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X-ray and gamma-ray photons are widely used for imaging but require a mathematical reconstruction step, known as tomography, to produce cross-sectional images from the measured data. Theoretically, the back-to-back annihilation photons produced by positron-electron annihilation can be directly localized in three-dimensional space using time-of-flight information without tomographic reconstruction. However, this has not yet been demonstrated due to the insufficient timing performance of available radiation detectors. Here, we develop techniques based on detecting prompt Cerenkov photons, which when combined with a convolutional neural network for timing estimation resulted in an average timing precision of 32 picoseconds, corresponding to a spatial precision of 4.8 mm. We show this is sufficient to produce cross-sectional images of a positron-emitting radionuclide directly from the detected coincident annihilation photons, without using any tomographic reconstruction algorithm. The reconstruction-free imaging demonstrated here directly localizes positron emission, and frees the design of an imaging system from the geometric and sampling constraints that normally present for tomographic reconstruction.

Objective. The aim of this study is to evaluate the performance characteristics of a brain positron emission tomography (PET) scanner composed of four-layer independent read-out time-of-flight depth-of-interaction (TOF-DOI) detectors capable of first interaction position (FIP) detection, using Geant4 application for tomographic emission(GATE). This includes the spatial resolution, sensitivity, count rate capability, and reconstructed image quality. Approach. The proposed TOF-DOI PET detector comprises four layers of a 50 × 50 cerium-doped lutetium–yttrium oxyorthosilicate (LYSO:Ce) scintillator array with 1 mm pitch size, coupled to a 16 × 16 multi-pixel photon counter array with 3.0 mm × 3.0 mm photosensitive segments. Along the direction distant from the center field-of-view (FOV), the scintillator thickness of the four layers is 2.5, 3, 4, and 6 mm. The four layers were simulated with a 150 ps coincidence time resolution and the independent readout make the FIP detection capable. The spatial resolution and imaging performance were compared among the true-FIP, winner-takes-all (WTA) and front-layer FIP (FL-FIP) methods (FL-FIP selects the interaction position located on the front-most interaction layer in all the interaction layers). The National Electrical Manufacturers Association NU 2-2018 procedure was referred and modified to evaluate the performance of proposed scanner. Main results. In detector evaluation, the intrinsic spatial resolutions were 0.52 and 0.76 mm full width at half-maximum (FWHM) at 0° and 30° incident γ -rays in the first layer pair, respectively. The reconstructed spatial resolution by the filter backprojection (FBP) achieved sub-millimeter FWHM on average over the whole FOV. The maximum true count rate was 207.6 kcps at 15 kBq ml−1 and the noise equivalent count rate (NECR_2R) was 54.7 kcps at 6.0 kBq ml−1. Total sensitivity was 45.2 cps kBq−1 and 48.4 cps kBq−1 at the center and 10 cm off-center FOV, respectively. The TOF and DOI reconstructions significantly improved the image quality in the phantom studies. Moreover, the FL-FIP outperformed the conventional WTA method in terms of the spatial resolution and image quality. Significance. The proposed brain PET scanner could achieve sub-millimeter spatial resolution and high image quality with TOF and DOI reconstruction, which is meaningful to the clinical oncology research. Meanwhile, the comparison among the three positioning methods indicated that the FL-FIP decreased the image degradation caused by Compton scatter more than WTA. [ABSTRACT FROM AUTHOR]

A 256 channel flat panel position sensitive photomultiplier tube (256ch FP-PMT) was evaluated for application to a depth of interaction (DOI) PET detector composed of small crystal elements. The 256ch FP-PMT has 52 x 52 mm opening area with 89% useful area. Its 256 anodes are placed at a 3.04 mm interval. To estimate the FP-PMT performance, light spread functions of anodes at central and peripheral regions of a prototype 256ch FP-PMT were measured with a [Gd.sub.2]Si[O.sub.5] (GSO) crystal sized 1.42 x 1.42 x 4.5 mm. The crystal cross section area is about one quarter of one anode area of the FP-PMT. It was found that light spread functions of peripheral anodes were similar to the functions of central anodes and also the functions measured with a 2.9 x 2.9 x 7.5 mm GSO crystal which has almost the same dimensions of cross-section as the anode area. Transit time fluctuation among the 256ch FP-PMT anodes was estimated by measuring time resolutions of a LuYSi[O.sub.5] (LYSO) crystal at some central and peripheral positions. The LYSO crystal has the same dimensions as the smaller GSO crystal. Ba[F.sub.2] was used for a reference detector. The obtained distributions show about the same time resolution between the central and peripheral positions and the full width at half maximum is (366 [+ or -] 15) ps. The transit time fluctuation is [+ or -] 106 ps. Two-dimensional position histograms of a 32 x 32 GSO crystal array and two layers of 9 x 9 GSO crystal arrays are obtained by uniform gamma-ray irradiation. The crystal dimensions are 1.42 x 1.42 x 4.5 mm so that the 32 x 32 array covers all the useful area and indicates variation of crystal identification performance over the useful area. The 9 x 9 x 2 array is coupled to peripheral region. The resultant histograms confirm that a 256ch FP-PMT has enough capability for identifying crystals of this size even on the periphery and in DOI arrangement. Index Terms--Multi-anode photomultiplier tube (PMT), position sensitive detector, scintillation detector, small animal positron emission tomography (PET).

We are now planning to develop a positron emission tomograph dedicated to small animals, such as rats and mice, which meets the demand for higher sensitivity. For the positron emission tomography (PET), we newly designed a four-layer depth of interaction (DOI) detector, which is constructed of all the same crystal elements. In this DOI detector, appropriate insertion of the reflector controls the behavior of scintillation photons by inserting the reflectors between crystal elements so that the DOI information of four layers can be extracted from one two-dimensional (2-D) position histogram made by Anger-type calculation. As a preliminary experiment, we measured crystal identification performance of the DOI detector, which consists of four layers of a 16 x 16 crystal array using [Gd.sub.2]Si[O.sub.5] crystals with Ce concentration of 0.5 mol %. Each crystal is in dimensions of 1.42 mm x 1.42 mm x 4.5 mm. A crystal block is optically coupled to a 256-channel flat panel position sensitive photomultiplier tube whose opening area is 52.0 mm x 52.0 mm. We obtained sufficient positioning performance for this four-layer DOI detector on the 2-D position histogram. We concluded that it would be a promising device to realize a small animal PET scanner with high sensitivity and high resolution. Index Terms--Depth of interaction, positron emission tomography (PET), small animal study.

A 256ch flat panel position sensitive photomultiplier tube (FP-PMT) is a promising device for a PET detector because of its large opening area, 52 mm x 52 mm, and small dead space. The useful area of the 256ch FP-PMT is 89% to the opening area. The 256ch FP-PMT contains 16 x 16 matrix anodes with 3.04 mm intervals between them so that the 256ch FP-PMT affords optical coupling with a 16 x 16 array of scintillation crystals having 3 mm x 3 mm bottom area. Its 14.7 mm thickness will also ensure a compact volume and less weight for the PET apparatus. Using a prototype 256ch FP-PMT, we measured light spread function of a central anode and crystal identification ability with 2.9 mm x 2.9 mm x 7.5 mm [Gd.sub.2]Si[O.sub.5] (GSO) crystals. The full width at half maximum of the light spread function was found to be 4.6 mm. As regards positioning performance, the resultant positioning image map assures its capability for crystal identification in a 16 x 16 array of the GSO crystals. For the use of a 256ch FP-PMT having a large useful area, we made a new proposal for easier construction of an array with many crystal elements. The way utilizing multi-layer polymer mirrors, a reflector, properly processed by laser can be applied to other various shaped detectors. Index Terms--Multi-anode PMT, position sensitive detector, positron emission tomography (PET), scintillation detector.

As part of the next generation PET project, uniformity of full energy pulse height for all crystal elements was improved in the depth of interaction (DOI) detector constructed of three-dimensional crystal arrays. In our previous report, we found that the DOI detector constructed of four stages of a 2 x 2 [Gd.sub.2]Si[O.sub.5]:Ce (GSO) crystal array provides good crystal identification performance but poor uniformity of the energy pulse height distribution. The upper stage crystal elements which stay further from the photocathode of a PMT have a tendency to show lower energy pulse height. For example, the ratio of the full energy peak of the top stage crystal to the bottom stage one was about 0.3. We designed a new DOI detector improved in the uniformity. By optimizing crystal surface finishes, reflector configurations, and optical coupling between crystal elements, we got comparable energy pulse height from the upper stage crystals to the bottom stage crystals. Despite this change of detector conditions, good separation between each area corresponding to crystal elements is maintained on two-dimensional histograms obtained by Anger-type position calculation. The uniform full energy pulse height of every stage crystal allows a narrower dynamic range of the electrical circuits, and may give a great advantage in getting an accurate scatter correction. It also improves energy and timing resolution. Index Terms--Depth of interaction, nuclear medicine, positron emission tomography (PET), scintillation detector.

A new method for a four-stage depth of interaction (DOI) detector is proposed. The four-stage DOI detector is constructed with two kinds of [Gd.sub.2] Si[O.sub.5]: Ce (GSO) crystals doped with different amounts of Ce, 0.5 mol% and 1.5 mol%. The amount of Ce in GSO determines the scintillation decay time constant, and it is 60 ns for the 0.5 mol% GSO and 35 ns for 1.5 mol% GSO. This difference led to the introduction of pulse-shape discrimination, which would distinguish between two kinds of event data from respective GSOs and sort them into two groups. By independently applying Anger-type position arithmetic to the data of each group, two two-dimensional (2-D) histograms are obtained. The crystal of interaction can be identified on these histograms in which only 0.5 mol% or 1.5 mol% GSO crystal elements are expressed. To evaluate this method, we constructed the four-stage DOI detector by alternately stacking 1.5 mol% GSO crystal stages and 0.5 mol% stages. The result of a scanning measurement with a [sup.137]Cs gamma-ray beam proved that the DOI detector had enough accuracy in crystal identification. Index Terms--Depth of interaction, gadolinium orthosilicate, positron emission tomography (PET), pulse-shape discrimination.

This is an explanatory paper on Sun Il Kwon et al., Nat. Photon. 15: 914-918, 2021 and some parts of this manuscript are translated from the paper. Medical imaging modalities such as X-ray computed tomography, Magnetic resonance imaging, positron emission tomography (PET), and single photon emission computed tomography, require image reconstruction processes, consequently constraining them to form cylindrical shapes. However, among them, only PET can use additional information, so called time of flight, on an event-by-event basis. If coincidence time resolution (CTR) of PET detectors improved to 30 ps, which corresponds to spatial resolution of 4.5 mm, directly localizing electron-positron annihilation point is possible, allowing us to circumvent image reconstruction processes and free us from the geometric constraint. We call this concept direct positron emission imaging (dPEI). We have developed ultrafast radiation detectors by focusing on Cherenkov photon detection. Furthermore, the CTR of 32 ps being equivalent to 4.8 mm spatial resolution is achieved by combining deep learning-based signal processing with the detectors. In this article, we explain how we developed the detectors and demonstrated the first dPEI using different types of phantoms, how we will tackle limitations to be addressed to make the dPEI more practical, and how dPEI will emerge as an imaging modality in nuclear medicine.