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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.

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.

We have developed a 4-layer depth-of-interaction (DOI) detector which consists of four layers of scintillation crystal arrays and a position sensitive photomultiplier tube (PS-PMT). To control the behavior of scintillation light in each DOI crystal array, some reflectors between crystals are removed so that all crystal responses in the four layers are expressed in one two-dimensional (2D) position histogram by implementing an Anger-type calculation of the PS-PMT signals. Since the method utilizes spread of scintillation light through the boundary of the crystals with no reflectors, positioning performance in the 2D position histogram depends on the crystal dimensions, the crystal surface finish, and gap materials. In this work, we propose an adjustment method for crystal identification performance of the 4-layer DOI detector by selecting the optimal refractive index for the gap materials between the crystals in which the reflectors are removed. We fabricated single-layer detectors and 4-layer detectors using LYSO scintillators and evaluated the crystal identification performance, while varying the refractive index of the gap materials (by using different optical cements). As a result, we found the 2D position histogram changes as a function of the refractive index of the optical cement between crystals and the optimal refractive indices can be determined for the detector using the LYSO crystals. We concluded that the crystal response of the 2D position histograms can be adjusted and crystal identification performance can be optimized by changing the refractive index of the gap materials.

We are developing a PET-MRI system which consists of PET detectors integrated with the head coil of the MRI in order to realize high spatial resolution and high sensitivity in simultaneous measurements. In the PET-MRI system, the PET detectors which consist of a scintillator block, photo-detectors and front-end circuits with four-layer depth-of-interaction (DOI) encoding capability are placed close to the measured object. Therefore, the proposed system can achieve high sensitivity without degradation of spatial resolution at the edge of the field-of-view due to parallax error thanks to the four-layer DOI capability. In this paper, we fabricated a prototype system which consists of a prototype four-layer DOI-PET detector, a dummy PET detector and a prototype birdcage type head coil. Then we used the prototype system to evaluate the performance of the four-layer DOI-PET detector and the reciprocal influence between the PET detectors and MRI images. The prototype DOI-PET detector consists of six monolithic multi-pixel photon counter (MPPC) arrays (S11064-050P), a readout circuit board, two scintillator blocks and a copper shielding box. Each scintillator block consists of four layers of Lu1.8Gd0.2SiO5:Ce (LGSO) scintillators and reflectors are inserted between the scintillation crystals. The dummy detector has all these components except the two scintillator blocks. The head coil is dedicated to a 3.0 T MRI (MAGNETOM Verio, Siemens) and the two detectors are mounted in gaps between head coil elements. Energy resolution and crystal identification performance of the prototype four-layer DOI-PET detector were evaluated with and without MRI measurements by the gradient echo and spin echo methods. We identified crystal elements in all four layers from a 2D flood histogram and energy resolution of 15–18% was obtained for single crystal elements in simultaneous measurements. The difference between the average energy resolutions and photo-peak positions with and without MRI measurements was lower than 0.3 percentage points and 1.7% for all layers. The results indicated that these performances were sufficient as PET detectors for the proposed PET-MRI system and there was no influence from the MRI measurements on the PET imaging in the simultaneous measurements. The signal-to-noise ratio of the MRI image and static magnetic field of the MRI were also evaluated with and without measurements of the PET detectors. The maximum decrease of the static magnetic field due to the LGSO scintillators was approximately 1 ppm. The signal-to-noise ratio decreased from 242.80 without the PET detector to 44.948 in simultaneous measurements.

Dose and range verification have become important tools to bring carbon ion therapy to a higher level of confidence in clinical applications. Positron emission tomography is among the most commonly used approaches for this purpose and relies on the creation of positron emitting nuclei in nuclear interactions of the primary ions with tissue. Predictions of these positron emitter distributions are usually obtained from time-consuming Monte Carlo simulations or measurements from previous treatment fractions, and their comparison to the current, measured image allows for treatment verification. Still, a direct comparison of planned and delivered dose would be highly desirable, since the dose is the quantity of interest in radiation therapy and its confirmation improves quality assurance in carbon ion therapy. In this work, we present a deconvolution approach to predict dose distributions from PET images in carbon ion therapy. Under the assumption that the one-dimensional PET distribution is described by a convolution of the depth dose distribution and a filter kernel, an evolutionary algorithm is introduced to perform the reverse step and predict the depth dose distribution from a measured PET distribution. Filter kernels are obtained from either a library or are created for any given situation on-the-fly, using predictions of the positron emitter (B+) decay and depth dose distributions, and the very same evolutionary algorithm. The applicability of this approach is demonstrated for monoenergetic and polyenergetic carbon ion irradiation of homogeneous and heterogeneous solid phantoms as well as a patient computed tomography image, using Monte Carlo simulated distributions and measured in-beam PET data. Carbon ion ranges are predicted within less than 0.5 mm and 1 mm deviation for simulated and measured distributions, respectively.

© 2019 Commonwealth of Australia, Australian Nuclear Science and Technology Organisation, ANSTO.. The distribution of fragmentation products predicted by Monte Carlo simulations of heavy ion therapy depend on the hadronic physics model chosen in the simulation. This work aims to evaluate three alternative hadronic inelastic fragmentation physics options available in the Geant4 Monte Carlo radiation physics simulation framework to determine which model most accurately predicts the production of positron-emitting fragmentation products observable using in-beam PET imaging. Fragment distributions obtained with the BIC, QMD, and INCL + + physics models in Geant4 version 10.2.p03 are compared to experimental data obtained at the HIMAC heavy-ion treatment facility at NIRS in Chiba, Japan. For both simulations and experiments, monoenergetic beams are applied to three different block phantoms composed of gelatin, poly(methyl methacrylate) and polyethylene. The yields of the positron-emitting nuclei 11C, 10C and 15O obtained from simulations conducted with each model are compared to the experimental yields estimated by fitting a multi-exponential radioactive decay model to dynamic PET images using the normalised mean square error metric in the entrance, build up/Bragg peak and tail regions. Significant differences in positron-emitting fragment yield are observed among the three physics models with the best overall fit to experimental 12C and 16O beam measurements obtained with the BIC physics model.

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 11C and 15O 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 11C and 15O. 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 11C and 15O 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 11C ion beams compared to 15O 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.

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.

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.

Insertion sequences (ISs) are the simplest transposable elements and are widely distributed in bacteria; however, they also play important roles in genome evolution. We recently identified a protein called IS excision enhancer (IEE) in enterohemorrhagic Escherichia coli (EHEC) O157. IEE promotes the excision of IS elements belonging to the IS 3 family, such as IS 629 , as well as several other families. IEE-mediated IS excision generates various genomic deletions that lead to the diversification of the bacterial genome. IEE has been found in a broad range of bacterial species; however, among sequenced E. coli strains, IEE is primarily found in EHEC isolates. In this study, we investigated non-EHEC pathogenic E. coli strains isolated from domestic animals and found that IEE is distributed in specific lineages of enterotoxigenic E. coli (ETEC) strains of serotypes O139 or O149 isolated from swine. The iee gene is located within integrative elements that are similar to SpLE1 of EHEC O157. All iee -positive ETEC lineages also contained multiple copies of IS 629 , a preferred substrate of IEE, and their genomic locations varied significantly between strains, as observed in O157. These data suggest that IEE may have been transferred among EHEC and ETEC in swine via SpLE1 or SpLE1-like integrative elements. In addition, IS 629 is actively moving in the ETEC O139 and O149 genomes and, as in EHEC O157, is promoting the diversification of these genomes in combination with IEE.

Several MRI-based attenuation correction methods have been reported for PET/MRI; these methods are expected to make efficient use of high-quality anatomical MRIs and reduce the radiation dose for PET/MRI scanning. The accuracy of the attenuation map (μ-map) from an MRI depends on the accuracy of tissue segmentation and the attenuation coefficients to be assigned (μ-values). In this study, we proposed an MRI-based μ-value estimation method with a non-rotational radiation source to construct a suitable μ-map for PET/MRI. The proposed method uses an accurately segmented tissue map, the partial path length of each tissue, and detected intensities of attenuated radiation from a fixed-position (rather than a rotating) radiation source to obtain the μ-map. We estimated the partial path length from a virtual blank scan of fixed-point radiation with the same scanner geometry using the known tissue map from MRI. The μ-values of every tissue were estimated by inverting a linear relationship involving the partial path lengths and measured radioactivity intensity. Validation of the proposed method was performed by calculating a fixed- point data set based upon real a real transmission scan. The root-mean-square error between the μ-values derived from a conventional transmission scan and those obtained with our proposed method were 2.4±1.4%, 17.4±9.1% and 6.6±4.3% for brain, bone and soft tissue other than brain, respectively. Although the error estimates for bone and soft tissue are not insignificant, the method we propose is able to estimate the brain μ-value accurately and it is this factor that most strongly affects the quantitative value of PET images because of the large volumetric ratio of the brain.

An 18-week-old female breeding Yorkshire pig displayed symptoms of astasia and subsequently died. Histologically, severe disseminated suppurative meningoencephalomyelitis was detected, as were numerous myocardial microabscesses. Gram-positive cocci were detected in these suppurative lesions, and these cocci reacted with an antibody against Streptococcus C group species. Gram-positive cocci were isolated from the liver, spleen, kidney, heart, lungs, pleural abscess and articular fluid of the right tarsal joint. The isolates were β-hemolytic, categorized into Lancefield group C and were identified as Streptococcus dysgalactiae subspecies equisimilis by analysis of the 16S ribosomal DNA sequence. This is the first report of systemic S. equisimilis infection in a pig with severe disseminated suppurative meningoencephalomyelitis.

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 have developed a three-dimensional (3-D) position-sensitive radiation detector named X'tal cube, which can be applied to a PET detector. The X'tal cube is composed of a scintillation crystal block and multi-pixel photon counters (MPPCs). The crystal block is segmented three-dimensionally into small cubes by optical discontinuity (3-D segmentation) and no reflector is inserted inside. Scintillation light originating in a segment then spreads three-dimensionally so that the MPPCs are set on all six surfaces of the crystal block to detect the light. Regarding the 3-D segmentation of the crystal block, we have already succeeded in getting the segmentation inside of a monolithic scintillator block by a laser processing technique instead of the general way, arranging small cubic scintillator elements into a 3-D array. We have confirmed that utilizing the laser processing technique not only eliminates the difficulty of handling the small scintillator elements but also improves detector performance. As a new trial, we considered fabrication of the crystal block by stacking the scintillator plates which were segmented two-dimensionally by the laser processing technique (2-D segmentation). Plates are also easier to handle and for the laser processing, 2-D segmentation is simpler than 3-D segmentation. In this study, we prepared the X'tal cube with the scintillator plates (Plate-XC) and evaluated its performance to confirm its technical feasibility. For the Plate-XC, we segmented 18 mm × 18 mm × 2.0 mm LYSO plates two-dimensionally by laser processing so as to make a 9 × 9 array of 2.0 mm × 2.0 mm segments. The crystal block was composed of 9 stacked LYSO plates without using coupling material but with air gaps. The Plate-XC showed sufficient crystal identification performance when 662 keV gamma-rays were irradiated. Furthermore, to understand the characteristics of the Plate-XC, we also analyzed the scintillation light distribution in the crystal block. Results indicated that light spread from outer segments was influenced by the segment boundary conditions, air gaps or laser-processed gaps, while the spread from the center segment did not seem to have such an influence. Regarding energy performance, we obtained around 10% energy resolution for the outer segments as well as for the center segment.

Silicon photomultipliers (SiPMs) provide many advantages for PET detectors, such as their high internal gain, high photon detection efficiency and insensitivity to magnetic fields. The number of detectable scintillation photons of SiPMs, however, is limited by the number of microcells. Therefore, pulse height of PET detectors using SiPMs is saturated when large numbers of scintillation photons enter the SiPM pixels. On the other hand, we previously presented a depth-of-interaction (DOI) encoding method that is based on the light sharing method. Since our encoding method detects scintillation photons with multiple readout pixels, the saturation effect can be suppressed. We constructed two prototype four-layer DOI detectors using a SiPM array and evaluated their performances. The two prototype detectors consisted of four layers of a 6×6 array of Lu 2(1− x ) Y 2 x SiO 5 (LYSO) crystals and a SiPM (multi-pixel photon detector, MPPC, Hamamatsu Photonics K.K.) array of 4×4 pixels. The size of each LYSO crystal element was 1.46 mm×1.46 mm×4.5 mm and all surfaces of the crystal elements were chemically etched. We used two types of MPPCs. The first one had 3600 microcells and high photon detection efficiency (PDE). The other one had 14,400 microcells and lower PDE. In the evaluation experiment, all the crystals of the detector using the MPPC which had the high PDE were clearly identified. The respective energy and timing resolutions of lower than 15% and 1.0 ns were achieved for each crystal element. No saturation of output signals was observed in the 511 keV energy region due to suppression of the saturation effect by detecting scintillation photons with several MPPC pixels by the light sharing method.

Positron emission tomography (PET) has become a popular imaging method in metabolism, neuroscience, and molecular imaging. For dedicated human brain and small animal PET scanners, high spatial resolution is needed to visualize small objects. To improve the spatial resolution, we are developing the X’tal cube, which is our new PET detector to achieve isotropic 3D positioning detectability. We have shown that the X’tal cube can achieve 1 mm 3 uniform crystal identification performance with the Anger-type calculation even at the block edges. We plan to develop the X’tal cube with even smaller 3D grids for sub-millimeter crystal identification. In this work, we investigate spatial resolution of a PET scanner based on the X’tal cube using Monte Carlo simulations for predicting resolution performance in smaller 3D grids. For spatial resolution evaluation, a point source emitting 511 keV photons was simulated by GATE for all physical processes involved in emission and interaction of positrons. We simulated two types of animal PET scanners. The first PET scanner had a detector ring 14.6 cm in diameter composed of 18 detectors. The second PET scanner had a detector ring 7.8 cm in diameter composed of 12 detectors. After the GATE simulations, we converted the interacting 3D position information to digitalized positions for realistic segmented crystals. We simulated several X’tal cubes with cubic crystals from (0.5 mm) 3 to (2 mm) 3 in size. Also, for evaluating the effect of DOI resolution, we simulated several X’tal cubes with crystal thickness from (0.5 mm) 3 to (9 mm) 3 . We showed that sub-millimeter spatial resolution was possible using cubic crystals smaller than (1.0 mm) 3 even with the assumed physical processes. Also, the weighted average spatial resolutions of both PET scanners with (0.5 mm) 3 cubic crystals were 0.53 mm (14.6 cm ring diameter) and 0.48 mm (7.8 cm ring diameter). For the 7.8 cm ring diameter, spatial resolution with 0.5×0.5×1.0 mm 3 crystals was improved 39% relative to the (1 mm) 3 cubic crystals. On the other hand, spatial resolution with (0.5 mm) 3 cubic crystals was improved 47% relative to the (1 mm) 3 cubic crystals. The X’tal cube promises better spatial resolution for the 3D crystal block with isotropic resolution.

The X'tal cube is our original PET detector, which is being developed to achieve isotropic 3D positioning detectability. The X'tal cube is based on a 3D segmented crystal block for which all surfaces are covered with photo-detectors. Previously, instead of our initial approach of gluing segmented pieces of crystals, we successfully constructed a crystal block segmented by laser processing, and we developed the X'tal cube with the laser-processed 3D square grids of 2 mm length. In this paper, we extend the laser processing to 3D square grids of 1 mm length. The volume of a 1-mm crystal segment is 1/8 of that of a 2-mm crystal segment. We also evaluate imaging resolution performance with a newly developed one-pair prototype system to simulate a ring-type scanner, while our previous reports were limited to development and evaluation of a single detector. In particular, we compare 1-mm X'tal cube detectors to 2-mm X'tal cube detectors. The one-pair prototype system consisted of two X'tal cubes, two rotating stages, and a 192-channel data acquisition system. Each X'tal cube consisted of the LYSO cubic crystal block of 18 × 18 × 18 mm3 in which the 3D grids of 1 mm pitch were fabricated by internal laser processing. The 4 × 4 arrays of multi pixel photon counters were optically coupled to each surface of the crystal block. The detector positions were automatically controlled to simulate a ring-type PET with a 14.6 cm diameter. Data were collected for all assumed detector positions and then a sinogram was obtained. The data were reconstructed using filtered backprojection. The average spatial resolution of the 2-mm X'tal cube was 1.9 mm full width at half maximum (FWHM) over the field-of-view (FOV). On the other hand, the average spatial resolution of the 1-mm X'tal cube was 1.3 mm FWHM over the FOV. By applying deconvolution with the assumption that the point source was a Gaussian function of 1.0 mm FWHM, we estimated the average spatial resolution of the 2-mm X'tal cube and the 1-mm X'tal cube as 1.6 mm FWHM and 0.83 mm FWHM, respectively. The average spatial resolution of the 1-mm X'tal cube was improved approximately 48% compared to the 2-mm X'tal cube. In conclusion, we confirmed the potential of the X'tal cube for uniform and high resolution imaging.

A conventional PET scanner has a 15–25 cm axial field-of-view (FOV) and images the whole body using about six bed positions. We proposed our original OpenPET geometry which can extend the axial FOV with a limited number of detectors. For an alternative approach, we then designed an axially extendable multiplex cylinder (AEMC) PET scanner to provide high versatility for clinical and research studies using a silicon-photomultiplier (Si-PM)-based DOI detector. Since Si-PMs have high gain like PMTs and a compact design, the Si-PM-based detector is expected to enable various new detector arrangements. The AEMC-PET scanner consists of four independent and laminated detector rings using a four-layer depth-of-interaction (DOI) detector. This PET scanner can extend the axial FOV as each stacked detector ring can be slid aside. When this scanner is used for the four-layer DOI detector, its minimum axial FOV is 24 cm and its maximum crystal thickness is 3 cm. On the other hand, the axial FOV can be extended to 96 cm while keeping a continuous axial FOV, but the crystal thickness must be 1/4 of 3 cm. In addition, using the OpenPET geometry, the axial FOV can be extended to 168 cm. In this work, we studied the feasibility of the PET scanner with a variable axial FOV using Monte Carlo simulation. For the 180-cm line source simulation, the 96-cm axial FOV was obtained with twofold better sensitivity compared to the 24-cm axial FOV. Also, we showed that the AEMC-PET scanner had a continuous axial FOV to 168 cm. We expect the AEMC-PET scanner will provide high versatility such as for measuring trace whole-body uptakes while keeping the continuous axial FOV and the scan time for static images will be reduced with a limited number of detectors., 2012IEEE NSS&MIC

One of the challenging applications of PET is implementing it for in-beam PET, which is an in situ monitoring method for charged particle therapy. For this purpose, we have previously proposed an open-type PET scanner, OpenPET. The original OpenPET had a physically opened field-of-view (FOV) between two detector rings through which irradiation beams pass. This dual-ring OpenPET (DROP) had a wide axial FOV including the gap. This geometry was not necessarily the most efficient for application to in-beam PET in which only a limited FOV around the irradiation field is required. Therefore, we have proposed a new single-ring OpenPET (SROP) geometry which can provide an accessible and observable open space with higher sensitivity and a reduced number of detectors than the DROP. The proposed geometry was a cylinder shape with its ends cut at a slant, in which the shape of each cut end became an ellipse. In this work, we developed and evaluated a small prototype of the SROP geometry for proof-of-concept. The SROP prototype was designed with 2 ellipse-shaped detector rings of 16 depth-of-interaction (DOI) detectors each. The DOI detectors consisted of 1024 GSOZ scintillator crystals which were arranged in 4 layers of 16×16 arrays, coupled to a 64-channel FP-PMT. Each ellipse-shaped detector ring had a major axis of 281.6 mm and a minor axis of 207.5 mm. For the slant mode, the rings were placed at a 45-deg slant from the axial direction and for the non-slant mode (used as a reference) they were at 90 deg from the axial direction with no gap. The system sensitivity measured from a 22 Na point source was 5.0% for the slant mode. The average spatial resolutions of major and minor axis directions were calculated as 3.8 mm FWHM and 4.9 mm FWHM, respectively for the slant mode. This difference resulted from the ellipsoidal ring geometry and the spatial resolution of the minor axis direction degraded by the parallax error. Comparison between the slant mode and the non-slant mode showed no remarkable difference in terms of the sensitivity distribution and spatial resolution performance. Therefore, we concluded that the SROP geometry has a good potential as an open geometry especially suitable for in-beam imaging.

Aim The present study examined the effect of irritable bowel syndrome (IBS), cognitive appraisal of IBS, and anxiety sensitivity on anticipatory anxiety (AA) and agoraphobia (AG) in patients with panic disorder (PD). Methods We examined 244 PD patients who completed a set of questionnaires that included the Rome II Modular Questionnaire to assess the presence of IBS, the Anxiety Sensitivity Index (ASI), the Cognitive Appraisal Rating Scale (CARS; assessing the cognitive appraisal of abdominal symptoms in four dimensions: commitment, appraisal of effect, appraisal of threat, and controllability), and items about the severity of AA and AG. The Mini International Neuropsychiatric Interview was used to diagnose AG and PD. Results After excluding individuals with possible organic gastrointestinal diseases by using ‘red flag items,’ valid data were obtained from 174 participants, including 110 PD patients without IBS (PD/IBS[–]) and 64 with IBS (PD/IBS[+]). The PD/IBS[+] group had higher AA and higher comorbidity with AG than the PD/IBS[–] group. In the PD/IBS[+] group, the controllability score of CARS was significantly correlated with AA and ASI. Multiple regression analysis showed a significant effect of ASI but not of controllability on AA in PD/IBS[+] subjects. Conclusion This study suggested that the presence of IBS may be related to agoraphobia and anticipatory anxiety in PD patients. Cognitive appraisal could be partly related to anticipatory anxiety in PD patients with IBS with anxiety sensitivity mediating this correlation.

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 six sides of the crystal block. The X'tal cube is composed of a 3D crystal block with isotropic segments. Each face of the 3D crystal block is covered with a 4×4 array of multi-pixel photon counters (MPPCs). Previously, in order to fabricate the 3D crystal block efficiently and precisely, we applied a sub-surface laser engraving technique to a monolithic crystal block instead of gluing segmented small crystals. A dense arrangement of multiple micro-cracks carved by the laser beam works efficiently as a scattering wall for the scintillation photons. The X'tal cube with the laser-processed block showed excellent performance with respect to crystal identification and energy resolution. In this work, for characteristics comparison between the laser-processed block and the conventional segmented array block, we made the laser-processed block and two types of segmented array blocks, one with air gaps and the other with glued segmented small crystals. All crystal blocks had 3D grids of 2 mm pitch. The 4×4 MPPC arrays were optically coupled to each surface of the crystal block. When performance was evaluated using a uniform irradiation of 511 keV, we found that the X'tal cubes with the laser-processed block could easily achieve 2 mm 3 uniform crystal identification. Also, the average energy resolution of each 3D grid was 11.1±0.7%. On the other hand, the glued segmented array block had a pinched distribution and crystals could not be separated clearly. The segmented array block with air gaps had satisfactory crystal identification performance; however, the laser-processed block had higher crystal identification performance. Also, the energy resolution of the laser-processed block was better than for the segmented array blocks. In summary, we found the laser-processed X'tal cube had excellent crystal identification performance and high energy performance due to its effective dense arrangement of micro-cracks.

Protein adsorption onto titanium (Ti) or zirconia (ZrO2) was evaluated using a 27 MHz quartz crystal microbalance (QCM). As proteins, fibronectin (Fn), a cell adhesive protein, and albumin (Alb), a cell adhesion-inhibiting protein, were evaluated. The Ti and ZrO2 sensors for QCM were characterized by atomic force microscopy and electron probe microanalysis observation, measurement of contact angle against water, and surface roughness. The amounts of Fn and Alb adsorbed onto the Ti and ZrO2 sensors and apparent reaction rate were obtained using QCM measurements. Ti sensor showed greater adsorption of Fn and Alb than the ZrO2 sensor. In addition, amount of Fn adsorbed onto the Ti or ZrO2 sensors was higher than that of Alb. The surface roughness and hydrophilicity of Ti or ZrO2 may influence the adsorption of Fn or Alb. With regard to the adsorption rate, Alb adsorbed more rapidly than Fn onto Ti. Comparing Ti and ZrO2, Alb adsorption rate to Ti was faster than that to ZrO2. Fn adsorption will be effective for cell activities, but Alb adsorption will not. QCM method could simulate in vivo Fn and Alb adsorption to Ti or ZrO2.

Positron emission tomography (PET) has become a popular imaging method in metabolism, neuroscience, and molecular imaging. For dedicated human brain and small animal PET scanners, high spatial resolution is needed to visualize small objects. To improve PET resolution, we are developing X'tal cube, which is our new PET detector to achieve isotropic 3D positioning detectability. It consists of a segmented 3D crystal block of which all surfaces are covered with semiconductor photo-sensors. We have shown that the X'tal cube can achieve (1 mm)3 uniform crystal identification performance. To improve further spatial resolution, we intend to develop the sub-millimeter X'tal cube. However, one problem that prevents its commercial mass production is handling the small crystal pieces, i.e., cutting out and assembling them. In this work, to evaluate to benefit of the sub-millimeter X'tal cube, we simulated dedicated brain and small animal PET scanners with X'tal cubes using a Monte Carlo simulation and calculated spatial resolutions with the X'tal cubes with from (0.5 mm)3 to (1.0 mm)3 cubic crystals. For spatial resolution evaluation, a point source emitting 511 keV photons was simulated with all physical processes involved during emission and interaction of positrons. The brain PET scanner has a detector ring of 275 mm in diameter composed of 48 detectors. The small animal PET scanner has a detector ring of 82 mm in diameter composed of 14 detectors. The simulated data were projected to the sinogram and reconstructed using the 2D filtered backprojection. For the small animal PET scanner, we showed that sub-millimeter spatial resolution is possible using the X'tal cube with cubic crystals smaller than 0.9 mm even with the physical processes. On the other hand, for the brain PET scanner, spatial resolutions increased 20% larger than these of the small animal PET scanner due to the non-collinearity effect. However, for both PET scanners, we showed that the spatial resolution significantly improved, as cubic crystals were smaller.

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.

Initial stage of biofilm formation is the adhesion of salivary pellicle proteins on the material surfaces. The aim of the present study was to evaluate the adsorption behaviors of saliva pellicle proteins onto a gold, silica and titanium by using the 27 MHz quartz crystal microbalance method. As pellicle proteins, lactoferrin, lysozyme, defensin and mucin were evaluated. Adsorption amount of lactoferrin to silica was significantly lower than gold and titanium. Significant differences were detected between titanium and silica for the adsorption amounts of lysozyme. Chemical bond formation of sulfur atom of lysozyme and gold could be suggested. There were no significant differences of the adsorption amount of β-defensin among each substrate. For mucin adsorption, gold showed the highest adsorption amount. It is presumed that electrostatic repulsion caused less adsorption amounts of mucin to titanium and silica. In conclusion, the differences of the adsorption behaviors of pellicle proteins could be clearly identified.

We developed a modified, more practical four-layered depth-of-interaction (DOI) detector based on the light sharing method. Reflectors, which are inserted in every two lines of crystal segments and shifted differently depending on each layer, project 3-D crystal positions onto a 2-D position histogram without any overlapping after applying an Anger-type calculation. The best crystal separation we have ever made based on this method was the 4-layered 32 × 32 array of LYSO crystals sized at 1.45 × 1.45 × 5 mm3. However, assembling crystals of a tiny size tends to cost a lot, and fine tuning of the light guide and the front-end circuit is required to have fine crystal identification from photo sensor signals of coarser pixel pitch. In this paper, therefore, we proposed a more practical 4-layered DOI detector. The key idea is that the crystals in the top layer, which have the highest detection efficiency, mostly contribute to PET spatial resolution. We applied two new ideas: (1) use of 1/4 size crystals only for the 1st (top) layer and (2) inserting a thin light guide between the 1st and the 2nd layers of crystal array. In the developed prototype detector, the 1st layer used 32 × 32 LYSO crystals of quarter size (1.4 × 1.4 × 5.0 mm3) compared with the other layers (16 × 16 arrays of crystals of 2.8 × 2.8 × 5.0 mm3). For better crystal identification of small crystals in the 1st layer, we optimized the optical condition between crystals such as use of an optical glue or air. Also, a thin light guide was inserted between the 1st and the 2nd layers for improvement of crystal identification of the 1st layer. With the appropriate insertion of the light guide, all crystals of the 1st layer were identified as well as the crystals in the other layers.

High sensitivity, high spatial resolution and low cost dedicated brain PET scanners are required for early diagnosis of Alzheimer's disease and brain function studies. As an optimal geometry, we proposed and developed the first prototype of the helmet-chin PET scanner. The scanner was constructed from 4-layer DOI detectors constructed from GSO crystals which were originally developed for our OpenPET. The helmet part of the helmet-chin PET consisted of three ring detectors with different radii arranged on a surface of a hemisphere and a top cover. In this study, for our next development, we optimized the size of the detectors to be arranged on the helmet, and compared two types of geometrical arrangements of the detectors on the hemisphere: a spherical arrangement in which the center of each detector faces toward the center of the hemisphere, and a multi-ring arrangement which has a similar detector arrangement to that of the first prototype. Geant4 simulation toolkit was used to model the scanners. The simulated scanners were constructed from LYSO crystals with a size of 1 × 1 × 5 mm3 (transaxial × axial × DOI). A dead-space of 2 mm was assumed in the axial and transaxial directions of the detector such as for wrapping. While fixing the number of the DOI layers to 4, the size of the detectors was varied by changing the number of crystals in the transaxial and axial directions. The results showed that, for the helmet detector, a detector with a size of 42 × 42 × 20 mm3 had the highest sensitivity evaluated using a hemispherical phantom. Then, the helmet-chin PET was modeled based on a detector whose size is 42 × 42 × 20 mm3 with the two geometrical arrangements and their sensitivities were compared. The respective sensitivities for hemispherical and multi-ring arrangements were 3.4% and 2.9% for a hemispherical phantom.

PET is the most sensitive imaging technique in the field of nuclear medicine. However, the single count rate is typically 10 times higher than the coincidence count rate. This means that there are a lot of pairs of undetected annihilation photons. For single gamma imaging, Compton imaging is known as the only method to obtain directional information of an incoming gamma ray without using collimators. Compton kinematics collimation suffers from poor angular resolution due to Doppler broadening, energy blurring, and position blurring. Therefore, Compton imaging is still challenging compared to PET imaging in general. However, non-coincidence single photons have the potential to contribute to improved imaging performance. Previously, we have proposed a system which combines PET and Compton imaging and we showed high sensitivity of this system using Compton kinematics collimation events. In this paper, we evaluate sensitivity and spatial resolution for feasibility of this system. This system modeled the PET ring and the inserted Compton scatter ring. The PET ring consisted of 48 DOI detectors arranged in five rings with a ring diameter of 80 cm. The PET ring was made of GAGG with a size of 2.9 × 2.9 × 5 mm3 including 4-layered DOI capability. Ring diameters of the scatter ring were selected as 30, 40, 50 and 60 cm. Detector material of the scatter ring was Si with a pixel size of 0.9 × 0.9 × 0.6 mm3. From point source measurements, images of PET and Compton events were individually reconstructed by the 3D-LM-OSEM algorithm. From point source measurements at the center of the field-of-view, spatial resolution with 30 cm diameter was 3 mm. Also, as the position of the point source was close to the detector, spatial resolution was improved. The proposed system had a potential of high spatial resolution for not only PET imaging but also Compton imaging with the small scatter ring.

We are developing a PET/MRI system based on 4-layered depth-of-interaction (DOI) detectors integrated with a birdcage RF-coil. The PET detectors are placed close to the objective to achieve both high sensitivity and high spatial resolution even at the edge of the field of view (FOV). In a previous study, we reported the first prototype which had a single detector ring to show a proof-of-concept and lower than 1.6 mm spatial resolution was achieved. However, the axial FOV of the prototype was only 1 cm, which could not be extended due to the size of the readout circuit boards. In this paper, we finally constructed a new RF-coil for the second prototype, which is combined with 24 DOI-PET detectors. We evaluated performance in simultaneous measurements. The second prototype consisted of an RF-coil and 24 PET detector units with two PET detectors each. The detector units were shielded with carbon fiber shielding boxes. Each PET detector consisted of a 14 × 14 × 4-layer array of lutetium fine silicate (LFS) crystals (1.9 mm × 1.9 mm × 4.0 mm), an 8 × 8 multi-pixel photon counter module (MPPC, S11206-0808FC(X)) and a readout circuit board with an ASIC. The RF coil was dedicated to a 3T MRI (MAGNETOM Verio, Siemens). We conducted performance tests of the second prototype in simultaneous measurements. As a result, the influence of the MRI measurements on the PET performance was found to be negligible. In addition, secondary magnetic field due to the eddy current effect can be reduced, compared with the previous prototype system.

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.

In positron emission tomography (PET), 3D iterative image reconstruction methods have a huge computational burden. In this paper, we developed a list-mode image reconstruction method using graphics processing units (GPUs). Efficiency of acceleration for GPU implementation largely depends on the method chosen, where a reduced number of conditional statements and a reduced memory size are required. On the other hand, accurate system models are required to improve the quality of reconstructed images. Various accurate system models for conventional CPU implementation have been proposed, but these models basically require many conditional statements and huge memory size. Therefore, we developed a new system model which matches GPU implementation better. In this model, the detector response functions, which vary depending on each line of response (LOR), are pre-computed in CPUs and modeled by sixth-order polynomial functions in order to reduce the memory size occupied in GPUs. Each element of a system matrix is obtained on-the-fly in GPUs by calculating the distance between an LOR and a voxel. Therefore the developed system model enables efficient GPU implementation of the accurate system modeling with a reduced number of conditional statements and a reduced memory size. We applied the developed method to a small OpenPET prototype, in which 4-layered depth-of-interaction (DOI) detectors were used. For image reconstruction, we used the dynamic row-action maximum likelihood algorithm (DRAMA). Compared with a conventional model for GPU implementation, in which DRFs are given as a Gaussian function of fixed width, we saw no remarkable difference for DOI data, but for non-DOI data the proposed model outperformed the conventional at the peripheral region of the field-of-view. The proposed model had almost the same calculation time as the conventional model did. For further acceleration, we tried parallel GPU implementation, and we obtained 3.8-fold acceleration by using 4 GPUs.

We develop an OpenPET system which can provide an accessible open space to the patient during PET scanning. Our first-generation OpenPET geometry which we called dual-ring OpenPET consisted of two separated detector rings and it could extend its axial field of view (FOV) therefore enabling imaging the gap region in addition to the in-ring region. However, applications such as dose verification by in-beam PET measurement during particle therapy and real-time tumor tracking by PET require sensitivity focused onto the gap rather than on the wide FOV. In this paper, we propose a second-generation OpenPET geometry, single-ring OpenPET, which can provide an accessible and observable open space with higher sensitivity and a reduced number of detectors than the earlier one. The proposed geometry has a cylinder shape cut at a slant angle, in which the shape of each cut end becomes an ellipse. We provided a theoretical analysis for sensitivity of the proposed geometry, compared with the dual-ring OpenPET and a geometry where the conventional PET was positioned at a slant angle against the patient bed to form an accessible open space, which we called a slant PET. The central sensitivity depends on the solid angle of these geometries. As a result, we found that the single-ring OpenPET has a sensitivity 1.2 times higher than the dual-ring OpenPET and 1.3 times higher than the slant PET when designed for a 600 mm bed width with 300 mm accessible open space and about 200 detector blocks, each with a front area of 2500 mm². In addition, numerical simulation was carried out to show the imaging property of the proposed geometry realized with the ellipsoidal rings and these results indicate that the depth-of-interaction detector can provide uniform resolution even when the detectors are arranged in an ellipsoidal ring.

We have developed a new three-dimensional (3D) position sensitive radiation detector, called the X'tal cube. The X'tal cube is composed of a scintillation crystal block and a number of multi-pixel photon counters (MPPCs) which are coupled on all six sides of the block. The block is segmented into cubes and no reflector is used between the segments. Scintillation light originating in a crystal segment accordingly propagates three-dimensionally along the alignment of the crystal segments and is efficiently detected by the MPPCs. The X'tal cube could be used as the detector element of a PET system, for instance. We constructed two prototypes of the X'tal cube and evaluated their performance using gamma-ray sources. The crystal block of each prototype is composed of a 3D array of Lu2xGd2(1-x)SiO5: Ce (LGSO, x = 0.9) crystal segments. Each crystal volume is 3.0 mm x 3.0 mm x 3.0 mm. MPPCs of a 3.0 mm x 3.0 mm active area are coupled to each surface of the crystal block. In this work, we show that all crystal segments are identified by a simple Anger-type calculation performed on the MPPC signals for both prototypes. The X'tal cube provides high spatial resolution in three dimensions regardless of the incident angle of the radiation.

The aim of the present study was to evaluate the influence of mechanical treatment, namely, nanometer smoothing (Ra: approximately 2.0 nm) and sandblasting (Ra: approximately 1.0 μm), as well as biochemical treatment, namely, fibronectin immobilization, of a titanium surface on osteoblast-like cell behavior. Cell proliferation was monitored by measurements of DNA content and ALP activity; osteocalcin production and mineralization behavior were also evaluated, in addition to morphological observation of attached cells. Fibronectin could be immobilized by the tresyl chloride-activation method. A sandblasted surface resulted in significantly more DNA than a nanometer-smooth surface, but fibronectin immobilization did not result in a significant increase of DNA at 52 days of cell culture. The nanometer-smooth surface showed highest ALP activity and osteocalcin production. FN immobilization decreased ALP activity for the nanometer-smooth surface, but increased it for the sandblasted surface. The nanometer-smooth surface also showed the highest osteocalcin production. Scanning electron microscopy showed interesting phenomena of the attached cells. Attached cell area was more rapidly increased on the nanometer-smooth surface than on the sandblasted surface. It was suggested that cultured cells on the nanometer-smooth surface began to spread earlier and that the proportion of spreading cells among total attached cells increased sooner on the nanometer-smooth surface than on the sandblasted rough surface. It appeared that FN immobilization influenced the arrangement of attached cells. In conclusion, the nanometer-smooth surface employed in the present study was beneficial for the differentiation of MC3T3-E1 cells. FN immobilization influenced the morphologies of attached cells. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 2012.

The OpenPET and its real-time imaging capability have great potential for real-time tumor tracking in medical procedures such as biopsy and radiation therapy. For the real-time imaging system, we intend to use the one-pass list-mode dynamic row-action maximum likelihood algorithm (DRAMA) and implement it using general-purpose computing on graphics processing units (GPGPU) techniques. However, it is difficult to make consistent reconstructions in real-time because the amount of list-mode data acquired in PET scans may be large depending on the level of radioactivity, and the reconstruction speed depends on the amount of the list-mode data. In this study, we developed a system to control the data used in the reconstruction step while retaining quantitative performance. In the proposed system, the data transfer control system limits the event counts to be used in the reconstruction step according to the reconstruction speed, and the reconstructed images are properly intensified by using the ratio of the used counts to the total counts. We implemented the system on a small OpenPET prototype system and evaluated the performance in terms of the real-time tracking ability by displaying reconstructed images in which the intensity was compensated. The intensity of the displayed images correlated properly with the original count rate and a frame rate of 2 frames per second was achieved with average delay time of 2.1 s.

Family and twin studies have indicated that genetic factors have an important role in panic disorder (PD), whereas its pathogenesis has remained elusive. We conducted a genome-wide copy number variation (CNV) association study to elucidate the involvement of structural variants in the etiology of PD. The participants were 2055 genetically unrelated Japanese people (535 PD cases and 1520 controls). CNVs were detected using Genome-Wide Human SNP array 6.0, determined by Birdsuite and confirmed by PennCNV. They were classified as rare CNVs (found in

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.

A strong demand is expected for high-sensitivity, high-resolution and low-cost brain positron emission tomography (PET) imaging for early diagnosis of dementia, as well as for general neuroscience studies. Therefore, we have proposed novel geometries of a hemisphere detector arrangement for high-sensitivity brain imaging, in which an add-on detector at the chin position or neck position helps in sensitivity uniformity improvement. In this study, we developed the first prototype system for proof-of-concept using four-layer depth-of-interaction detectors, each of which consisted of 16 × 16 × 4 Zr-doped GSO crystals with dimensions of 2.8 × 2.8 × 7.5 mm3 and a high-sensitivity 64-channel flat-panel photomultiplier tube. We used 47 detectors to form a hemisphere detector with a hemisphere shape of 25 cm inner diameter and 50 cm outer diameter, and we used seven detectors for each of the add-on detectors. The total detector number of 54 was about one-fourth that of a typical whole-body PET scanner. The hemisphere detector for the prototype system was realized by multiple rings having different numbers of detectors and a cross-shaped top detector unit covering the top. Performance evaluation showed uniform spatial resolutions of 3-4 mm by the filtered back-projection method. Imaging tests of a hot-rod phantom done with an iterative method were able to resolve 2.2 mm rods. Peak sensitivity was measured as more than 10% at a region near the top of the head, which was achieved with the help of the top detector unit. In addition, using the prototype system, we performed the first FDG clinical test with a healthy volunteer. The results showed that the proposed geometries had high potential for realizing high-sensitivity, high-resolution, and low-cost brain PET imaging. As for the add-on detector position, it was shown that the neck position resulted in higher sensitivity and wider field of view (FOV) than the chin position because the add-on detector at the neck position can be placed continuously to the hemisphere detector and close to the FOV.

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.

Purpose: Point-like 22Na radioactive sources have been widely used for checking radiation detectors that measure annihilation photons and for evaluating PET scanners. We developed new types of 22Na point-like radioactive sources that are expected to be more symmetric than conventional source types in the angular distribution of the emitted photons. The purpose of this study is to use Monte Carlo simulation to investigate the basic characteristics of the photons emitted from the new type 22Na point-like radioactive sources. Methods: Two new types of 22Na point-like sources, a cylinder type and a sphere type, were considered in comparison with two conventional source types, a disk type and a cube type. The angular distribution and energy spectra of the emitted 0.511 MeV annihilation photons and 1.275 MeV gamma rays were calculated using a Monte Carlo code based on Geant4. Results: The angular distribution of the emitted photons was more symmetric in the new type point-like sources than in the conventional types. The asymmetry of the angular distribution of the unscattered 0.511 MeV annihilation photon pairs counted in coincidence was 0.1 ±0.1% and 1.6±0.1% in the sphere and cylinder types, compared with 4.1±0.1% and 22.6±0.1% for the cube and disk types. The scatter components around the 0.511 MeV photopeaks in the new source types were typically less than 2/3 and 1/2 of those in the disk and cube types, respectively. Conclusion: The new point-like 22Na sources offer a more symmetric angular distribution of the emitted photons with fewer scatter components. They are useful for applications where the symmetry of the emitted photons is crucial.