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Recently, silicon photomultipliers (SiPMs) have become established as photo-sensors for PET scanners. Commercially available SiPM arrays are typically about 3–4 cm in size. In order to develop larger detectors with an Anger calculation, multiple SiPM arrays need to be combined. This configuration requires the use of a light guide and has inactive areas between SiPM arrays. If not addressed, crystal identification degrades not only for peripheral crystals but also for crystals to bridge the gap between the SiPM arrays. On the other hand, we have developed the crosshair light-sharing (CLS) PET detector, which is based on a single-ended readout scheme with roughly quadrisected crystals comparable in size to a SiPM, with depth-of-interaction (DOI) capability. The CLS PET detector based on the local centroid calculation was expected to mitigate the edge effect similar to what the one-to-one coupling detector is able to do. In this work, we developed the axially long CLS PET detector with two multipixel photon counter (MPPC) arrays. The proposed long CLS PET detector consisted of 30 × 14 gadolinium fine aluminum garnet (GFAG) arrays coupled to two 8 × 8 MPPC arrays without the light guide. From 511-keV uniform irradiation, responses of all crystal elements could be separated clearly on a 2D position histogram after applying the Anger calculation. Pulse heights of additional crystals to bridge the gap were 18% lower than those of crystals at the center of the MPPC array, but similar to that of the peripheral crystals based on non-uniformity of the MPPC array. On the other hand, energy resolutions of additional crystals to bridge the gap were almost the same to those of other crystals. The long CLS PET detector promises improvement of the packing fraction while keeping performance.

[Objectives] A PET system can be more efficient in terms of size and cost when it is designed as an organ-dedicated or application-specific system. Considering the potential need for brain PET, we proposed the concept of a hemispherical detector arrangement, which enables higher sensitivity with fewer number of detectors than a conventional cylindrical geometry has. A laboratory benchtop prototype has been evolved into a complete brain PET system, which has been commercialized in Japan under the product name of VrainTM. In this work, we characterize the system and carry out its first human imaging tests. [Methods] The VrainTM has 54 detectors. A hemispherical part is formed by 45 detectors and the other 9 detectors are located at the backside of the neck. Each detector is a one-to-one combination of lutetium-based scintillators (crystal element size: 4.1×4.1×10 mm3) and silicon photomultipliers (SiPMs) (active area size: 4×4 mm2). The inner diameter of the bottom detector ring is 279 mm. The crystal thickness is optimized by simulation to reduce the parallax error and to improve the TOF performance. The energy window is also optimized to 450–590 keV to get better image quality. We evaluated the physical performance of the VrainTM according to the NEMA NU 2-2018 standards. Some measurements were added and others were modified to suit the hemispherical detector arrangement. Finally, we carried out the first healthy volunteer imaging. 18F-FDG of 3.7 MBq/kg was intravenously injected to a male subject (42 years old). The PET measurement duration was 10 min starting at 45 min after injection. PET images were reconstructed using the OSEM with 4 iterations and 8 subsets. A Gaussian filter of 4 mm FWHM was applied to PET images. CT images, which were obtained by another PET/CT scanner, were used for attenuation and scatter corrections. [Results] The 2.2 mm rods of a small rod phantom were resolved. The TOF resolution at the peak noise-equivalent count ratio (NECR) (9.8 kBq, SNMMI 2022 Annual Meeting

Using time-of-flight (TOF) information in image reconstruction improves image signal-to-noise ratio and quantitative accuracy in positron emission tomography (PET). A new TOF-PET detector module with a 3.2 mm pitch lutetium fine silicate (LFS) scintillator array one-to-one coupled to a 16×16 (256-ch) silicon photomultiplier (SiPM) array was made commercially available (C13500 series, Hamamatsu Photonics K.K.). In this study, as a candidate detector module for the next generation brain-dedicated PET, we changed the scintillator length of 20 mm to 10 mm according to our helmet-type PET geometry and investigated the basic performance of the PET detector module, including its energy resolution, sensitivity, coincidence response function (CRF) and coincidence timing resolution (CTR). All performance values were compared with those of the 4.2 mm pitch 144-ch detector module which was selected for our current helmet-type PET prototype. The energy resolution was 12% at 511 keV. The sensitivity was about 10% lower compared with those of the 4.2 mm pitch module. The average full width at half maximum (FWHM) of the CRFs was 1.9 mm. The CTRs had values of 235–241 ps with various energy windows after applying timing calibration. The CTR was not significantly changed (<10 ps) at the single count rate of 412 kcps or lower.

Myocardial perfusion imaging (MPI) with PET plays a vital role in the management of coronary artery disease. High sensitivity systems can contribute to maximizing the potential value of PET MPI; therefore, we have proposed two novel detector arrangements, an elliptical geometry and a D-shape geometry, that are more sensitive and more compact than a conventional large-bore cylindrical geometry. Here we investigate two items: the benefits of the proposed geometries for cardiac imaging; and the effects of scatter components on cardiac PET image quality. Using the Geant4 toolkit, we modeled four time-of-flight (TOF) PET systems: an 80-cm-diameter cylinder, a 40-cm-diameter cylinder, a compact ellipse, and a compact D-shape. Spatial resolution and sensitivity were measured using point sources. Noise equivalent count rate (NECR) and image quality were examined using an anthropomorphic digital chest phantom. The proposed geometries showed higher sensitivity and better count rate characteristics with a fewer number of detectors than the conventional large-bore cylindrical geometry. In addition, we found that the increased intensity of the scatter components was a big factor affecting the contrast in defect regions for such a compact geometry. It is important to address the issue of the increased intensity of the scatter components to develop a high-performance compact cardiac TOF PET system.

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 multipixel 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.

[Objectives] 18F-FDG PET is useful for diagnosis of breast cancer. Compared to whole-body imaging, local breast imaging with a dedicated PET system can more clearly visualize the extent of the primary breast tumor and axillary lymph nodes metastasis. Breast-dedicated PET systems are categorized into two geometries: a ring-shaped detector arrangement and a dual flat-panel detector arrangement. Although the flat-panel system allows imaging axillary lymph nodes from a similar view as X-ray mammography, PET images are blurred (i.e. spatial resolution is degraded) in the direction perpendicular to the detectors due to the limited angular coverage. To compensate for this issue, we proposed a dual round-edge detector arrangement, in which the detector blocks at both edge positions were tilted toward the center of the field-of-view (FOV). The proposed detector arrangement is expected to reduce image blurring and improve spatial resolution while keeping the advantages of the dual panel arrangement. For a proof of concept, we developed a small prototype and evaluated the spatial resolution. [Methods] We used the crosshair light-sharing (CLS) detectors which had depth-of-interaction (DOI) and time-of-flight (TOF) measurement capabilities*. A 14×14 array of 1.45×1.45×15 mm3 GFAG scintillator was coupled with an 8×8 array of silicon photomultipliers (SiPMs) each with a photosensitive area of 3.0×3.0 mm2. DOI was digitalized into three bins. The data acquisition system was the TOFPET2 ASIC (PETsys Electronics), which was designed to digitize energy and time signals from photo sensors. The small prototype was composed of 32 detector blocks. We examined the conventional flat-panel arrangement and our proposed round-edge arrangement. A 22Na Derenzo-like multi-rod phantom (rod diameters: 1.6, 2.2, 3.0, 4.0, 5.0 and 6.0 mm) was used for spatial resolution measurement. The phantom was measured (90 min) in the two directions (coronal and axial planes) at the center of the FOV. [Results], SNMMI 2021 Annual Meeting

Once a high-resolution PET detector with both depth-of-interaction and time-of-flight capabilities is established, it will be applied to various-type PET systems using a software-based coincidence method. Toward this goal, we have developed a crosshair light-sharing (CLS) detector. In this work, as the first development of a practical system based on the CLS detector, we realized a high-resolution portable small animal PET with a long axial field-of-view (FOV) of 20 cm. The system was composed of 128 CLS detectors. All devices were mounted on a pushcart, and the system was operated on a 100V power supply. The axial FOV was 207 mm, which covered the total-body of a rat. A 22Na ultra-micro hot phantom was used for spatial resolution measurement, and the NEMA NU4 image quality phantom was used for image quality test. The developed CLS-PET system successfully resolved 0.75 mm rods. Subsequently, normal mouse and rat imaging with 18F-NaF and 18F-FDG were demonstrated. For the NaF-PET, mouse and rat total-body images were obtained, and detailed bone structures were clearly imaged. For the mouse FDG-PET, cardiac FDG uptakes were clearly visualized by the CLS-PET system. In conclusion, the CLS-PET system achieved <1 mm spatial resolution and successfully provided mouse and rat total-body images., 2021 IEEE NSS/MIC

Roots are essential to plants for uptake of water and nutrients. For the improvement of crop production, it is necessary to understand the elucidation of the root development and its function under the ground. Espeially, photosynthate translocation from plant leaves to roots is an important physiological function that affects the root elongation, adaptation to the soil environment and nutrients uptake. To evaluate the translocation dynamics to roots, positron emission tomography (PET) and 11C tracer have been used. However, the spatial resolution is degraded at roots that develop around the peripheral area of field of view (FOV) due to parallax errors. In this study, to overcome this problem, we developed a small OpenPET prototype applying four-layer depth-of-interaction detectors. We demonstrated the imaging capability of 11C-photosynthate translocation to rice roots that develop throughout the entire PET field. We also tried to obtain structural information of roots by high-throughput X-ray computed tomography (CT) system using the same test plant. As a result, we succeeded in visualizing the root structure that developed around the peripheral region of FOV and imaging the accumulation of 11C-photosynthate to the roots in those areas without degrading the spatial resolution. From obtained images, we also succeeded in evaluating the translocation dynamics varied by roots. The combined use of the high-throughput CT system and the OpenPET prototype was demonstrated to be appropriate for structural and functional analysis of roots.

In pancreatic cancer surgery, accurate identification and resection of intrapancreatic residual tumors are quite difficult. We have developed a novel open-typed PET system (called 'OpenPET'), which enables high-resolution PET-guided surgery in real time, and demonstrated that OpenPET-guided surgery with intraperitoneally administered 64Cu-labeled anti-epidermal growth factor receptor antibody cetuximab is useful to detect and resect primary pancreatic cancer. Here, we investigated applicability of OpenPET-guided surgery for unexpected residual intrapancreatic tumors and examined its survival benefit over conventional surgery.

Silicon photomultiplier (SiPM) based scintillation detectors are widely used for positron emission tomography (PET), but their application to Compton cameras should be further explored. Whole gamma imaging (WGI) is a combination of PET and a Compton camera realized by inserting a scatter detector ring into a PET ring. In a previous study, we developed a WGI prototype in which the scatter detector consists of Gd3Al2Ga3O12:Ce (GAGG) scintillators coupled with SiPM for a proof-of-concept. However, its Compton imaging performance was not as good as its PET imaging performance. In this paper, we developed a two-layer staggered GAGG scatter detector which was optimized for WGI. GAGG crystals 1.45×1.45×4.5 mm3 in size were arranged into a 13×13 array for the 1st layer and a 14×14 array for the 2nd layer with a staggered arrangement. The two-layer crystal block was optically coupled to an 8×8 SiPM array (3 mm pixel). Using radioactive sources with different energies, we investigated the energy resolution performance experimentally. Almost all crystals were clearly separated in the flood histogram at multiple energies. The developed detector showed energy resolutions of 7.7% to 8.5% at 511 keV, which was better than that of the detector of the current WGI prototype. The next generation WGI system was modeled in simulations using the obtained energy resolution data. The simulation results showed that the WGI with the developed detector had 1.2 times better sensitivity and better angular resolution in the peripheral region than the current WGI prototype.

We developed a whole gamma imaging (WGI) prototype composed of a scatterer ring insert and an absorber ring. It was the world’s first realization of a full-ring Compton camera geometry. In this study, we focused on the data sufficiency condition (DSC) for Compton image reconstruction. Contrary to PET which requires a full-ring geometry to satisfy the DSC, Compton imaging does not require a full ring theoretically. Reducing the detector-ring coverages can improve flexibility of the geometry design and reduce manufacturing costs although sensitivity is decreased. However, the DSC for reconstruction is not guaranteed in a practical situation due to actual absorber ring arrangement and detection limits in scattering angle. In this study, we experimentally assessed the DSC for the angular coverages. We evaluated image artifacts on reconstructed Compton images because, in general, images distort and exhibit artifacts when the DSC is not satisfied, degrading quantitative accuracy. We measured a cylindrical phantom filled with 89Zr solution of 10.2 MBq by the WGI prototype for 60 min and extracted 909-keV Compton events. We selected events related to the detector blocks marked as available to change detector angular coverages defined for the phantom bottom point. First, we changed the number of detectors in the scatterer ring, keeping the full-ring absorber. Next, we changed the absorber ring angular coverage by changing the number of detectors, keeping the scatterer ring at the number where the angular coverage just exceeded 180°. As a result, when the angular coverage of the scatterer detector was less than 180°, reconstructed images exhibited artifacts. The absorber ring detector with less than 180° coverage showed artifacts when used with the scatterer detector with more than 180° coverage. We concluded that angular coverages of more than 180° for both the scatterer and absorber detectors against any region on a subject are the DSC for Compton image reconstruction., IEEE NSS MIC 2021

Breast-dedicated PET systems are categorized into two geometries: a ring-shaped detector arrangement and a dual flat-panel (FP) detector arrangement. Although there are some advantages in the FP arrangement, PET images are blurred due to the limited angular coverage. To compensate for this issue, we have proposed a dual round-edge (RE) detector arrangement, in which detectors at both edge positions are tilted toward the center of the field-of-view. In this study, for a proof-of-concept of the RE arrangement, we developed the first bench-top prototype. Our original crosshair light-sharing (CLS) depth-of-interaction (DOI) detector was used; it consisted of a 14×14 array of 1.45×1.45×15 mm3 GFAG scintillator crystals coupled with an 8×8 array of silicon photomultipliers each with a photosensitive area of 3.0×3.0 mm2. The data acquisition system was the TOFPET2 ASIC (PETsys Electronics). We examined the conventional FP arrangement and the proposed RE arrangement using 32 CLS detectors. A 22Na point source and a multi-rod phantom (rod diameters: 1.6, 2.2, 3.0, 4.0, 5.0 and 6.0 mm) were used for spatial resolution measurements. The RE arrangement showed better spatial resolution compared with the FP arrangement (64% improvement in the vertical direction). For the multi-rod phantom, in the coronal plane (parallel to the detector surface), the 1.6 mm rods were clearly resolved in both arrangements. However, in the axial plane (perpendicular to the detector surface), the RE arrangement resolved the 2.2 mm rods that had not been resolved by the FP arrangement. We demonstrated that the proposed RE detector arrangement showed better spatial resolution than the conventional FP arrangement., 2021 IEEE NSS/MIC

Objective. Time-of-flight (TOF) and depth-of-interaction (DOI) are well recognized as important information to improve PET image quality. Since such information types are not correlated, many TOF-DOI detectors have been developed but there are only a few reports of high-resolution detectors (e.g. 1.5 mm resolution) for brain PET systems. Based on the DOI detector, which enables single-ended readout by optically coupling a pair of crystals and having a loop structure, we have developed the crosshair light sharing (CLS) PET detector that optically couples the four-loop structure, consisting of quadrisected crystals comparable in size to a photo-sensor, to four photo-sensors in close proximity arranged in a windmill shape. Even as a high-resolution detector, the CLS PET detector could obtain both TOF and DOI information. The coincidence resolving time (CRT) of the CLS PET detector needs to be further improved, however, for application to the brain PET system. Recently, a fast LGSO crystal was developed which has advantages in detection efficiency and CRT compared to the GFAG crystal. In this work, we developed the CLS PET detector using the fast LGSO crystal for the TOF-DOI brain PET system. Approach. The crystals were each 1.45 × 1.45 × 15 mm3 and all surfaces were chemically etched. The CLS PET detector consisted of a 14 × 14 crystal array optically coupled to an 8 × 8 MPPC array. Main results. The fast LGSO array provided 10.1% energy resolution at 511 keV, 4.7 mm DOI resolution at 662 keV, and 293 ps CRT with the energy window of 440–620 keV. Significance. The developed CLS PET detector has 290% higher coincidence sensitivity, 30% better energy resolution, and 32% better time resolution compared to our previous CLS PET detector.

Compton imaging or Compton camera imaging has been studied well, but its advantages in nuclear medicine and molecular imaging have not been demonstrated yet. Therefore, the aim of this work was to compare Compton imaging with positron emission tomography (PET) by using the same imaging platform of whole gamma imaging (WGI). WGI is a concept that combines PET with Compton imaging by inserting a scatterer ring into a PET ring. This concept utilizes diverse types of gamma rays for 3D tomographic imaging. In this paper, we remodeled our previous WGI prototype for small animal imaging, and we developed an image reconstruction method based on a list-mode ordered subset expectation maximization algorithm incorporating detector response function modeling, random correction and normalization (sensitivity correction) for either PET and Compton imaging. To the best of our knowledge, this is the world's first realization of a full-ring Compton imaging system. We selected 89Zr as an imaging target because a 89Zr nuclide emits a 909 keV single-gamma ray as well as a positron, and we can directly compare Compton imaging of 909 keV photons with PET, a well-established modality. We measured a cylindrical phantom and a small rod phantom filled with 89Zr solutions of 10.3 MBq and 10.2 MBq activity, respectively, for 1 h each. The uniform radioactivity distribution of the cylindrical phantom was reconstructed with normalization in both PET and Compton imaging. Coefficients of variation for region-of-interest values were 4.2% for Compton imaging and 3.3% for PET; the difference might be explained by the difference in the detected count number. The small rod phantom experiment showed that the WGI Compton imaging had spatial resolution better than 3.0 mm at the peripheral region although the center region had lower resolution. PET resolved 2.2 mm rods clearly at any location. We measured a mouse for 1 h, 1 d after injection of 9.8 MBq 89Zr oxalate. The 89Zr assimilated in the mouse bony s

We developed a human-scale single-ring OpenPET (SROP) system, which had an open space allowing us access to the subject during measurement. The SROP system consisted of 160 4-layer depth-of-interaction detectors. The open space with the axial width of 430 mm was achieved with the ring axial width of 214 mm and the ring inner diameter of 660 mm. The detectors were axially shifted to each other so that the detector ring was aligned along a plane horizontally tilted by 45∘ against the axial direction. The system was developed as a mobile scanner to be used not only in clinical PET rooms but also in charged-particle therapy treatment rooms as well as animal experiment rooms. Almost uniform spatial resolution better than 3 mm throughout the entire FOV was realized with an iterative image reconstruction method. Peak absolute sensitivity was 3.1%, and there was a region with sensitivity better than 0.8% for a length of more than 700 mm. An in-beam imaging experiment conducted at the HIMAC showed that the system was operable even at the highest beam intensity available for heavy-ion therapy. In addition, we conducted entire-body monkey dynamic imaging utilizing the long region inside the gantry by positioning a monkey along the direction having the longest FOV tilted by 45∘ against the axial direction. We concluded the developed system realizes versatile PET applications because of its wide-open space and mobility as well as high spatial resolution with sufficiently good sensitivity.

An error was introduced during the production of this article. In the published paper, figures 9 and 10 display extra axes which should not be there. The following are the corrected figures.

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.

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

To improve positron emission tomography (PET) image quality, depth-of-interaction (DOI) information and timeof-flight (TOF) information are key technologies. In this work, we developed the DOI-TOF detector based on our original singleended readout scheme with the continuous layered gadolinium fine aluminum garnet (GFAG) array. The size of each GFAG crystal is 1.45×1.45×20 mm3. The multi-pixel photon counter (MPPC) used as a photo-sensor has a surface area of 3.0×3.0 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.