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BACKGROUND: Monolithic or semi-monolithic detectors are attractive for positron emission tomography (PET) scanners with depth-of-interaction (DOI) capability. However, they often require complicated calibrations to determine the interaction positions of gamma photons. PURPOSE: We introduce a novel hybrid detector design that combines pixelated and semi-monolithic elements to achieve DOI capability while simplifying the calibrations for positioning. METHODS: A prototype detector with eight hybrid lutetium-yttrium oxyorthosilicate (LYSO) layers having dimensions of 25.8 × 12.9 × 15 mm3 was constructed. The energy-weighted and energy-squared weighted averages were used for estimating the x- (pixelated direction) and y-positions (non-pixelated direction). Pseudo-pixels were defined as discrete areas on the flood image based on the crystal look-up table (LUT). The intrinsic spatial resolutions in the pixelated and non-pixelated directions were measured. The ratio of the maximum to the sum of the multipixel photon counter (MPPC) signals was used to estimate the DOI positions. The coincidence timing resolution (CTR) was measured using the average and energy-weighted average of the earliest n time stamps. Two energy windows of 250-700 and 400-600 keV were applied for the measurements. RESULTS: The pattern of the flood images showed discrete event clusters, demonstrating that simple calibrations for determining the x- and y-positions of events could be achieved. Under 400-600 keV energy window, the average intrinsic spatial resolutions were 1.15 and 1.34 mm for the pixelated and non-pixelated directions; the average DOI resolution of the second row of pseudo-pixels was 5.1 mm in full width at half maximum (FWHM); when using the energy-weighted average of the earliest four-time stamps, the best CTR of 350 ps was achieved. Applying a broader energy window of 250-700 keV only slightly degrades the DOI resolution while maintaining the intrinsic resolution; the best CTR degrades to 410 ps. CONCLUSIONS: The proposed hybrid detector concept was verified, and a prototype detector showed high performance for 3D positioning and timing resolution. The novel detector concept shows promise for preclinical and clinical PET scanners with DOI capability.

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We investigate a highly multiplexing readout for depth-of-interaction (DOI) and time-of-flight PET detector consisting of an N×N crystals whose light outputs at the front and back ends are detected by using silicon photomultipliers (SiPM). The front N×N SiPM array is read by using a stripline (SL) configured to support discrimination of the row position of the signal-producing crystal. The back N×N SiPM array is similarly read by an SL for column discrimination. Hence, the detector has only four outputs. We built 4×4 and 8×8 detector modules (DM) by using 3.0×3.0×20 mm3 lutetium-yttrium oxyorthosilicates. The outputs were sampled and processed offline. For both DMs, crystal discrimination was successful. For the 4×4 DM, we obtained an average energy resolution (ER) of 14.1%, an average DOI resolution of 2.5 mm, a non DOI-corrected coincidence resolving time (CRT), measured in coincidence with a single-pixel reference detector, of about 495 ps. For the 8×8 DM, the average ER, average DOI resolution and average CRT were 16.4%, 2.9 mm, and 641 ps, respectively. We identified the intercrystal scattering as a probable cause for the CRT deterioration when the DM was increased from 4×4 to 8×8.

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BACKGROUND: High-resolution brain positron emission tomography (PET) scanner is emerging as a significant and transformative non-invasive neuroimaging tool to advance neuroscience research as well as improve diagnosis and treatment in neurology and psychiatry. Time-of-flight (TOF) and depth-of-interaction (DOI) information provide markedly higher PET imaging performance by increasing image signal-to-noise ratio and mitigating spatial resolution degradation due to parallax error, respectively. PET detector modules that utilize light sharing can inherently carry DOI information from the multiple timestamps that are generated per gamma event. The difference between two timestamps that are triggered by scintillation photons traveling in opposite directions signifies the event's depth-dependent optical photon TOF (oTOF). However, light leak at the crystal-readout interface substantially degrades the resolution of this oTOF-based depth encoding. PURPOSE: We demonstrate the feasibility of oTOF-based depth encoding by mitigating light leak in single-ended-readout Prism-PET detector modules using tapered crystals. Minimizing light leak also improved both energy-based DOI and coincidence timing resolutions. METHODS: The tapered Prism-PET module consists of a 16  × $\times$  16 array of 1.5  × $\times$  1.5  × $\times$  20  mm 3 ${\rm {mm}}^3$ lutetium yttrium oxyorthosillicate (LYSO) crystals, which are tapered down to 1.2  × $\times$  1.2  mm 2 ${\rm {mm}}^2$ at the crystal-readout interface. The LYSO array couples 4-to-1 to an 8  × $\times$  8 array of 3  × $\times$  3  mm 2 ${\rm {mm}}^2$ silicon photomultiplier (SiPM) pixels on the tapered end and to a segmented prismatoid light guide array on the opposite end. Performance of tapered and non-tapered Prism-PET detectors was experimentally characterized and evaluated by measuring flood histogram, energy resolution, energy-, and oTOF-based DOI resolutions, and coincidence timing resolution. Sensitivities of scanners using different Prism-PET detector designs were simulated using Geant4 application for tomographic emission (GATE). RESULTS: For the tapered (non-tapered) Prism-PET module, the measured full width at half maximum (FWHM) energy, timing, energy-based DOI, and oTOF-based DOI resolutions were 8.88 (11.18)%, 243 (286) ps, 2.35 (3.18) mm, and 5.42 (13.87) mm, respectively. The scanner sensitivities using non-tapered and tapered crystals, and 10 rings of detector modules, were simulated to be 30.9 and 29.5 kcps/MBq, respectively. CONCLUSIONS: The tapered Prism-PET module with minimized light leak enabled the first experimental report of oTOF-based depth encoding at the detector module level. It also enabled the utilization of thinner (i.e., 0.1 mm) inter-crystal spacing with barium sulfate as the reflector while also improving energy-based DOI and timing resolutions.

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Objective. We propose a single-ended readout, multi-resolution detector design that can achieve high spatial, depth-of-interaction (DOI), and time-of-flight (TOF) resolutions, as well as high sensitivity for human brain-dedicated positron emission tomography (PET) scanners.Approach. The detector comprised two layers of LYSO crystal arrays and a lightguide in between. The top (gamma ray entrance) layer consisted of a 16 × 16 array of 1.53 × 1.53 × 6 mm3LYSO crystals for providing high spatial resolution. The bottom layer consisted of an 8 × 8 array of 3.0 × 3.0 × 15 mm3LYSO crystals that were one-to-one coupled to an 8 × 8 multipixel photon counter (MPPC) array for providing high TOF resolution. The 2 mm thick lightguide introduces inter-crystal light sharing that causes variations of the light distribution patterns for high DOI resolution. The detector was read out by a PETsys TOFPET2 application-specific integrated circuit.Main result. The top and bottom layers were distinguished by a convolutional neural network with 97% accuracy. All crystals in the top and bottom layers were resolved. The inter-crystal scatter (ICS) events in the bottom layer were identified, and the measured average DOI resolution of the bottom layer was 4.1 mm. The coincidence time resolution (CTR) for the top-top, top-bottom, and bottom-bottom coincidences was 476 ps, 405 ps, and 298 ps, respectively. When ICS events were excluded from the bottom layer, the CTR of the bottom-bottom coincidence was 277 ps.Significance. The top layer of the proposed two-layer detector achieved a high spatial resolution and the bottom layer achieved a high TOF resolution. Together with its high DOI resolution and detection efficiency, the proposed detector is well suited for next-generation high-performance brain-dedicated PET scanners.

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Objective. The high production cost of commonly used lutetium-based fast scintillators and the development of silicon photomultipliers technology have made bismuth germanate (BGO) a promising candidate for time-of-flight positron emission tomography (TOF PET) detectors owing to its generation of prompt Cherenkov photons. However, using BGO as a hybrid scintillator is disadvantageous owing to its low photon statistics and distribution that does not conform well to a single Gaussian. To mitigate this, a proposal was made to increase the likelihood of detecting the first Cherenkov photons by positioning two photosensors in opposition at the entrance and exit faces of the scintillator and subsequently selectively picking an earlier timestamp. Nonetheless, the timing variation arising from the photon transit time remains affected by the entire length of the crystal, thereby presenting a possibility for further enhancement.Approach. In this study, we aimed to improve the timing performance of the dual-ended BGO Cherenkov TOF PET detector by capitalizing on the synergistic advantages of applying depth-of-interaction (DOI) information and crystal surface finishes or reflector properties. A dual-ended BGO detector was implemented using a 3 × 3 × 15 mm3BGO crystal. Coincidence events were acquired against a 3 × 3 × 3 mm3LYSO:Ce:Mg reference detector. The timing performance of the dual-ended BGO detectors was analyzed using conventionally proposed timestamp methods before and after DOI correction.Results. Through a DOI-based correction of photon transit time spread, we demonstrated a further improvement in the timing resolution of the BGO-based Cherenkov TOF PET detector utilizing a dual-ended detector configuration and adaptive arrival time pickoff. We achieved further improvements in timing resolution by correcting the offset spread induced by the fluctuation of timing signal rise time in the dual-ended detector.Significance. Although polishing the crystal surface was still favorable in terms of full-width-half-maximum value, incorporating DOI information from the unpolished crystal to compensate for photon travel time facilitated additional enhancement in the overall timing performance, thereby surpassing that achieved with the polished crystal.

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BACKGROUND AND OBJECTIVE: For positron emission tomography (PET) scanners with depth-of-interaction (DOI) measurement, the DOI rebinning method that utilizes DOI information to process the projection data is critical to image quality. Current DOI rebinning methods map coincidence events onto the rebinned sinogram based on the correlation of lines of response (LOR). This study aims to incorporate prior radioactivity distribution of the imaging object into DOI rebinning to obtain better image quality. METHODS: A DOI rebinning method based on both geometric and activity weights was proposed to assign coincidence events to the rebinned sinogram defined by a virtual ring. The geometric weights, representing the correlation between LORs, were calculated based on the areas of intersection. The activity weights, reflecting the activity distribution of the imaging object, were derived from the previous reconstructed image. RESULTS: Monte Carlo simulation data from four phantoms, including the image quality phantom, Derenzo phantom, and two rat-like ROBY phantoms, was used to evaluate the proposed method. The recovery coefficient (RC), contrast recovery coefficient (CRC), structural similarity index measure (SSIM), and peak signal-to-noise ratio (PSNR) were used as image quality metrics. Compared to other DOI rebinning methods, the proposed method achieved the highest RC (maximum improvement of 32%) and CRC at the same noise level and was also optimal in terms of the SSIM and PSNR. Meanwhile, incorporating the prior activity distribution into DOI rebinning also improved the image reconstruction speed. CONCLUSIONS: This work developed a new DOI rebinning method combining the correlation of LORs with the prior activity distribution, achieving relatively optimal image quality and reconstruction speed. Furthermore, it still needs to be evaluated on the actual equipment.

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In positron emission tomography (PET), parallax errors degrade spatial resolution. The depth of interaction (DOI) information provides the position in the depth of the scintillator interacting with the γ-rays, thus reducing parallax errors. A previous study developed a Peak-to-Charge discrimination (PQD), which can separate spontaneous alpha decay in LaBr3:Ce. Since decay constant of GSO:Ce depends on Ce concentration, the PQD is expected to discriminate GSO:Ce scintillators with different Ce concentration. In this study, the PQD-based DOI detector system was developed, which can be processed online and implemented in PET. A detector was composed of four layers of GSO:Ce crystals and a PS-PMT. The four crystals were obtained from both the top and bottom of ingots with a nominal Ce concentration of 0.5 mol% and 1.5 mol%. The PQD was implemented on the Xilinx Zynq-7000 SoC board with 8ch Flash ADC to gain real-time processing, flexibility, and expandability. The results showed that the mean Figure of Merits in 1D between four scintillators are 1.5, 0.99, 0.91 for layers between 1st-2nd, 2nd-3rd, and 3rd-4th respectively, and the mean Error Rate in 1D between four scintillators are 3.50%, 2.96%, 13.3%, and 1.88% for layers 1, 2, 3, and 4, respectively. In addition, the introduction of the 2D PQDs resulted in the mean Figure of Merits in 2D greater than 0.9 and the mean Error Rate in 2D less than 3% in all layers.

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Objective. We propose a novel four-layer depth-of-interaction (DOI) encoding phoswich detector using lutetium-yttrium oxyothosilicate (LYSO) and bismuth germanate (BGO) scintillator crystal arrays for high sensitivity and high spatial resolution small animal PET imaging.Approach. The detector was comprised of a stack of four alternating LYSO and BGO scintillator crystal arrays coupled to an 8 × 8 multi-pixel photon counter (MPPC) array and read out by a PETsys TOFPET2 application specific integrated circuit. The four layers from the top (gamma ray entrance) to the bottom (facing the MPPC) consisted of a 24 × 24 array of 0.99 × 0.99 × 6 mm3LYSO crystals, a 24 × 24 array of 0.99 × 0.99 × 6 mm3BGO crystals, a 16 × 16 array of 1.53 × 1.53 × 6 mm3LYSO crystals and a 16 × 16 array of 1.53 × 1.53 × 6 mm3BGO crystals.Main results. Events that occurred in the LYSO and BGO layers were first separated by measuring the pulse energy (integrated charge) and duration (time over threshold (ToT)) from the scintillation pulses. Convolutional neural networks (CNNs) were then used to distinguish between the top and lower LYSO layers and between the upper and bottom BGO layers. Measurements with the prototype detector showed that our proposed method successfully identified events from all four layers. The CNN models achieved a classification accuracy of 91% for distinguishing the two LYSO layers and 81% for distinguishing the two BGO layers. The measured average energy resolution was 13.1% ± 1.7% for the top LYSO layer, 34.0% ± 6.3% for the upper BGO layer, 12.3% ± 1.3% for the lower LYSO layer, and 33.9% ± 6.9% for the bottom BGO layer. The timing resolution between each individual layer (from the top to the bottom) and a single crystal reference detector was 350 ps, 2.8 ns, 328 ps, and 2.1 ns respectively.Significance. In conclusion, the proposed four-layer DOI encoding detector achieved high performance and is an attractive choice for next-generation high sensitivity and high spatial resolution small animal positron emission tomography systems.

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Cherenkov light can improve the timing resolution of Positron Emission Tomography (PET) radiation detectors, thanks to its prompt emission. Coincidence time resolutions (CTR) of ~30 ps were recently reported when using 3.2 mm-thick Cherenkov emitters. However, sufficient detection efficiency requires thicker crystals, causing the timing resolution to be degraded by the optical propagation inside the crystal. We report on depth-of-interaction (DOI) correction to mitigate the time-jitter due to the photon time spread in Cherenkov-based radiation detectors. We simulated the Cherenkov and scintillation light generation and propagation in 3 × 3 mm2 lead fluoride, lutetium oxyorthosilicate, bismuth germanate, thallium chloride, and thallium bromide. Crystal thicknesses varied from 9 to 18 mm with a 3-mm step. A DOI-based time correction showed a 2-to-2.5-fold reduction of the photon time spread across all materials and thicknesses. Results showed that highly refractive crystals, though producing more Cherenkov photons, were limited by an experimentally obtained high-cutoff wavelength and refractive index, restricting the propagation and extraction of Cherenkov photons mainly emitted at shorter wavelengths. Correcting the detection time using DOI information shows a high potential to mitigate the photon time spread. These simulations highlight the complexity of Cherenkov-based detectors and the competing factors in improving timing resolution.

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BACKGROUND: Small-animal positron emission tomography (PET) systems are widely used in molecular imaging research and drug development. There is also growing interest in organ-dedicated clinical PET systems. In these small-diameter PET systems, the measurement of the depth-of-interaction (DOI) of annihilation photons in scintillation crystals allows for the correction of parallax error in PET system, leading to an improvement on the spatial resolution uniformity. The DOI information is also useful for improving the timing resolution of PET system as it enables the correction of DOI-dependent time walk in the arrival time difference measurement of annihilation photon pairs. The dual-ended readout scheme is one of the most widely investigated DOI measurement methods, which collects visible photons using a pair of photosensors located at both ends of the scintillation crystal. Although the dual-ended readout allows for simple and accurate DOI estimation, it requires twice the number of photosensors compared to the single-ended readout scheme. PURPOSE: To effectively reduce the number of photosensors in a dual-ended readout scheme, we propose a novel PET detector configuration that employs 45° tilted and sparsely arranged silicon photomultipliers (SiPMs). In this configuration, the angle between the scintillation crystal and SiPM is 45°. Therefore, and thus, the diagonal of the scintillation crystal matches one of the lateral sides of the SiPM. Accordingly, it allows for the use of SiPM device larger than the scintillation crystal, thereby improving light collection efficiency with a higher fill factor and reducing SiPM quantity. In addition, all scintillation crystals can achieve more uniform performance than other dual-ended readout methods with a sparse SiPM arrangement because 50% of the scintillation crystal cross section is commonly in contact with the SiPM. METHODS: To demonstrate the feasibility of our proposed concept, we implemented a PET detector that employs a 4 × ${\rm{\;}} \times \;$ 4 LSO block with a single crystal dimension of 3.03 × 3.03 × 20 mm3 and a 45° tilted SiPM array. The 45° tilted SiPM array consists of 2 × 3 SiPM elements at the top ("Top SiPM") and 3 × 2 SiPM elements at the bottom ("Bottom SiPM"). Each crystal element of the 4 × 4 LSO block is optically coupled with each quarter section of the Top SiPM and Bottom SiPM pair. To characterize the performance of the PET detector, the energy, DOI, and timing resolution were measured for all 16 crystals. The energy data was obtained by summing all the charges from the Top SiPMs and Bottom SiPMs, and the DOI resolution was measured by irradiating the side of the crystal block at five different depths (2, 6, 10, 14, and 18 mm). The timing was estimated by averaging the arrival time of the annihilation photons measured at the Top SiPMs and Bottom SiPMs (Method 1). The DOI-dependent time-walk effect was further corrected by using DOI information and statistical variations in the trigger times at the Top SiPMs and Bottom SiPMs (Method 2). RESULTS: The average DOI resolution of the proposed PET detector was 2.5 mm, thereby resolving the DOI at five different depths, and the average energy resolution was 16% full width at half maximum (FWHM). When Methods 1 and 2 were applied, the coincidence timing resolutions were 448 and 411 ps FWHM, respectively. CONCLUSIONS: We expect that our novel low-cost PET detector design with 45° tilted SiPMs and a dual-ended readout scheme would be a suitable solution for constructing a high-resolution PET system with DOI encoding capability.

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Objective. Small-animal positron emission tomography (PET) is a powerful preclinical imaging tool in animal model studies. The spatial resolution and sensitivity of current PET scanners developed for small-animal imaging need to be improved to increase the quantitative accuracy of preclinical animal studies. This study aimed to improve the identification capability of edge scintillator crystals of a PET detector which will enable to apply a crystal array with the same cross-section area as the active area of a photodetector for improving the detection area and thus reducing or eliminating the inter-detector gaps.Approach. PET detectors using crystal arrays with mixed lutetium yttrium orthosilicate (LYSO) and gadolinium aluminum gallium garnet (GAGG) crystals were developed and evaluated. The crystal arrays consisted of 31 × 31 array of 0.49 × 0.49 × 20 mm3crystals; they were read out by two silicon photomultiplier arrays with pixel sizes of 2 × 2 mm2that were placed at both ends of the crystal arrays. The second or first outermost layer of the LYSO crystals was replaced by GAGG crystals in the two crystal arrays. The two crystal types were identified using a pulse-shape discrimination technique to provide better edge crystal identification.Main results. Using the pulse shape discrimination technique, almost all (except for a few edge) crystals were resolved in the two detectors; high sensitivity was achieved by using the scintillator array and the photodetector with the same areas and achieved high resolution by using crystals with sizes equal to 0.49 × 0.49 × 20 mm3. Energy resolutions of 19.3 ± 1.8% and 18.9 ± 1.5%, depth-of-interaction resolutions of 2.02 ± 0.17 mm and 2.04 ± 0.18 mm, and timing resolutions of 1.6 ± 0.2 ns and 1.5 ± 0.2 ns were achieved by the two detectors, respectively.Significance. In summary, novel three-dimensional high-resolution PET detectors consisting of a mixture of LYSO and GAGG crystals were developed. The detectors significantly improve the detection area with the same photodetectors and thus improve the detection efficiency.

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BACKGROUND: Positron emission tomography (PET) has had a transformative impact on oncological and neurological applications. However, still much of PET's potential remains untapped with limitations primarily driven by low spatial resolution, which severely hampers accurate quantitative PET imaging via the partial volume effect (PVE). PURPOSE: We present experimental results of a practical and cost-effective ultra-high resolution brain-dedicated PET scanner, using our depth-encoding Prism-PET detectors arranged along a compact and conformal gantry, showing substantial reduction in PVE and accurate radiotracer uptake quantification in small regions. METHODS: The decagon-shaped prototype scanner has a long diameter of 38.5 cm, a short diameter of 29.1 cm, and an axial field-of-view (FOV) of 25.5 mm with a single ring of 40 Prism-PET detector modules. Each module comprises a 16 × 16 array of 1.5 × 1.5 × 20-mm3 lutetium yttrium oxyorthosillicate (LYSO) scintillator crystals coupled 4-to-1 to an 8 × 8 array of silicon photomultiplier (SiPM) pixels on one end and to a prismatoid light guide array on the opposite end. The scanner's performance was evaluated by measuring depth-of-interaction (DOI) resolution, energy resolution, timing resolution, spatial resolution, sensitivity, and image quality of ultra-micro Derenzo and three-dimensional (3D) Hoffman brain phantoms. RESULTS: The full width at half maximum (FWHM) DOI, energy, and timing resolutions of the scanner are 2.85 mm, 12.6%, and 271 ps, respectively. Not considering artifacts due to mechanical misalignment of detector blocks, the intrinsic spatial resolution is 0.89-mm FWHM. Point source images reconstructed with 3D filtered back-projection (FBP) show an average spatial resolution of 1.53-mm FWHM across the entire FOV. The peak absolute sensitivity is 1.2% for an energy window of 400-650 keV. The ultra-micro Derenzo phantom study demonstrates the highest reported spatial resolution performance for a human brain PET scanner with perfect reconstruction of 1.00-mm diameter hot-rods. Reconstructed images of customized Hoffman brain phantoms prove that Prism-PET enables accurate radiotracer uptake quantification in small brain regions (2-3 mm). CONCLUSIONS: Prism-PET will substantially strengthen the utility of quantitative PET in neurology for early diagnosis of neurodegenerative diseases, and in neuro-oncology for improved management of both primary and metastatic brain tumors.

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PET is a powerful molecular imaging technique that can provide functional information on living objects. However, the spatial resolution of PET imaging has been limited to around 1 mm, which makes it difficult to visualize mouse brain function in detail. Here, we report an ultrahigh-resolution small-animal PET scanner we developed that can provide a resolution approaching 0.6 mm to visualize mouse brain function with unprecedented detail. Methods: The ultrahigh-resolution small-animal PET scanner has an inner diameter of 52.5 mm and axial coverage of 51.5 mm. The scanner consists of 4 rings, each of which has 16 depth-of-interaction detectors. Each depth-of-interaction detector consists of a 3-layer staggered lutetium yttrium orthosilicate crystal array with a pitch of 1 mm and a 4 × 4 silicon photomultiplier array. The physical performance was evaluated in accordance with the National Electrical Manufacturers Association NU4 protocol. Spatial resolution was evaluated with phantoms of various resolutions. In vivo glucose metabolism imaging of the mouse brain was performed. Results: Peak absolute sensitivity was 2.84% with an energy window of 400-600 keV. The 0.55-mm rod structure of a resolution phantom was resolved using an iterative algorithm. In vivo mouse brain imaging with 18F-FDG clearly identified the cortex, thalamus, and hypothalamus, which were barely distinguishable in a commercial preclinical PET scanner that we used for comparison. Conclusion: The ultrahigh-resolution small-animal PET scanner is a promising molecular imaging tool for neuroscience research using rodent models.

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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° incidentγ-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-1and the noise equivalent count rate (NECR_2R) was 54.7 kcps at 6.0 kBq ml-1. Total sensitivity was 45.2 cps kBq-1and 48.4 cps kBq-1at 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.

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Objective.Time-of-flight-positron emission tomography would highly benefit from a coincidence time resolution (CTR) below 100 ps: improvement in image quality and patient workflow, and reduction of delivered dose are among them. This achievement proved to be quite challenging, and many approaches have been proposed and are being investigated for this scope. One of the most recent consists in combining different materials with complementary properties (e.g. high stopping power for 511 keVγ-ray and fast timing) in a so-calledheterostructure,metascintillatorormetapixel. By exploiting a mechanism of energy sharing between the two materials, it is possible to obtain a fraction of fast events which significantly improves the overall time resolution of the system.Approach.In this work, we present the progress on this innovative technology. After a simulation study using the Geant4 toolkit, aimed at understanding the optimal configuration in terms of energy sharing, we assembled four heterostructures with alternating plates of BGO and EJ232 plastic scintillator. We fabricated heterostructures of two different sizes (3 × 3 × 3 mm3and  3 × 3 × 15 mm3), each made up of plates with two different thicknesses of plastic plates. We compared the timing of these pixels with a standard bulk BGO crystal and a structure made of only BGO plates (layeredBGO).Main results.CTR values of 239 ± 12 ps and 197 ± 10 ps FWHM were obtained for the 15 mm long heterostructures with 100µm and 200µm thick EJ232 plates (both with 100µm thick BGO plates), compared to 271 ± 14 ps and 303 ± 15 ps CTR for bulk and layered BGO, respectively.Significance.Significant improvements in timing compared to standard bulk BGO were obtained for all the configurations tested. Moreover, for the long pixels, depth of interaction (DOI) collimated measurements were also performed, allowing to validate a simple model describing light transport inside the heterostructure.

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BACKGROUND: Most current whole-body positron emission tomography (PET) scanners use detectors with high timing resolution to measure the time-of-flight of two 511 keV photons, improving the signal-to-noise ratio of PET images. However, almost all current whole-body PET scanners use detectors without depth-encoding capability; therefore, their spatial resolution can be affected by the parallax effect. METHODS: In this work, four depth-encoding detectors consisting of LYSO arrays with crystals of 2.98 × 2.98 × 20 mm3, 2.98 × 2.98 × 30 mm3, 1.95 × 1.95 × 20 mm3, and 1.95 × 1.95 × 30 mm3, respectively, were read at both ends, with 6 × 6 mm2 silicon photomultiplier (SiPM) pixels in a 4 × 4 array being used. The timing signals of the detectors were processed individually using an ultrafast NINO application-specific integrated circuit (ASIC) to obtain good timing resolution. The 16 energy signals of the SiPM array were read using a row and column summing circuit to obtain four position-encoding energy signals. RESULTS: The four PET detectors provided good flood histograms in which all crystals could be clearly resolved, the crystal energy resolutions measured being 10.2, 12.1, 11.4 and 11.7% full width at half maximum (FWHM), at an average crystal depth of interaction (DOI) resolution of 3.5, 3.9, 2.7, and 3.0 mm, respectively. The depth dependence of the timing of each SiPM was measured and corrected, the timing of the two SiPMs being used as the timing of the dual-ended readout detector. The four detectors provided coincidence time resolutions of 180, 214, 239, and 263 ps, respectively. CONCLUSIONS: The timing resolution of the dual-ended readout PET detector was approximately 20% better than that of the single-ended readout detector using the same LYSO array, SiPM array, and readout electronics. The detectors developed in this work used long crystals with small cross-sections and provided good flood histograms, DOI, energy, and timing resolutions, suggesting that they could be used to develop whole-body PET scanners with high sensitivity, uniform high spatial resolution, and high timing resolution.

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PURPOSE: Quantitative in vivo molecular imaging of fine brain structures requires high-spatial resolution and high-sensitivity. Positron emission tomography (PET) is an attractive candidate to introduce molecular imaging into standard clinical care due to its highly targeted and versatile imaging capabilities based on the radiotracer being used. However, PET suffers from relatively poor spatial resolution compared to other clinical imaging modalities, which limits its ability to accurately quantify radiotracer uptake in brain regions and nuclei smaller than 3 mm in diameter. Here we introduce a new practical and cost-effective high-resolution and high-sensitivity brain-dedicated PET scanner, using our depth-encoding Prism-PET detector modules arranged in a conformal decagon geometry, to substantially reduce the partial volume effect and enable accurate radiotracer uptake quantification in small subcortical nuclei. METHODS: Two Prism-PET brain scanner setups were proposed based on our 4-to-1 and 9-to-1 coupling of scintillators to readout pixels using 1.5 × 1.5 × 20 $1.5 \times 1.5 \times 20$  mm3 and 0.987 × 0.987 × 20 $0.987 \times 0.987 \times 20$  mm3 crystal columns, respectively. Monte Carlo simulations of our Prism-PET scanners, Siemens Biograph Vision, and United Imaging EXPLORER were performed using Geant4 application for tomographic emission (GATE). National Electrical Manufacturers Association (NEMA) standard was followed for the evaluation of spatial resolution, sensitivity, and count-rate performance. An ultra-micro hot spot phantom was simulated for assessing image quality. A modified Zubal brain phantom was utilized for radiotracer imaging simulations of 5-HT1A receptors, which are abundant in the raphe nuclei (RN), and norepinephrine transporters, which are highly concentrated in the bilateral locus coeruleus (LC). RESULTS: The Prism-PET brain scanner with 1.5 mm crystals is superior to that with 1 mm crystals as the former offers better depth-of-interaction (DOI) resolution, which is key to realizing compact and conformal PET scanner geometries. We achieved uniform 1.3 mm full-width-at-half-maximum (FWHM) spatial resolutions across the entire transaxial field-of-view (FOV), a NEMA sensitivity of 52.1 kcps/MBq, and a peak noise equivalent count rate (NECR) of 957.8 kcps at 25.2 kBq/mL using 450-650 keV energy window. Hot spot phantom results demonstrate that our scanner can resolve regions as small as 1.35 mm in diameter at both center and 10 cm away from the center of the transaixal FOV. Both 5-HT1A receptor and norepinephrine transporter brain simulations prove that our Prism-PET scanner enables accurate quantification of radiotracer uptake in small brain regions, with a 1.8-fold and 2.6-fold improvement in the dorsal RN as well as a 3.2-fold and 4.4-fold improvement in the bilateral LC compared to the Biograph Vision and EXPLORER, respectively. CONCLUSIONS: Based on our simulation results, the proposed high-resolution and high-sensitivity Prism-PET brain scanner is a promising cost-effective candidate to achieve quantitative molecular neuroimaging of small but important brain regions with PET clinically viable.

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The best crystal identification (CI) algorithms proposed so far for phoswich detectors are based on adaptive filtering and pulse shape discrimination (PSD). However, these techniques require free running analog to digital converters, which is no longer possible with the ever increasing pixelization of new detectors. We propose to explore the dual-threshold time-over-threshold (ToT) technique, used to measure events energy and time of occurence, as a more robust solution for crystal identification with broad energy windows in phoswich detectors. In this study, phoswich assemblies made of various combinations of LGSO and LYSO scintillators with decay times in the range 30 to 65 ns were investigated for the LabPET II detection front-end. The electronic readout is based on a 4 × 8 APD array where pixels are individually coupled to charge sensitive preamplifiers followed by first order CR-RC shapers with 75 ns peaking time. Crystal identification data were sorted out based on the measurements of likeliness between acquired signals and a time domain model of the analog front-end. Results demonstrate that crystal identification can be successfully performed using a dual-threshold ToT scheme with a discrimination accuracy of 99.1% for LGSO (30 ns)/LGSO (45 ns), 98.1% for LGSO (65 ns)/LYSO (40 ns) and 92.1% for LYSO (32 ns)/LYSO (47 ns), for an energy window of [350-650] keV. Moreover, the method shows a discrimination accuracy >97% for the two first pairs and ~90% for the last one when using a wide energy window of [250-650] keV.

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We developed a time-based single-transmission-line readout method for time-of-flight positron emission tomography (PET) detectors. The 2D position of a silicon photomultiplier (SiPM) array was encoded in the upper and lower widths of a specially prepared L-shaped tag pulse followed by the original scintillation signal. A PET detector setup was configured using a 4 × 4 array of LSO crystals optically coupled one-to-one to a 4 × 4 SiPM array. Two pulse width modulator circuits were employed per SiPM anode signal channel and a total of 32 width-modulated digital pulses were summed and merged with a delayed common-cathode signal. The final output was analyzed using timestamps crossing two-level threshold voltages. All 16 crystals were clearly separated on a positioning map. The average energy and coincidence time resolutions were 15.0 ± 1.1% and 288.7 ± 29.3 ps after proper correction process, respectively. A 3D position decoding capability was also shown by the remarkable discrimination performance in a phoswich PET detector setup (LSO and LGSO), resulting from well-preserved scintillation signals. The proposed method enables a time-based single-channel readout with 3D gamma ray interaction position decoding capability without compromising on detector performance. This method provides gamma ray energy and arrival time information as well as 2D and depthwise interaction positions of the phoswich detectors through one channel readout. Thus, channels can be reduced by at least 4-5 times compared to typically employed charge-sharing-based position multiplexing method; this significantly reduces the burden of data acquisition on the PET system.

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In the wake of recent advancements in scintillator, photodetector, and low-noise fast electronics technologies, as well as in fast reconstruction software, positron emission tomography (PET) scanners have seen considerable improvements in spatial resolution, time resolution, and absolute sensitivity. To continue this trend, we present a helmet type PET brain scanner design that combines high solid angle coverage and double-ended readout of 30 mm-thick scintillator crystals to achieve excellent absolute sensitivity, depth of interaction resolution, and time resolution. This scanner comprises 598 detector arrays, each with 8 × 8 Lu1.8Y0.2SiO5:Ce (LYSO:Ce) crystals with dimensions 3.005 × 3.005 × 30 mm3one-to-one coupled on either end to silicon photomultipliers (SiPMs). Our Monte Carlo simulations based in the platform Geant4 predict that this scanner would attain an absolute sensitivity to a 35 cm line source placed at the center of the radial field of view of (17.1 ± 0.1)%, a depth of interaction resolution of (3.99 ± 0.05) mm, and a coincidence time resolution of (198 ± 5) ps. Our simulations also predict radial, tangential, and axial spatial resolutions at the center of the field of view of 3.3 mm, 3.1 mm, and 3.3 mm, respectively. As this set of simultaneous parameters compares favorably to today's most advanced clinical PET scanners and other proposed designs, this scanner has a good chance of becoming a preferred tool for high quality brain imaging.

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