 detector blocks. We simulated the open jPET-D4 with a gap of 66 mm by eliminating 1 block-ring from experimental data. Although some artifacts were seen at both ends of the opened gap, very similar images were obtained with and without the gap. The proposed open PET geometry is expected to lead to realization of in-beam PET, which is a method for an in situ monitoring of charged particle therapy, by letting the beams pass through the gap. The proposed open PET geometry will also allow simultaneous PET/CT measurements of the same PET FOV as the CT FOV, in contrast to the conventional PET/CT where each FOV is separated by several tens of centimeters.

The jPET-D4 is a brain positron emission tomography (PET) scanner that we have developed to meet user demands for high sensitivity and high spatial resolution. For this scanner, we developed a four-layer depth-of-interaction (DOI) detector. The four-layer DOI detector is a key component for the jPET-D4, its performance has great influence on the overall system performance. Previously, we reported the original technique for encoding four-layer DOI. Here, we introduce the final design of the jPET-D4 detector and present the results of an investigation on uniformity in performance of the detector. The performance evaluation was done over the 120 DOI crystal blocks for the detectors, which are to be assembled into the jPET-D4 scanner. We also introduce the crystal assembly method, which is simple enough, even though each DOI crystal block is composed of 1,024 crystal elements. The jPET-D4 detector consists of four layers of 16 x 16 Gd(2)SiO(5) (GSO) crystals and a 256-channel flat-panel position-sensitive photomultiplier tube (256ch FP-PMT). To identify scintillated crystals in the four-layer DOI detector, we use pulse shape discrimination and position discrimination on the two-dimensional (2D) position histogram. For pulse shape discrimination, two kinds of GSO crystals that show different scintillation decay time constants are used in the upper two and lower two layers, respectively. Proper reflector arrangement in the crystal block then allows the scintillated crystals to be identified in these two-layer groupings with two 2D position histograms. We produced the 120 DOI crystal blocks for the jPET-D4 system, and measured their characteristics such as the accuracy of pulse shape discrimination, energy resolution, and the pulse height of the full energy peak. The results show a satisfactory and uniform performance of the four-layer DOI crystal blocks; for example, misidentification rate in each GSO layer is <5% based on pulse shape discrimination, the averaged energy resolutions for the central four crystals of the first (farthest from the FP-PMT), second, third, and 4th layers are 15.7 +/- 1.0, 15.8 +/- 0.6, 17.7 +/- 1.2, and 17.3 +/- 1.4%, respectively, and variation in pulse height of the full energy peak among the four layers is <5% on average.

Annihilation photon acollinearity is a fundamental but little investigated problem in positron emission tomography (PET). In this paper, the cause of the angular deviation from 180.00 degrees is described as well as how to evaluate it under conditions of a spatially distributed radiation source and a limited acquisition time for the human body. A relationship between the shape of the photopeak spectrum and the angular distribution is formulated using conservation laws of momentum and energy over the pair annihilation. Then the formula is used to evaluate the acollinearity for a pool phantom and the human body with FDG injected. The angular distribution for the pool phantom agrees well with that for pure water which had been directly measured by Colombino et al in 1965 (Nuovo Cimento 38 707-23), and also with that for the human body determined in this study. Pure water can be considered as a good approximation of the human body regarding the angular deviation. The blurring coefficient to be multiplied by the ring diameter in calculations of the PET spatial resolution is experimentally determined for the first time as 0.00243 +/- 0.00014; this is 10% larger than the value widely used by investigators.

We introduce experimental systems which use accelerators to evaluate scintillation properties such as scintillation intensity, wavelength, and lifetime. A single crystal of good optical quality is often unavailable during early stages in the research and development (R&D) of new scintillator materials. Because of their beams' high excitation power and/or low penetration depth, accelerators facilitate estimation of the properties of early samples which may only be available as powders, thin films, and very small crystals. We constructed a scintillation spectrum measurement system that uses a Van de Graaff accelerator and an optical multichannel analyzer to estimate the relative scintillation intensity. In addition, we constructed a scintillation time profile measurement system that uses an electron linear accelerator and a femtosecond streak camera or a microchannel plate photomultiplier tube followed by a digital oscilloscope to determine the scintillation lifetimes. The time resolution is approximately 10 ps. The scintillation spectra or time profiles can be obtained in a significantly shorter acquisition time in comparison with that required by conventional measuring systems. The advantages of the systems described in this study can significantly promote the R&D of novel scintillator materials.

The jPET-D4 is the first PET scanner to introduce a unique four-layer depth-of-interaction (DOI) detector scheme in order to achieve high sensitivity and uniform high spatial resolution. This paper compares measurement and Monte Carlo simulation results of the static physics performance of this prototype research PET scanner. Measurement results include single and coincidence energy spectra, point and line source sensitivities, axial sensitivity profile (slice profile) and scatter fraction. We use GATE (Geant4 application for tomographic emission) as a Monte Carlo radiation transport model. Experimental results are reproduced well by the simulation model with reasonable assumptions on characteristic responses of the DOI detectors. In a previous study, the jPET-D4 was shown to provide a uniform spatial resolution as good as 3 mm (FHWM). In the present study, we demonstrate that a high sensitivity, 11.3 +/- 0.5%, is provided at the FOV centre. However, about three-fourths of this sensitivity is related to multiple-crystal events, for which some misidentification of the crystal cannot be avoided. Therefore, it is crucial to develop a more efficient way to identify the crystal of interaction and to reduce misidentification in order to make use of these high performance values simultaneously. We expect that effective sensitivity can be improved by replacing the GSO crystals with more absorptive crystals such as BGO and LSO. The results we describe here are essential to take full advantage of the next generation PET systems that have DOI recognition capability.