Thy1-ApoE4/C/EBPß double transgenic mice act as a sporadic model with Alzheimer's disease.

Early onset familial Alzheimer's disease (FAD) with APP, PS1/2 (presenilins) mutation accounts for only a small portion of AD cases, and most are late-onset sporadic. However, majority of AD mouse models are developed to mimic the genetic cause of human AD by overexpressing mutated forms of human APP, PS1/2, and/or Tau protein, though there is no Tau mutation in AD, and no single mouse model recapitulates all aspects of AD pathology. Here, we report Thy1-ApoE4/C/EBPß double transgenic mouse model that demonstrates key AD pathologies in an age-dependent manner in absence of any human APP or PS1/2 mutation. Using the clinical diagnosis criteria, we show that this mouse model exhibits tempo-spatial features in AD patient brains, including progressive cognitive decline associated with brain atrophy, which is accompanied with extensive neuronal degeneration. Remarkably, the mice display gradual Aß aggregation and neurofibrillary tangles formation in the brain validated by Aß PET and Tau PET. Moreover, the mice reveal widespread neuroinflammation as shown in AD brains. Hence, Thy1-ApoE4/C/EBPß mouse model acts as a sporadic AD mouse model, reconstituting the major AD pathologies.

Development and performance of SIAT bPET: a high-resolution and high-sensitivity MR-compatible brain PET scanner using dual-ended readout detectors.

PURPOSE: Positron emission tomography/magnetic resonance imaging (PET/MRI) is a powerful tool for brain imaging, but the spatial resolution of the PET scanners currently used for brain imaging can be further improved to enhance the quantitative accuracy of brain PET imaging. The purpose of this study is to develop an MR-compatible brain PET scanner that can simultaneously achieve a uniform high spatial resolution and high sensitivity by using dual-ended readout depth encoding detectors. METHODS: The MR-compatible brain PET scanner, named SIAT bPET, consists of 224 dual-ended readout detectors. Each detector contains a 26 × 26 lutetium yttrium oxyorthosilicate (LYSO) crystal array of 1.4 × 1.4 × 20 mm3 crystal size read out by two 10 × 10 silicon photomultiplier (SiPM) arrays from both ends. The scanner has a detector ring diameter of 376.8 mm and an axial field of view (FOV) of 329 mm. The performance of the scanner including spatial resolution, sensitivity, count rate, scatter fraction, and image quality was measured. Imaging studies of phantoms and the brain of a volunteer were performed. The mutual interferences of the PET insert and the uMR790 3 T MRI scanner were measured, and simultaneous PET/MRI imaging of the brain of a volunteer was performed. RESULTS: A spatial resolution of better than 1.5 mm with an average of 1.2 mm within the whole FOV was obtained. A sensitivity of 11.0% was achieved at the center FOV for an energy window of 350-750 keV. Except for the dedicated RF coil, which caused a ~ 30% reduction of the sensitivity of the PET scanner, the MRI sequences running had a negligible effect on the performance of the PET scanner. The reduction of the SNR and homogeneity of the MRI images was less than 2% as the PET scanner was inserted to the MRI scanner and powered-on. High quality PET and MRI images of a human brain were obtained from simultaneous PET/MRI scans. CONCLUSION: The SIAT bPET scanner achieved a spatial resolution and sensitivity better than all MR-compatible brain PET scanners developed up to date. It can be used either as a standalone brain PET scanner or a PET insert placed inside a commercial whole-body MRI scanner to perform simultaneous PET/MRI imaging.

Low-count PET image reconstruction based on truncated inverse radon layer and U-shaped network.

Objective.Positron emission tomography (PET) is a functional imaging widely used in various applications such as tumour detection. PET image reconstruction is an ill-posed inverse problem, and the model-based iterative reconstruction methods commonly used in clinical practice have disadvantages such as long time consumption and low signal-to-noise ratio, especially at low doses.Approach.In this study, we propose a deep learning-based reconstruction method that is capable of reconstructing images directly from low-count sinograms. Our network consists of two parts, a truncated inverse radon layer for implementing domain transform and a U-shaped network for image enhancement.Main result.We validated our method on both simulation data and real data. Compared to ordered subset expectation maximization with a post-Guassian filter, the structural similarity can be improved from 0.9357 to 0.9613 and the peak signal-to-noise ratio can be improved by 5 dB.Significance.The proposed method can directly convert low-count sinograms into PET images, while obtaining improved image quality and having less time consumption than iterative reconstruction algorithms and the state-of-the-art convolutional neural network.

Edge effect reduction of high-resolution PET detectors using LYSO and GAGG phoswich crystals.

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.

Nicotine rebalances NAD+ homeostasis and improves aging-related symptoms in male mice by enhancing NAMPT activity.

Imbalances in NAD+ homeostasis have been linked to aging and various diseases. Nicotine, a metabolite of the NAD+ metabolic pathway, has been found to possess anti-inflammatory and neuroprotective properties, yet the underlying molecular mechanisms remained unknown. Here we find that, independent of nicotinic acetylcholine receptors, low-dose nicotine can restore the age-related decline of NAMPT activity through SIRT1 binding and subsequent deacetylation of NAMPT, thus increasing NAD+ synthesis. 18F-FDG PET imaging revealed that nicotine is also capable of efficiently inhibiting glucose hypermetabolism in aging male mice. Additionally, nicotine ameliorated cellular energy metabolism disorders and deferred age-related deterioration and cognitive decline by stimulating neurogenesis, inhibiting neuroinflammation, and protecting organs from oxidative stress and telomere shortening. Collectively, these findings provide evidence for a mechanism by which low-dose nicotine can activate NAD+ salvage pathways and improve age-related symptoms.

Effect of depth of interaction resolution on the spatial resolution of SIAT aPET.

Objective.Spatial resolution is a crucial parameter for a positron emission tomography (PET) scanner. The spatial resolution of a high-resolution small animal PET scanner is significantly influenced by the effect of depth of interaction (DOI) uncertainty. The aim of this work is to investigate the impact of DOI resolution on the spatial resolution of a small animal PET scanner called SIAT aPET and determine the required DOI resolution to achieve nearly uniform spatial resolution within the field of view (FOV).Approach. The SIAT aPET detectors utilize 1.0 × 1.0 × 20 mm3crystals, with an average DOI resolution of ∼2 mm. A default number of 16 DOI bins are used during data acquisition. First, a Na-22 point source was scanned in the center of the axial FOV with different radial offsets. Then, a Derenzo phantom was scanned at radial offsets of 0 and 15 mm in the center axial FOV. The measured DOI information was rebinned to 1, 2, 4 and 8 DOI bins to mimic different DOI resolutions of the detectors during image reconstruction.Main results. Significant artifacts were observed in images obtained from both the point source and Derenzo phantom when using only one DOI bin. When accurate measurement of DOI is not achieved, degradation in spatial resolution is more pronounced in the radial direction compared to tangential and axial directions for large radial offsets. The radial spatial resolutions at a 30 mm radial offset are 5.05, 2.62, 1.24, 0.86 and 0.78 mm when using 1, 2, 4, 8, or 16 DOI bins, respectively. The axial spatial resolution improved from ∼1.3 to 0.7 mm as the number of DOI bins increased from 1 to 16 at radial offsets from 0 to 25 mm. Two DOI bins are required to obtain images without significant artifacts. The required DOI resolution is about three times the crystal width of SIAT aPET to achieve a uniform submillimeter spatial resolution within the central 60 mm FOV and resolve the 1 mm rods of the Derenzo phantom at both positions.

Mutual interferences between SIAT aPET insert and a 3 T uMR 790 MRI scanner.

Objective.Dual-modality small animal PET/MR imaging provides temporally correlated information on two biochemical processes of a living object. An magnetic resonance imaging (MRI)-compatible small animal PET insert named Shenzhen Institutes of Advanced Technology (SIAT) aPET was developed by using dual-ended readout depth encoding detectors to simultaneously achieve a uniform high spatial resolution and high sensitivity at the SIAT. In this work, the mutual interferences between SIAT aPET and the 3 T uMR 790 MRI scanner of United Imaging was quantitatively evaluated.Approach.To minimize the mutual interferences, only the PET detectors and the readout electronics were placed inside the MRI scanner, the major signal processing electronic was placed in the corner of the MRI room and the auxiliary unit was placed in the MRI technical room. A dedicated mouse radio fRequency (RF) coil with a transmitter and receiver was developed for the PET insert. The effects of PET scanner on theB0andB1field of the MRI scanner and the quality of the MRI images were measured. The effects of MRI imaging on the performance of both the PET detectors and scanner were also measured.Main results.The electronic and mechanical components of the PET insert affected the homogeneity of theB0field. The PET insert had no effect on the homogeneity ofB1produced by the dedicated mouse coil but slightly reduced the strength ofB1. The mean and standard deviation of the RF noise map were increased by 2.2% and 11.6%, respectively, while the PET insert was placed in the MRI scanner and powered on. Eddy current was produced while the PET insert was placed in the MRI scanner, and it was further increased while the PET insert was powered on. Despite the above-mentioned interferences from the PET insert, the MR images of a uniform cylindrical water phantom showed that the changes in the signal-to-noise ratio (SNR) and homogeneity as the PET insert was placed in the MRI scanner were acceptable regardless of whether the PET insert was powered off or powered on. The maximum reduction of SNR was less than 11%, and the maximum reduction of homogeneity was less than 2.5% while the PET insert was placed inside the MRI scanner and powered on for five commonly used MRI sequences. MRI using gradient echo (GRE), spin echo (SE) and fast spin echo (FSE) sequences had negligible effects on the flood histograms and energy resolution of the PET detectors, as well as the spatial resolution and sensitivity of the PET scanner.Significance.The mutual interference between the SIAT aPET and the 3 T uMR 790 MRI scanner are acceptable. Simultaneous PET/MRI imaging of small animals can be performed with the two scanners.

Technical note: Comparison of arithmetic mean and energy-weighted mean flood histogram generation methods for dual-ended readout positron emission tomography detectors.

PURPOSE: Dual-ended readout pixelated scintillator array detectors can provide a suitable crystal resolvability and satisfactory depth of interaction (DOI), energy, and timing resolutions. Usually, the flood histogram measured by one-sided readout is depth dependent, and the flood histogram quality degrades as the distance between the interaction site and photodetector increases. Information measured by two photodetectors must be combined to obtain an improved flood histogram yielding a better PET scanner spatial resolution. METHODS: Two flood histogram generation algorithms for dual-ended readout of pixelated scintillator array detectors were compared by theoretical calculations and experimental measurements. The first algorithm is the arithmetic mean (AM) algorithm, which assigns the same weight to the flood histograms measured by photodetectors 1 and 2. The second algorithm is the energy-weighted mean (EWM) algorithm, which assigns each flood histogram a certain weight proportional to the energy measured by the photodetector. Theoretical equations were derived to determine the quality of the flood histograms obtained with these two algorithms. Experimental measurements were performed with an 18 × 18 lutetium-yttrium oxyorthosilicate (LYSO) array with a crystal size of 0.62 × 0.62 × 20 mm3 read out by two multi-anode photomultiplier tubes at both ends. Flood histograms of the whole array and five specific depths were compared between the above two algorithms. RESULTS: The theoretical results indicated that the flood histograms obtained with the EWM method matched those obtained with the AM method at the middle detector depth and were better at other detector depths when the distance (S) between the locations of the same crystal in the flood histograms measured by photodetectors 1 and 2 reached 0. The advantage of the EWM method decreased with increasing S value since the crystal position in the flood histogram obtained with the EWM method varies with the depth when S does not equal 0. The advantage of the EWM method decreased with increasing S value. The experimental results generally agreed with the theoretical predictions. Compared to the AM method, the EWM method provided a similar flood histogram at a depth of 10 mm but generated a better flood histogram at depths of 2 and 18 mm. Although an inverse correlation between Q (a quality factor representing the advantage of the EWM method) and S was observed, the variation in Q given the same S value was high. The average Q value at the same S still agreed with the theoretical predictions. CONCLUSIONS: Theoretical equations were derived, and experimental measurements were performed to compare two flood histogram generation algorithms for dual-ended readout PET detectors. The results indicated that the EWM method based on inverse variance weighting theory could provide better flood histograms than those provided by the AM method.

Ultra-high-resolution depth-encoding small animal PET detectors: Using GAGG and LYSO crystal arrays.

PURPOSE: Small animal positron emission tomography (PET) scanners are widely used in current biomedical research. The study aimed to develop high-efficiency and ultra-high-resolution detectors that could be used to develop a small animal PET scanner with high sensitivity and spatial resolution approaching to its physical limit. METHODS: Four crystal arrays were fabricated and measured in this study. Crystal arrays 1 and 2 consisted of 38 × 38 gadolinium aluminum gallium garnet (GAGG) and lutetium-yttrium oxyorthosilicate (LYSO) crystals of 0.4 × 0.4 × 20 mm3 size. Crystal array 3 consisted of 16 × 16 GAGG crystals of 0.3 × 0.3 × 20 mm3 size, and crystal array 4 consisted of 24 × 24 LYSO crystals 0.3 × 0.3 × 20 mm3 in size. The crystal arrays were dual-ended readouts using 8 × 8 silicon photomultiplier (SiPM) arrays of 2 × 2 mm2 pixel area. The SiPM array was readout using a signal multiplexing circuit to convert the 64 output signals into four position-encoding signals. The performances of the four detectors in terms of flood histogram, energy resolution, depth of interaction (DOI) resolution, and timing resolution were measured. RESULTS: The GAGG detectors provided better flood histograms, ∼30% higher photopeak amplitude, ∼20% higher energy resolution, ∼12% worse DOI resolution, and ∼15% worse timing resolution compared with LYSO detectors of the same crystal size. These four detectors provided DOI resolutions of <2 mm, energy resolutions of <22%, and timing resolutions of <1.6 ns. All crystals of 0.4 × 0.4 × 20 mm3 and 0.3 × 0.3 × 20 mm3 could be clearly resolved if the crystal array was 1 mm smaller in the four sides than that in the SiPM array. CONCLUSIONS: High DOI resolution PET detectors were developed using both GAGG and LYSO arrays with crystal sizes of 0.3 and 0.4 mm, respectively, and a length of 20 mm. The detectors can be used in the future to develop small animal PET scanners, especially dedicated mouse imaging PET scanners, which can simultaneously achieve high sensitivity and ultra-high spatial resolution.

High resolution detectors for whole-body PET scanners by using dual-ended readout.

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.

Physical and imaging performance of SIAT aPET under different energy windows and timing windows.

PURPOSE: The performance of small animal PET scanners depends on the energy window (EW) and timing window (TW). In National Electrical Manufacturers Association (NEMA) Standards Publication NU 4-2008, detailed procedures of the performance measurements are defined, but the EW and TW are not specified. In this work, the effects of EW and TW on the physical and imaging performance of Shenzhen Institute of Advanced Technology small animal PET (SIAT aPET) will be evaluated. METHODS: First, the flood histogram, energy resolution, and timing resolution were measured for a detector of SIAT aPET. Second, the spatial resolutions were measured with different EWs. Third, the sensitivities, the scatter fractions (SFs), and noise equivalent count rates (NECRs) of a mouse-sized phantom and a rat-sized phantom, the recovery coefficients (RCs) of rods of different sizes, and the percentage standard deviation (%STD) of the NEMA image quality phantom were measured for different EWs and TWs. Last, images of a hot rod phantom, a mouse heart, and a rat brain were acquired from the scanner with different EWs. RESULTS: The SIAT aPET detectors provided good flood histograms such that all but the corner crystals can be resolved even with lower energies of 250-350 keV, an average energy resolution of 21.1 ± 1.9%, and an average timing resolution of 2.63 ± 0.69 ns. The average spatial resolutions obtained with EWs of 250-350 keV and 450-550 keV are 0.68 mm and 0.75 mm. For EWs of 250-750 keV, 350-750 keV, and 450-750 keV with a fixed TW of 12 ns, the sensitivities at the center of field of view (FOV) are 16.0%, 11.9%, and 8.2%, the peak NECRs of a mouse-sized phantom are 355.6 kcps, 324.4 kcps, and 249.4 kcps, and the peak NECRs of a rat-sized phantom are 148.5 kcps, 144.3 kcps, and 117.7 kcps, respectively. For the TWs of 4 ns, 8 ns,12 ns, and 20 ns with a fixed EW of 350-750 keV, the sensitivities at the center of FOV are 9.6%, 11.4%, 11.9%, and 12.2%, the peak NECRs of a mouse-sized phantom are 260.1 kcps, 311.5 kcps, 324.4 kcps and 324.9 kcps, and the peak NECRs of a rat-sized phantom are 110.5 kcps, 137.3 kcps, 144.3 kcps, and 142.6 kcps, respectively. Narrowing the EW and TW improves the RCs of rods of all sizes, and the %STD of images obtained with different EWs and TWs are similar. Rods with diameter down to 0.8 mm can be visually resolved from images of the hot rod phantom obtained with different EWs. Images of mouse heart with high spatial resolution and rat brain with detail brain structure were obtained with different EWs. Images of both phantom and in vivo animals obtained with different EWs only showed subtle difference. CONCLUSION: The performance of SIAT aPET under different EWs and TWs was compared. The EW and TW affect the sensitivity, SF, and NECR but not the spatial resolution and animal images of SIAT aPET, which imply that careful optimization of the EW and TW is not required.

A thick semi-monolithic scintillator detector for clinical PET scanners.

Both monolithic and semi-monolithic scintillator positron emission tomography (PET) detectors can measure the depth of interaction with single-ended readout. Usually scintillators with a thickness of 10 mm or less are used since the position resolutions of the detectors degrade as the scintillator thickness increases. In this work, the performance of a 20 mm thick long rectangular semi-monolithic scintillator PET detector was measured by using both single-ended and dual-ended readouts with silicon photomultiplier (SiPM) arrays to provide a high detection efficiency. The semi-monolithic scintillator detector consists of nine lutetium-yttrium oxyorthosilicate slices measuring 1.37 × 51.2 × 20 mm3 with erythrocyte sedimentation rate foils of 0.065 mm thickness in between the slices. The SiPM array at each end of the scintillator detector consists of 16 × 4 SiPMs with a pixel size of 3.0 × 3.0 mm2 and a pitch of 3.2 mm. The 64 signals of each SiPM array are processed by using the TOFPET2 application-specific integrated circuit individually. All but the edge slices can be clearly resolved for the detectors with both single-ended and dual-ended readouts. The single-ended readout detector provides an average full width at half maximum (FWHM) Y (continuous direction) position resolution of 2.43 mm, Z (depth direction) position resolution of 4.77 mm, energy resolution of 25.7% and timing resolution of 779 ps. The dual-ended readout detector significantly improves the Y and Z position resolutions, slightly improves the energy and timing resolution at the cost of two photodetectors required for one detector module and provides an average FWHM Y position resolution of 1.97 mm, Z position resolution of 2.60 mm, energy resolution of 21.7% and timing resolution of 718 ps. The energy and timing resolution of the semi-monolithic scintillator detector in this work are worse than those of the segmented scintillator array detector and need to be further improved. The semi-monolithic scintillator detector described in this work reduces costs as compared to the traditional segmented scintillator array detector and reduces the edge effect as compared to the monolithic scintillator detector.

Design and performance of SIAT aPET: a uniform high-resolution small animal PET scanner using dual-ended readout detectors.

In this work, a small animal PET scanner named SIAT aPET was developed using dual-ended readout depth encoding detectors to simultaneously achieve high spatial resolution and high sensitivity. The scanner consists of four detector rings with 12 detector modules per ring; the ring diameter is 111 mm and the axial field of view (FOV) is 105.6 mm. The images are reconstructed using an ordered subset expectation maximization (OSEM) algorithm. The spatial resolution of the scanner was measured by using a 22Na point source at the center axial FOV with different radial offsets. The sensitivity of the scanner was measured at center axis of the scanner with different axial positions. The count rate performance of the system was evaluated by scanning mouse-sized and rat-sized phantoms. An ultra-micro hot-rods phantom and two mice injected with 18F-NaF and 18F-FDG were scanned on the scanner. An average depth of interaction (DOI) resolution of 1.96 mm, energy resolution of 19.1% and timing resolution of 1.20 ns were obtained for the detector. Average spatial resolutions of 0.82 mm and 1.16 mm were obtained up to a distance of 30 mm radially from the center of the FOV when reconstructing a point source in 1% and 10% warm backgrounds, respectively, using OSEM reconstruction with 16 subsets and 10 iterations. Sensitivities of 16.0% and 11.9% were achieved at center of the scanner for energy windows of 250-750 keV and 350-750 keV respectively. Peak noise equivalent count rates (NECRs) of 324 kcps and 144 kcps were obtained at an activity of 26.4 MBq for the mouse-sized and rat-sized phantoms. Rods of 1.0 mm diameter can be visually resolved from the image of the ultra-micro hot-rods phantom. The capability of the scanner was demonstrated by high quality in-vivo mouse images.

A GPU-accelerated fully 3D OSEM image reconstruction for a high-resolution small animal PET scanner using dual-ended readout detectors.

In this work, a GPU-accelerated fully 3D ordered-subset expectation maximization (OSEM) image reconstruction with point spread function (PSF) modeling was developed for a small animal PET scanner with a long axial field of view (FOV). Dual-ended readout detectors that provided high depth of interaction (DOI) resolution were used for the small animal PET scanner to simultaneously achieve uniform high spatial resolution and high sensitivity. First, we developed a novel sinogram generation method, in which the dimension of the sinogram was determined first and then an event was assigned to a few neighboring sinogram elements by using weights that are inversely proportional to the distance from the measured line of response (LOR) to the LOR of the sinogram elements. System geometric symmetry, precomputation of LOR-driven ray-tracing and texture memory were applied to accelerate the GPU-based reconstruction. We developed a spatially variant PSF model where the PSF parameters were obtained by using point source images measured at 18 positions in the FOV and a spatial invariant PSF model where the PSF parameters were obtained by using only one image measured at the center FOV. The performance of the image reconstruction method was evaluated by using simulated phantom data as well as phantom and in-vivo mouse data acquired on the scanner. The results showed that the proposed reconstruction method provided better spatial resolution, a higher contrast recovery coefficient and lower noise than the OSEM reconstruction and was more than 1000 times faster than the CPU-based reconstruction. The spatially variant PSF model did not result in any spatial resolution improvement compared to the spatial invariant PSF model, and thus, the latter that is much easier to implement in image reconstruction and can be used in a small animal PET scanner using detectors with very high DOI resolution. A whole body 18F-FDG mouse image with high resolution and a high contrast to noise ratio was obtained by using the proposed reconstruction method.

Performance comparison of two signal multiplexing readouts for SiPM-based pet detector.

PET scanners using SiPMs as photodetectors could have tens of thousands of SiPMs. To simplify the readout electronics, analog signal multiplexing readouts are always preferred to be used as early as possible. In this paper, two simple analog signal multiplexing readouts, a capacitive charge-division readout, and a resistive charge-division readout were evaluated and compared using dual-ended readout detectors based on 10 × 10 arrays of SensL MicroFJ-30035 SiPMs coupled to both ends of a 20 × 20 LYSO array with a pitch size of 1.5 mm and a length of 20 mm. The performance of the detectors were evaluated at different bias voltages (from 27.0 V to 30.5 V with an interval of 0.5 V) and a temperature of 22.8 °C. The flood histograms show that all the crystals in the LYSO array were clearly identified, whilst better flood histogram was obtained using the resistive charge-division readout. At a bias voltage of 29.5V, the flood histogram quality, energy resolution, DOI resolution, and timing resolution of the detector obtained using the capacitive charge-division readout were 3.28 ± 0.85, 18.9% ± 6.2%, 1.93 ± 0.20 mm, 1.25 ± 0.11 ns respectively, and those obtained using the resistive charge-division readout were 3.57 ± 0.81, 16.9% ± 6.5%, 1.96 ± 0.23 mm and 1.23 ± 0.07 ns, respectively. Overall, the detector with the resistive charge-division readout provided better performance.

Performance of a depth encoding PET detector module using light sharing and single-ended readout with SiPMs.

Detectors with depth encoding capability, good energy resolution and good timing resolution are required to develop high performance whole body and total body PET scanners. In this work, an 8 × 8 LYSO array with crystal size of 3 × 3 × 20 mm3 was fabricated by using coupling materials that included 5 mm optical glue, 9 mm triangle ESR reflector and 6 mm rectangle ESR reflector from the top to the bottom in between adjacent crystals in one direction. The LYSO array was single-ended read out by an 8 × 8 SiPM array with one-to-one coupling. Row and column summing circuit was used to read out the SiPM signals. The depth of interaction (DOI) of the detector was measured with the depth dependent light sharing between adjacent crystals while maintaining acceptable energy resolution and timing resolution. The performance of the detector module was evaluated. All crystals can be clearly resolved from the measured flood histogram. An average DOI resolution of 4.62 mm and an average timing resolution of 518 ps are obtained for events with E > 400 keV. The average energy resolution of the detector is 13.5%. This work provides a cost-effective depth encoding detector module that can be used to build high performance whole body and total body PET scanners in the future.

Performance of long rectangular semi-monolithic scintillator PET detectors.

PURPOSE: High-sensitivity and high-resolution depth-encoding positron emission tomography (PET) detectors are required to simultaneously improve the sensitivity and spatial resolution of a PET scanner so that the quantitative accuracy of PET studies can be improved. The semi-monolithic scintillator PET detector has the advantage of measuring the depth of interaction with single-ended readout as compared to the traditional pixelated scintillator detector, and significantly reducing the edge effect that deteriorates the spatial resolution at edges of the detector as compared to the monolithic scintillator detector if a long rectangular semi-monolithic detector is used. In this work, depth-encoding PET detector modules were built by using long rectangular semi-monolithic scintillators and single-ended readout by silicon photomultiplier (SiPM) arrays. The performance of the detector modules was measured. METHODS: The rectangular semi-monolithic scintillator detector has an outside dimension of 11.6 × 37.6 × 10 mm3 and consists of 11 polished lutetium-yttrium oxyorthosilicate (LYSO) slices measuring 1 × 37.6 × 10 mm3 . The enhanced specular reflector (ESR) was glued on both cross-sectional surfaces of each crystal slice. For the face opposite to the SiPM array and the two end faces of the detectors, surface treatments with and without black paint were implemented for performance comparison. The bottom face of the semi-monolithic detector was coupled to a 4 × 12 SiPM array that was grouped along rows and columns separately into 16 signals. The four row signals were used to identify the slices, and the 12 column signals were used to estimate the y (monolithic direction) and z (depth direction) interaction positions. The detector was irradiated at multiple positions with a collimated 511 keV gamma beam. The collimated beam was obtained with electronic collimation by using a 22 Na point source and a reference detector. The estimated width of the gamma beam is around 0.5 mm. The flood histogram for crystal slices was measured by using the center of gravity (COG) method. The COG method and the squared COG method were used for y position estimation. The standard deviation of the column signals, the ratio of maximum to the sum of the column signals, and the sum of squared column signals were used for z position estimation. RESULTS: All slices were clearly resolved from the measured flood histograms for both detectors with different crystal surface treatments. The estimated y positions roughly linearly change with the true positions at the middle of the detector until ~5 mm from both ends of the detector. The y and z spatial resolutions of the detectors were estimated for all middle positions located more than 5 mm from both ends of the detector. The squared COG method provides better y position resolution than the COG method. The three z estimation methods provide similar depth of interaction (DOI) resolution. Surface treatment with black paint significantly improves both y and z position resolution but degrades the energy and timing resolution of the detectors. The average full width half maxima (FWHM) spatial resolution is improved from 1.77 to 1.07 mm in the y direction by using the squared COG method and from 2.71 to 1.55 mm in the z direction by using the standard deviation method. The slice-based average energy resolution degrades from 15.8% to 24.9%. The timing resolution of the entire detector module degrades from 596 to 788 ps. CONCLUSION: The performance of rectangular semi-monolithic scintillator PET detectors with two different crystal surface treatments was measured. The detectors provide superior spatial resolution and depth-encoding capability and can be used to develop small animal and dedicated breast and brain PET scanners that can simultaneously achieve high spatial resolution, high sensitivity, and low cost.

Development of depth encoding small animal PET detectors using dual-ended readout of pixelated scintillator arrays with SiPMs.

PURPOSE: The performance of current small animal PET scanners is mainly limited by the detector performance and depth encoding detectors are required to develop PET scanner to simultaneously achieve high spatial resolution and high sensitivity. Among all depth encoding PET detector approaches, dual-ended readout detector has the advantage to achieve the highest depth of interaction (DOI) resolution and spatial resolution. Silicon photomultiplier (SiPM) is believed to be the photodetector of the future for PET detector due to its excellent properties as compared to the traditional photodetectors such as photomultiplier tube (PMT) and avalanche photodiode (APD). The purpose of this work is to develop high resolution depth encoding small animal PET detector using dual-ended readout of finely pixelated scintillator arrays with SiPMs. METHODS: Four lutetium-yttrium oxyorthosilicate (LYSO) arrays with 11 × 11 crystals and 11.6 × 11.6 × 20 mm3 outside dimension were made using ESR, Toray and BaSO4 reflectors. The LYSO arrays were read out with Hamamatsu 4 × 4 SiPM arrays from both ends. The SiPM array has a pixel size of 3 × 3 mm2 , 0.2 mm gap in between the pixels and a total active area of 12.6 × 12.6 mm2 . The flood histograms, DOI resolution, energy resolution and timing resolution of the four detector modules were measured and compared. RESULTS: All crystals can be clearly resolved from the measured flood histograms of all four arrays. The BaSO4 arrays provide the best and the ESR array provides the worst flood histograms. The DOI resolution obtained from the DOI profiles of the individual crystals of the four array is from 2.1 to 2.35 mm for events with E > 350 keV. The DOI ratio variation among crystals is bigger for the BaSO4 arrays as compared to both the ESR and Toray arrays. The BaSO4 arrays provide worse detector based DOI resolution. The photopeak amplitude of the Toray array had the maximum change with depth, it provides the worst energy resolution of 21.3%. The photopeak amplitude of the BaSO4 array with 80 µm reflector almost doesn't change with depth, it provides the best energy resolution of 12.9%. A maximum timing shift of 1.37 ns to 1.61 ns among the corner and the center crystals in the four arrays was obtained due to the use of resistor network readout. A crystal based timing resolution of 0.68 ns to 0.83 ns and a detector based timing resolution of 1.26 ns to 1.45 ns were obtained for the four detector modules. CONCLUSIONS: Four high resolution depth encoding small animal PET detectors were developed using dual-ended readout of pixelated scintillator arrays with SiPMs. The performance results show that those detectors can be used to build a small animal PET scanner to simultaneously achieve uniform high spatial resolution and high sensitivity.

A depth-encoding PET detector that uses light sharing and single-ended readout with silicon photomultipliers.

Detectors with depth-encoding capability and good timing resolution are required to develop high-performance whole-body or total-body PET scanners. In this work, depth-encoding PET detectors that use light sharing between two discrete crystals and single-ended readout with silicon photomultipliers (SiPMs) were manufactured and evaluated. The detectors consisted of two unpolished 3 × 3 × 20 mm3 LYSO crystals with different coupling materials between them and were read out by Hamamatsu 3 × 3 mm2 SiPMs with one-to-one coupling. The ratio of the energy of one SiPM to the total energy of two SiPMs was used to measure the depth of interaction (DOI). Detectors with different coupling materials in-between the crystals were measured in the singles mode in an effort to obtain detectors that can provide good DOI resolution. The DOI resolution and energy resolution of three types of detector were measured and the timing resolution was measured for the detector with the best DOI and energy resolution. The optimum detector, with 5 mm optical glue, a 9 mm triangular ESR and a 6 mm rectangular ESR in-between the unpolished crystals, provides a DOI resolution of 2.65 mm, an energy resolution of 10.0% and a timing resolution of 427 ps for events of E > 400 keV. The detectors simultaneously provide good DOI and timing resolution, and show great promise for the development of high-performance whole-body and total-body PET scanners.

Performance of a high-resolution depth encoding PET detector using barium sulfate reflector.

Small animal positron emission tomography (PET) is a well-established imaging modality in preclinical biomedical research. The performance of current small animal PET scanners is mainly limited by the detector performance and depth-encoding detectors are required to simultaneously achieve high spatial resolution and high sensitivity. In this work, the performance of a high-resolution dual-ended readout lutetium-yttrium oxyorthosilicate (LYSO) array using barium sulfate powder (BaSO4) as the inter-crystal reflector was measured for the first time and compared to that of a LYSO array using the most commonly used enhanced specular reflector (ESR). Both LYSO arrays have 18 × 18 crystals and the crystal size is about 0.62 × 0.62 × 20 mm3. The LYSO arrays are readout by two position-sensitive photomultiplier tubes (PSPMTs) from both ends. The flood histograms, energy resolution, depth of interaction (DOI) resolution and timing resolution were measured. The flood histograms of the LYSO array with BaSO4 reflector is much better than that of the LYSO array with ESR reflector. For the BaSO4 array, all crystals can be clearly resolved. For the ESR array, all crystals in one direction can be clearly resolved, but the edge 2-3 columns of the crystals in the other direction cannot be resolved. The average energy resolution of the BaSO4 and ESR arrays are 15.2% and 15.3%, respectively. The average DOI resolution of the BaSO4 array is 2.19 mm, which is 24% worse than the 1.76 mm DOI resolution of the ESR array. The timing resolution of both arrays is ~1.6 ns. The LYSO array with the new BaSO4 reflector provided an much better flood histogram in a high resolution dual-ended readout PET detectors as compared to the ESR array, and will be used to develop a small animal PET scanner that can simultaneously achieve uniform high spatial resolution, high sensitivity and low cost.