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To improve positron emission tomography (PET) image quality, depth-of-interaction (DOI) information and time-of-flight (TOF) information are key technologies. In this work, we developed the DOI-TOF detector based on our original single-ended readout scheme with the continuous layered gadolinium fine aluminum garnet (GFAG) array. The size of each GFAG crystal is $1.45\times 1.45\times 20$ mm3. The multipixel photon counter (MPPC) used as a photo sensor has a surface area of $3.0\times 3.0$ mm2. One pair of crystals coupled with a partial optical window is arranged across two MPPCs. Boundaries without the partial optical window are covered with optical reflectors. Each pair is coupled with paired MPPCs of different patterns. Crystal identification is obtained from paired MPPCs of different patterns and output rates. By limiting the spread of scintillation light, the proposed DOI detector based on the local centroid calculation was expected to improve crystal response, including the edge. For performance comparison, we prepared three discrete layers of the GFAG array with the same total thickness. For the continuous layer, the DOI resolution, the energy resolution and the timing resolution of the pair of detectors are 4.7 mm, 14%, and 402 ps, respectively. Their respective values are 29%, 20%, and 33% better than those with the three discrete layers.

In this article, we developed the novel single-end readout depth-of-interaction (DOI) detector with quadrisected crystals comparable in size to a single photo sensor. The proposed DOI detector consists of 784 gadolinium aluminum gallium garnet (GAGG) crystals, which are arranged in four layers of $14\times14$ arrays coupled with an $8\times8$ multipixel photon counter (MPPC) array. The size of each GAGG crystal is $1.45\times 1.45\times4.5$ mm3. Also, each MPPC has a surface area of $3.0\times3.0$ mm2. One pair of four-layered crystals coupled with a partial optical window is arranged across two MPPCs. Boundaries without the partial optical window are covered with optical reflectors. Light sharing is done between a pair of four-layered crystals optically coupled at one end. Each pair is coupled with paired silicon photomultipliers of different patterns. Crystal identification from each pair is obtained from the output rate of two MPPCs. From 511-keV uniform irradiation, responses of all crystal elements in the four layers can be separated clearly on a 2-D position histogram after applying the Anger calculation. Also, DOI information can be mapped to each cluster on curved lines. The energy resolution for all crystals is 9.1% after event reduction of intercrystal scatter.

Noninvasive quantification of myocardial blood flow with PET is a vital tool for detecting and monitoring of coronary artery disease. However, current standard cylindrical PET scanners are not optimized for cardiac imaging because they are designed mainly for whole-body imaging. In this study, we proposed two compact geometries, the elliptical geometry and the D-shape geometry, for cardiac-dedicated PET systems. We then evaluated their performance compared with a whole-body-size cylindrical geometry by using the Geant4 Monte Carlo simulation toolkit. In the simulation, an elliptical water phantom was scanned for 10-sec, and we calculated the sensitivity and the noise-equivalent count rate (NECR). Subsequently, a digital chest phantom was scanned for 30-sec and the coincidence data were reconstructed by in-house image reconstruction software. We evaluated the image noise in the liver region and the contrast recoveries in the heart region. Even with the limited number of detectors, the proposed compact geometries showed higher sensitivity than the whole-body geometry. The D-shape geometry achieved 47% higher NECR and 44% lower image noise compared with the whole-body cylindrical geometry. However, the contrasts in the hot area obtained by the proposed compact geometries were not as good as that obtained by the whole-body cylindrical geometry. There was no considerable difference in image quality between the elliptical geometry and the D-shape geometry. In conclusion, the compact geometries we have proposed are promising designs for a high-sensitivity and low-cost cardiac-dedicated PET system. A further study using a defect phantom model is required to evaluate the contrast of cold areas.

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

This work presents an iterative method for the estimation of the absolute dose distribution in patients undergoing carbon ion therapy, via analysis of the distribution of positron annihilations resulting from the decay of positron-emitting fragments created in the target volume. The proposed method relies on the decomposition of the total positron-annihilation distributions into profiles of the three principal positron-emitting fragment species - 11C, 10C and 15O. A library of basis functions is constructed by simulating a range of monoenergetic 12C ion irradiations of a homogeneous polymethyl methacrylate phantom and measuring the resulting one-dimensional positron-emitting fragment profiles and dose distributions. To estimate the dose delivered during an arbitrary polyenergetic irradiation, a linear combination of factors from the fragment profile library is iteratively fitted to the decomposed positron annihilation profile acquired during the irradiation, and the resulting weights combined with the corresponding monoenergetic dose profiles to estimate the total dose distribution. A total variation regularisation term is incorporated into the fitting process to suppress high-frequency noise. The method was evaluated with 14 different polyenergetic 12C dose profiles in a polymethyl methacrylate target: one which produces a flat biological dose, 10 with randomised energy weighting factors, and three with distinct dose maxima or minima within the spread-out Bragg peak region. The proposed method is able to calculate the dose profile with mean relative errors of 0.8%, 1.0% and 1.6% from the 11C, 10C, 15O fragment profiles, respectively, and estimate the position of the distal edge of the SOBP to within an average of 0.7 mm, 1.9 mm and 1.2 mm of its true location.

We investigated the adsorption of lipoteichoic acid (LTA) on titanium surfaces by using the quartz crystal microbalance (QCM) method, and confirmed the influence of mucin (MUC) pre-adsorption on LTA adsorption. Two injection methods were evaluated. Namely, Method A: single-step injection of LTA solution to the Ti sensor, and Method B: MUC solution was injected to the Ti sensor followed by LTA injection on the MUC pre-adsorbed surface. QCM measurement revealed that the adsorbed amount of LTA by Method A was low and constant regardless of the increase in LTA concentration. In contrast, the adsorption amount of LTA in Method B increased according with increasing concentration of LTA and was significantly higher than that of Method A. The hydrophobic surface after MUC pre-adsorption was presumed to contribute to the enhancement of LTA adsorption. Our results revealed that MUC pre-adsorption to Ti is necessary for LTA adsorption in living tissue.

Brain PET, which has led research in molecular imaging and diagnosis of brain cancer, epilepsy and neurodegenerative disorders, is being spotlighted again to promote earlier diagnosis of dementia with the advent of amyloid and tau tracers. To meet this demand, in this paper, we developed a brain-dedicated PET imaging device with a hemispherical detector arrangement, which provides comparable sensitivity with fewer detectors than conventional cylindrical geometries. The introduction of the time-of-flight (TOF) measurement capability was a key point for the development to get a gain in the image signal-to-noise ratio. Currently, whole-body PET scanners with around 200-400 ps coincidence resolving time (CRT) are commercially available. In order to obtain the same TOF gain which can be obtained with 400 ps CRT for a 30 cm diameter object, 267 ps CRT will be required for a 20 cm diameter object such as the human head. In this work, therefore, we aimed at developing a TOF brain-dedicated PET prototype with the hemisphere detector arrangement and the CRT faster than 267 ps. The detector was composed of a 12 × 12 lutetium fine silicate (LFS) array coupled with a 12 × 12 multi-pixel photon counter (MPPC) array. Each LFS crystal with a size of 4.14 × 4.14 × 10 mm3 was individually coupled to a separate MPPC. Singles list-mode data from each detector were stored, and coincidences were identified using a coincidence-detection software algorithm. The CRT of 245 ps was finally achieved as the system average after a fine timing correction. For image reconstruction, we implemented the list-mode TOF-OSEM. For a small rod phantom, rods of 3 mm diameter were clearly separated. Also, images of the 3D Hoffman brain phantom, which demonstrated clear contrast between gray and white matter, supported the effect of TOF information.

The depth-of-interaction detector which can identify gamma-ray detection position along the depth direction is essential for a PET scanner to reduce parallax error. The X’tal cube we have developed is composed of a scintillation crystal block segmented into cubes. Six arrays of multipixel photon counters (MPPCs) cover six surfaces of the crystal block. We developed the new X’tal cube consisting of 0.77 mm cubic segments. A (13.1 mm)3 LYSO crystal block had 3-D segmentation in a ${17 \times 17 \times 17}$ array fabricated by the laser engraving technique. $ {4 \times 4}$ MPPC arrays with a size of (13 mm)2 were used. Active area of each MPPC was (3.0 mm)2. To evaluate segment identification performance, we irradiated with gamma-rays from a 22Na source and obtained a 3-D position histogram made by the 3-D Anger-type calculation with all MPPC signals. The histogram showed 17 segments in a row can be identified clearly. Further, to measure its intrinsic spatial resolution with incident angles of 0° and 45°, gamma-rays in a fan-beam were irradiated and scanned onto the X’tal cube. Spatial resolutions of 0.74 ± 0.10 mm and 0.89 ± 0.10 mm were obtained by both scan experiments, respectively.

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 (Bo) inhomogeneity, RF field (B1) 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 Bo inhomogeneity was found, both in the central and 40-mm off-centered transverse planes, and a 5 percentage point increase of B1 field inhomogeneity was observed in the central transverse plane (from 84% without PET to 79% with PET), while B1 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.

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 mm3. 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.

Sodium-22 is a radioisotope which is typically used as a calibration point source for PET. Its half-life of 2.6 years is suitably long enough while its positron range is as small as that of 18F. However, the use of 22Na has been limited to a point-like shape. In this work, with the help of the Japan Radioisotope Association, we proposed a wider variety of 22Na sealed phantoms. As examples, we developed three types of 22Na phantoms: a 5-cm cylinder, a 60-cm flexible tube and a Derenzo-like multi-rod phantom. These were designed for PET system quality assurance and quality control (QA/QC) and performance measurements. At first, in this work, we evaluated uniformity and long-term stability of radioactivity distributions of these phantoms. These phantoms were scanned by the Biograph mCT Flow PET/CT scanner four times during 446 days. The uniformity of radioactivity distributions was evaluated by visual qualitative assessment and region-of-interest (ROI)-based quantitative assessment. In the case of the Derenzo-like phantom, we additionally scanned the phantom using the helmet-type PET prototype and Inveon small-animal PET system. In addition, we measured the radioactivity of these phantoms using the dose calibrator (Atomlab 500) six times during 300 days and we compared the measured and ideal decay curves. As a result, we found the variability of radioactivity distributions was lower than the 5% variation for the cylinder and tube phantoms. The Inveon PET visualized the smallest hot rod (1.6 mm diameter) of the Derenzo-like phantom and the radioactivity seemed to be uniformly distributed. The measured decay curves of all phantoms almost followed their respective ideal decay curve. We confirmed these phantoms have good uniformity and enough stability for PET system evaluation. They enable to evaluate and calibrate PET systems without radioactive solutions (ex. 18F).

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

The crosshair light-sharing (CLS) PET detector is our original depth-of-interaction (DOI) detector, which is based on a single-ended readout scheme with quadrisected crystals comparable in size to a photo-sensor. In this work, we developed 32 CLS PET detectors, each of which consisted of a multi-pixel photon counter (MPPC) array and gadolinium fine aluminum garnet (GFAG) crystals, and we developed a benchtop prototype of a small animal size PET. Each GFAG crystal was 1.45 × 1.45 × 15 mm3. The MPPC had a surface area of 3.0 × 3.0 mm2. The benchtop prototype had two detector rings of 16 detector blocks. The ring diameter and axial field-of-view were 14.2 cm and 4.9 cm, respectively. The data acquisition system used was the PETsys silicon photomultiplier readout system. The continuous DOI information was binned into three DOI layers by applying a look-up-table to a 2D position histogram. Also, energy and timing information was corrected using DOI information. After the calibration procedure, the energy resolution and the coincidence time resolution were 14.6% and 531 ps, respectively. Imaging test results of a small rod phantom obtained by an iterative reconstruction method showed clear separation of 1.6 mm rods with the help of DOI information.

Simultaneous measurements of multiple physiological parameters are essential for the study of brain disease mechanisms and the development of suitable therapies to treat them. In this study, we developed a measurement system for simultaneous optical imaging and PET for awake mice. The key elements of this system are the OpenPET, optical imaging and fixation apparatus for an awake mouse. The OpenPET is our original open-type PET geometry, which can be used in combination with another device because of the easily accessible open space of the former. A small prototype of the axial shift single-ring OpenPET was used. The objective lens for optical imaging with a mounted charge-coupled device camera was placed inside the open space of the AS-SROP. Our original fixation apparatus to hold an awake mouse was also applied. As a first application of this system, simultaneous measurements of cerebral blood flow (CBF) by laser speckle imaging (LSI) and [(11)C]raclopride-PET were performed under control and 5% CO2 inhalation (hypercapnia) conditions. Our system successfully obtained the CBF and [(11)C]raclopride radioactivity concentration simultaneously. Accumulation of [(11)C]raclopride was observed in the striatum where the density of dopamine D2 receptors is high. LSI measurements could be stably performed for more than 60 minutes. Increased CBF induced by hypercapnia was observed while CBF under the control condition was stable. We concluded that our imaging system should be useful for investigating the mechanisms of brain diseases in awake animal models.

In heavy-ion therapy, the stopping position of primary ions in tumours needs to be monitored for effective treatment and to prevent overdose exposure to normal tissues. Positron-emitting ion beams, such as 11C and 15O, have been suggested for range verification in heavy-ion therapy using in-beam positron emission tomography (PET) imaging, which offers the capability of visualizing the ion stopping position with a high signal-to-noise ratio. We have previously demonstrated the feasibility of in-beam PET imaging for the range verification of 11C and 15O ion beams and observed a slight shift between the beam stopping position and the dose peak position in simulations, depending on the initial beam energy spread. In this study, we focused on the experimental confirmation of the shift between the Bragg peak position and the position of the maximum detected positron-emitting fragments via a PET system for positron-emitting ion beams of 11C (210 MeV u-1) and 15O (312 MeV u-1) with momentum acceptances of 5% and 0.5%. For this purpose, we measured the depth doses and performed in-beam PET imaging using a polymethyl methacrylate (PMMA) phantom for both beams with different momentum acceptances. The shifts between the Bragg peak position and the PET peak position in an irradiated PMMA phantom for the 15O ion beams were 1.8 mm and 0.3 mm for momentum acceptances of 5% and 0.5%, respectively. The shifts between the positions of two peaks for the 11C ion beam were 2.1 mm and 0.1 mm for momentum acceptances of 5% and 0.5%, respectively. We observed larger shifts between the Bragg peak and the PET peak positions for a momentum acceptance of 5% for both beams, which is consistent with the simulation results reported in our previous study. The biological doses were also estimated from the calculated relative biological effectiveness (RBE) values using a modified microdosimetric kinetic model (mMKM) and Monte Carlo simulation. Beams with a momentum acceptance of 5% should be used with caution for therapeutic applications to avoid extra dose to normal tissues beyond the tumour when the dose distal fall-off is located beyond the treatment volume.

Time-of-flight (TOF) is now a standard technology for positron emission tomography (PET), but its effective use for small diameter PET systems has not been studied well. In this paper, we simulated a brain-dedicated TOF-PET system with a hemispherical detector arrangement. We modeled a Hamamatsu TOF-PET module (C13500-4075LC-12) with 280 ps coincidence resolving time (CRT), in which a 12 x 12 array of multi pixel photon counters (MPPCs) is connected to a lutetium fine silicate (LFS) crystal array of 4.1 x 4.1 mm2 cross section each, based on one-to-one coupling. On the other hand, spatial resolution degradation due to the parallax error should be carefully addressed for the small diameter PET systems. The ideal PET detector would have both depth-of-interaction (DOI) and TOF capabilities, but typical DOI detectors that are based on light sharing tend to degrade TOF performance. Therefore, in this work, we investigated non-DOI detectors with an appropriate crystal length, which was a compromise between suppressed parallax error and decreased sensitivity. Using GEANT4, we compared two TOF detectors, a 20 mm long non-DOI and a 10 mm long non-DOI, with a non-TOF, 4-layer DOI detector with a total length of 20 mm (i.e., 5 x 4 mm). We simulated a contrast phantom and evaluated the relationship between the contrast recovery coefficient (CRC) and the noise level (the coefficient of variation, COV) for reconstructed images. The 10 mm long non-DOI, which reduces the parallax error at the cost of sensitivity loss, showed better imaging quality than the 20 mm long non-DOI. For example, the CRC value of a 10 mm hot sphere at COV = 20% was 72% for the 10 mm long non-DOI, which was 1.2 times higher than that of the 20 mm long non-DOI. The converged CRC values for the 10 mm long non-DOI were almost equivalent to those of the non-TOF 4-layer DOI, and the 10 mm long non-DOI converged faster than the non-TOF 4-layer DOI did. Based on the simulation results, we evaluated a one-pair prototype system of the TOF-PET detectors with 10 mm crystal length, which yielded the CRT of 250 ± 8 ps. In summary, we demonstrated support for feasibility of the brain-dedicated TOF-PET system with the hemispherical detector arrangement.

Time-of-fligfrt (TOF) PET improves image quality and quantitative accuracy compared with a conventional PET system. While it is true that TOF works better for larger objects, recent improvement in timing resolution has encouraged application of TOF to brain-dedicated PET systems. Thus, as the second prototype of the helmet-type PET, we have developed a new TOF brain-dedicated PET prototype using detector modules of 12×12 lutetium fine silicate (LFS) crystals (4.1×4.1×10 mm3) connected to a 12×12 (4 mm pitch, 144-ch) MPPC array. In this paper, we investigated another detector module, which has the same outer size but smaller crystals: 16×16 LFS of 3.1×3.1×10 mm3 size coupled to 16×16 (3 mm pitch, 256-ch) MPPC array. The 3-mm 256-ch module showed an energy resolution of 12.0%. For the coincidence response function, the 3-mm module showed a better full width at half maximum (FWHM) of 1.9 mm compared with the 4-mm 144-ch module (2.4 mm). The FWHM was improved by 21%. The coincidence resolving time obtained by the 3-mm 256-ch module was 241 ps. The energy resolution and coincidence resolving time were almost the same between the two modules. The 3-mm 16x16 MPPC-based TOF-PET module can be expected to improve spatial resolution without compromising the energy resolution and coincidence resolving time compared with the 4-mm 12×12 module.

A small animal positron emission tomography (PET) scanner employs a scintillation crystal with a small cross section to improve the spatial resolution. However, the identification of crystals becomes more difficult as the cross section of the crystal is reduced. In particular, the identification of edge crystals is more difficult than the central crystals. The aim of this study is to optimize a light guide design of a small animal PET detector to improve the resolvability of the edge crystals using GATEv6.2 optical simulation. The small animal PET module consists of an 11 × 11 array of pixelated LYSO crystals (0.92×0.92×10.0 mm3), a 1 mm thick light guide, and a 4 × 4 array SiPM (Hamamatsu Photonics, Japan; S13361-3050NE-04; each channel has an effective area of 3 × 3 mm2). The optical characteristics of LYSO and the SiPM were taken into account for the GATEv6.2 optical simulation. In order to improve the crystal resolvability in the edge and corner regions, four air slits were inserted into the light guide. The flood map was obtained with various slit depths of 0.2, 0.5, and 0.8 mm, respectively. The identification of the corner crystals could be improved by using a combination of a light guide thickness of 1 mm, and a slit depth of 0.5 mm without compromising energy resolution. In future, the optical simulation results will be validated by an experimental measurement.

In carbon ion therapy, visualization of the range of incident particles in a patient body is important for treatment verification. In-beam positron emission tomography (PET) imaging in ion therapy is one of the method for verification of treatment due to the high quality of PET images. We have already shown the feasibility of radioactive beams of 15O and 11C using in-beam PET imaging using our OpenPET system. Recently, we have developed a whole gamma imaging (WGI) system which can work as PET, single gamma-ray and triple gamma-ray imaging simultaneously. The WGI system has high potential to detect location of 10C, which emits positron with a simultaneous gamma-ray of 718 keV, and activity of other produced positron emitting nuclei within patient body during ion therapy. In this work, we focus on investigation of performance of WGI system for 10C irradiation. First, the performance of scatterer detector of the WGI system regarding the radiation hardness was studied for 10C irradiation, then the performance of WGI was studied by simulation using the Geant4 code. The scatterer detector consisted of a segmented GAGG crystal and a multi-pixel photon counter (MPPC) and its performance was studied as a PMMA phantom was irradiated with 5 and 400 spills of 10C with energy of 350 MeV/u. No damage to the MPPC (scatterer detector) was observed even though after irradiation of 400 spills (~1.9×105 particle per spill). Sensitivity values of WGI system by simulation of a 10C nuclide at the center of field of view (FOV) for PET mode imaging, single gamma-ray of 718 keV imaging and triple gamma-ray imaging were 7.85%, 0.28% and 0.012% respectively. The performance of WGI system is going to be evaluated for 10C irradiation in the near future.

PET detectors with both time-of-flight (TOF) and depth-of-interaction (DOI) capabilities are ideal, but DOI-TOF PET detectors have not been studied well. In this paper, we develop a 4-layer DOI TOF detector. The key item is a recently commercialized module of multi pixel photon counters (MPPCs) (C13500 series, Hamamatsu Photonics K. K., Japan). The MPPC array is the through silicon via (TSV) type with an effective area of 6 x 6 mm3 (0.075 mm pitch sub pixels), which is arranged as an 8 x 8 array. At first, a pair of lutetium fine silicate (LFS) crystals each sized in 4 x 4 x 10 mm3 was placed on the center of each one MPPC channel. The CRT value was 252 ps. Afterward one of those detectors was used as the reference detector. Then cerium doped lutetium yttrium orthosilicate (LYSO) crystals sized in 2.8 x 2.8 x 5 mm3 were arranged in 8 x 8 x 4-layer based on our special reflector arrangement. The 4-layer LYSO array were coupled to the MPPC modules via a light guide. In the position map of the 4-layer LYSO crystal block, most of crystals could be identified. The averaged CRT value for crystals of the central part in the position map for the reference detector was 486 ± 106 ps. In timing spectrum of the third layer and the fourth layer, other components were observed. This was presumed to be due to contamination caused by incomplete crystal identification. Individual specificity for each MPPC channel was required to be calibrated for complete crystal identification. In conclusion, we developed a 4-layer DOI TOF detector and obtained around 500 ps averaged CRT value for the reference detector.

We developed a compact receiver optical subassembly (ROSA) for 100-Gigabit Ethernet (100 GbE) using multimode-output-arrayed waveguide grating (MM-AWG) and arrayed photodiodes (PDs). The four-channel silica-based MM-AWG has low insertion loss of less than 1 dB. The back-side-illumined PD with maximized-induced current structure provides high responsivity of 0.95 A/W. To avoid the distortion of the responsivity spectrum due to poor coupling between the multimode beam and PD, we employ a racetrack shape for the active region of the PD. The optical coupling between the MM-AWG and lens-coupled PD is optimized in terms of the flattening ratio of the racetrack shape. The fabricated ROSA has high responsivity of over 0.7 A/W with a flat-top spectrum and obtains high environmental stability thank to its large assembly tolerance of over ± 4 μm. For 4 × 25−Gb/s signals after 10-km transmission, the minimum receiver sensitivity of the ROSA has a margin of 4.8 dB for the Ethernet standard. The transmission performance with a 100-GbE transmitter optical subassembly was also confirmed.

Digital coherent transmission systems with multilevel and multicarrier modulation formats have been moving beyond 100-G systems. In this paper, we report a one-chip 400-G coherent receiver founded on a silica-based planar lightwave circuit (PLC) integration platform. To integrate a polarization beam splitter (PBS), two polarization rotators, four-optical hybrids, and 16 high-speed photodiodes (PDs) in one chip, we employed a 5%-Δ waveguide with a minimum bending radius of 300 μm, and the heterogeneous integration of InP-PDs. To achieve a compact receiver without any degradation in optical passive performance, we also investigated a three-branched spot size converter with a low loss and a high-fabrication tolerance and a waveplate type PBS with a high-polarization extinction ratio. Using these techniques, we fabricated a dual-carrier dual-polarization (DP) 16-level quadrature amplitude modulation (QAM) receiver PLC, and successfully demonstrated 32-Gbaud DP-16QAM signal demodulation for each channel.

We are developing a compact and high-sensitivity brain-dedicated PET scanner, which consists of a hemispherically arranged detector unit and an add-on detector unit. Following our first idea of using a chin position as the location of the add-on detector (helmet-chin PET), a neck position has been selected as the location (helmet-neck PET). We have developed prototypes of both geometries using the 4-layered depth-ofinteraction (DOI) detector (2.8 mm sized GSOZ scintillators and a 64 ch PMT) which does not have time-of-flight (TOF) capability. On the other hand, a new TOF-PET detector module which consists of 4.1 mm sized LFS scintillators and multi pixel photon counters (MPPCs) is now commercially available (C135004075LC-12, Hamamatsu Photonics K.K.). Using one-to-one crystal-photodetector coupling, it is possible to achieve a 280 ps coincidence resolving time (CRT), although the Anger-type calculation, which is essential for the 4-layered DOI detector, cannot be applied. In this paper, therefore, we investigated the suitability of this TOF-PET detector module for the next helmetneck PET. At first, the helmet-neck PET with 20 mm crystal length, which is a standard parameter of the module, was modeled by GEANT4, and performance results were compared with those of the current helmet-neck PET prototype. We observed a compromised image quality; the non-DOI capability counteracted the TOF gain. On the other hand, the helmet-neck PET with shortened crystal length (10 mm) outperformed the current helmet-neck PET prototype; the shortened crystal length reduced the parallax error, and TOF information compensated for the loss of sensitivity. Based on the GEANT4 simulation results, we fabricated a one-pair prototype of the TOF-PET module with 10 mm length, which yielded 11.6 % energy resolution at 511 keV and 281.8\pm 9.6 ps CRT at FWHM. In conclusion, we confirmed suitability of the 280 ps-CRT non-DOI detector for the next helmet-neck PET.

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.

The bone-bonding ability of a material is evaluated by examining apatite formation on its surface in simulated body fluid (SBF). Partially stabilized zirconia (ZrO2) is currently attractive as an alternative to titanium (Ti) implants; however, no quantitative analysis of apatite formation between Ti and ZrO2 in SBF has been reported. In the present study, we quantitatively evaluated apatite formation onto Ti or ZrO2 in SBF using the 27 MHz quartz crystal microbalance method (QCM). In the QCM measurements, apatite formation was detected as a frequency decrease in the Ti or ZrO2 sensor. Frequency decreases were observed at around 1 hour for Ti and at around 2 hours for the ZrO2 sensor after the injection of SBF. This revealed that the Ti sensor showed faster apatite formation than ZrO2. There was no significant difference in the amounts of apatite formation between the Ti and ZrO2 sensors after 24 hours of apatite formation in SBF. In conclusion, the present quantitative study using QCM revealed that apatite formation on the Ti surface in the SBF was obviously faster than that on the ZrO2 surface. Faster apatite formation may predict faster initiation of bone formation on Ti compared with ZrO2.

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.

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.

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 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.

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.

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.

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 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.

It is postulated that biofilm formation in the oral cavity causes some oral diseases. Lactoferrin is an antibacterial protein in saliva and an important defense factor against biofilm development. We analyzed the adsorbed amount of lactoferrin and the dissociation constant (Kd) of lactoferrin to the surface of different dental materials using an equilibrium analysis technique in a 27 MHz quartz crystal microbalance (QCM) measurement. Four different materials, titanium (Ti), stainless steel (SUS), zirconia (ZrO2) and polymethyl methacrylate (PMMA), were evaluated. These materials were coated onto QCM sensors and the surfaces characterized by atomic force microscopic observation, measurements of surface roughness, contact angles of water, and zeta potential. QCM measurements revealed that Ti and SUS showed a greater amount of lactoferrin adsorption than ZrO2and PMMA. Surface roughness and zeta potential influenced the lactoferrin adsorption. On the contrary, theKdvalue analysis indicated that the adsorbed lactoferrin bound less tightly to the Ti and SUS surfaces than to the ZrO2and PMMA surfaces. The hydrophobic interaction between lactoferrin and ZrO2and PMMA is presumed to participate in better binding of lactoferrin to ZrO2and PMMA surfaces. It was revealed that lactoferrin adsorption behavior was influenced by the characteristics of the material surface.

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.

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.

In particle therapy, in-beam positron emission tomography (PET) is expected to enable in situ noninvasive confirmation of the treatment delivery. For accurate range and dose verification or three-dimensional (3D) volume imaging, however, correction of the biological washout effect in a living body is necessary. In this study, we measured the washout rate in a rabbit brain using the recently developed technology for oxygen beam radiation as well as carbon ion beam radiation. To measure components of washout, three radionuclides, 10C, 11C and 15O, which were generated as secondary beams in the Heavy Ion Medical Accelerator in Chiba (HIMAC), were irradiated on the rabbit brain under two conditions, live and dead. In-beam data were acquired by our whole body dual-ring OpenPET, which enables 3D in-beam imaging. Regions of interests (ROIs) were set as a 3D positron distribution and the time activity curves (TACs) of the irradiated field were acquired. We obtained the washout rate for those conditions based on multiple component model analysis. A difference between washout speed in 11C ions and the 15O ions was observed. The observed medium and slow biological decay rates of 11C ions in rabbit brain were 0.30 min−1 and 0.004 min−1, respectively. Those values were consistent with the previous rabbit study results acquired by other imaging modalities, such as the pair of positron cameras or our single-ring small animal OpenPET prototype. The observed medium and slow biological decay rates of 15O ions were 0.72 min−1 and 0.024 min−1, respectively, which were faster than those of the 11C ion. Also, the medium biological decay rate of 15O ions was close to the washout rate in cerebral blood flow (CBF) measurements by dynamic PET with 15O-labeled water. These results should help to establish an accurate washout correction model.

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 mm3 and 1.5 × 1.5 × 20 mm3 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 mm3 with 7 DOI segments and an 8 × 8 crystal array of 1.5 × 1.5 × 20 mm3 with 13 DOI segments. Each readout included a 4 × 4 channel of the 3 × 3 mm2 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.

Objectives All-in-one adhesive systems have been recently developed to simplify bonding procedures. The adhesives containing acidic resin monomers generate a relatively thin bonding zone between dentin and composite. This zone may be left acidic and permeable when polymerization is poor. In this study, the effect of water contained in dentin on the quality of the bonding interface was morphologically investigated for all-in-one adhesives. Methods Intact coronal dentin (hydrated dentin), desiccated coronal dentin (dehydrated dentin), caries-affected dentin (CAD) and resin composites were used for adherends to assess the effects of water contained in dentin on the ultra-structures of bonding interfaces created with two all-in-one adhesives and a resin composite. Results The bonding interfaces were observed under TEM without demineralization. Voids of various sizes were found at the bottom of the adhesive resin layers along the bonding interface of hydrated dentin, while dehydrated dentin, CAD and resin composites did not generate voids. The results showed that the voids were possibly formed by water that had penetrated from the underlying dentin. Conclusion When the adherend contains little water, the formation of voids will not occur. It was verified that a phenomenon of void formation would not occur in a clinical situation in which caries-affected dentin is mainly subjected to adhesive practices.

Dedicated brain PET scanner becomes an important tool for early diagnosis of Alzheimer's disease and brain function studies. The spatial resolution of the PET system can be improved by use of advanced depth-of-interaction (DOI) detectors, and its sensitivity can be enhanced by increasing its solid angle. Conventionally, PET scanners are designed based on a cylindrical geometry, and the sensitivity is limited due to the small solid-angle coverage. On the other hand, we have proposed a dedicated brain PET scanner based on a hemispheric-shaped and a chin detector (here after referred to as helmet-chin PET). The chin detector helps to increase the number of possible lines-of-response in the hemisphere. In this study, we evaluate the sensitivity of the helmet-chin PET under a realistic scanner design using Geant4 simulation toolkit. The scanner was constructed from 54 four-layer DOI block detectors arranged in a hemisphere (helmet part) of radius 126.5 mm and a chin detector. The helmet part had three rings with different radii and number of block detectors, and a top cover with 5 block detectors arranged in a cross-shaped geometry. Each block detector consisted of 16 × 16 × 4 array of GSO crystals with a dimension of 2.8 × 2.8 × 7.5 mm3. The sensitivity of the helmet-chin PET was compared to that of a cylindrical PET constructed from the same number and type of block detectors. The point source sensitivity of the helmet-chin PET was 1.4 times higher around the bottom part of the helmet and 4 times higher at the top part of the helmet compared to that of the cylindrical PET. The results showed that the helmet-chin PET can significantly improve sensitivity at the cerebellum and cerebrum regions, and could be promising for early diagnosis of Alzheimer's disease and accurate brain function studies. Recently, we have developed the first helmet-chin PET prototype.

We are developing a high-performance brain PET scanner, jPET-D4, which provides 4-layer depth-of-interaction (DOI) information. The scanner is designed to achieve not only high spatial resolution but also high scanner sensitivity with the DOI information obtained from multi-layered thin crystals. The scanner has 5 rings of 24 detector blocks each, and each block consists of 1024 GSO crystals of 2.9 mm/spl times/2.9 mm/spl times/7.5 mm, which are arranged in 4 layers of 16/spl times/16 arrays. At this stage, a pair of detector blocks and a coincidence circuit have been assembled into an experimental prototype gantry. In this paper, as a preliminary experiment, we investigated the performance of the jPET-D4's spatial resolution using the prototype system. First, spatial resolution was measured from a filtered backprojection reconstructed image. To avoid systematic error and reduce computational cost in image reconstruction, we applied the DOI compression (DOIC) method followed by maximum likelihood expectation maximization that we had previously proposed. Trade-off characteristics between background noise and resolution were investigated because improved spatial resolution is possible only when enhanced noise is avoided. Experimental results showed that the jPET-D4 achieves better than 3 mm spatial resolution over the field-of-view.

Advanced input/output (I/O) technology is reported for leading-edge system on a chip (SoC) applications, including high-speed I/O and RF circuits. Our device having a laterally modulated channel shows sufficient reliability even at 3.3 V operation with the same size as a conventional 2.5 V device. Since this technology also improves current drivability, the layout area of an I/O circuit block can be reduced down to 55% because of a reduced total gate width. Moreover, a metal-on-gate (MOG) option has been developed for RF applications, and an fmax of 55 GHz was achieved.

It has been reported that the adhesive resin layer of all-in-one adhesives is permeable and allows the formation of a water channel or water tree. The effects of a smear layer on the ultra-structure of bonding interface created with three all-in-one adhesives and a resin composite were evaluated in this study. Dentin surface was ground with of 180-, 600-, or 2000-grit SiC paper to produce different smear layer thickness. The bonding interfaces were observed under a transmission electron microscope without demineralization. Voids of various sizes and water channels were found at the bottom of the adhesive resin layer along the bonding interface of SiC 180-grit dentin, while SiC 2000-grit dentin did not produce any voids. The results showed that the voids were possibly related to water that had penetrated from the underlying dentin. A smear layer may have an adverse influence on the bonding performance of all-in-one adhesives to dentin.

Self-etching primer adhesives have recently been introduced to simplify bonding. However, the fundamental bonding mechanism of self-etching primers to enamel is not yet fully understood. This study aimed to investigate resin-enamel bonds of self-etching primer adhesives on ground enamel. Two self-etching primer adhesives (Clearfil Liner Bond 2 V and Clearfil SE Bond) were used in this study. A total-etch adhesive (One-Step) was used as a control. Resin-enamel beams were subjected to the microtensile bond test. Subsequently, the failure modes of all specimens were quantified using image analysis. Undemineralized and demineralized ultrathin sections of the resin-enamel bonded specimens were examined using transmission electron microscopy. The bond strengths of Clearfil SE Bond (39.8 +/- 11.9 MPa) and One-Step (46.2 +/- 12.7 MPa) were significantly greater than that of Clearfil Liner Bond 2V (30.4 +/- 6.2 MPa). Scanning electron microscopy of the fractured surfaces revealed the failure direction and weakest portion within each bond. Transmission electron microscopy showed a thin hybridized complex of resin in enamel produced by the self-etching primers without the usual micrometer-sized resin tags seen in resin-enamel bonds produced using the total-etch adhesive. The morphological features of the resin-enamel bonds produced by two self-etching primers tested were different from that created with the total-etch adhesive.