Pushing the limit of BGO-based dual-ended Cherenkov PET detectors through photon transit time correction.

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.

Comparative study on gamma-ray detectors for in-situ ocean radiation monitoring system.

Large-sized crystals and state-of-the-art photosensors are desirable to cope with low environmental radioactivity (e.g., 1-2 Bq∙m-3137Cs in surface seawater) for homeland security purposes. We compared the performances of two different gamma-ray detector assemblies, GAGG crystal + silicon photomultiplier (SiPM) and NaI(Tl) crystal + photomultiplier tube, for our mobile in-situ ocean radiation monitoring system. We performed energy calibration, followed by water tank experiments with varying the depth of a137Cs point source. Experimental energy spectra were compared with MCNP-simulated spectra with identical setup and the consistency was validated. We finally assessed the detection efficiency and minimum detectable activity (MDA) of the detectors. Both GAGG and NaI detectors exhibited favorable energy resolutions (7.98 ± 0.13% and 7.01 ± 0.58% at 662 keV, respectively) and MDAs (33.1 ± 0.0645 and 13.5 ± 0.0327 Bq∙m-3 for 24-h 137Cs measurement, respectively). Matching the geometry of the GAGG crystal with that of the NaI crystal, the GAGG detector outperformed the NaI detector. The results demonstrated that the GAGG detector is potentially advantageous over the NaI detector in detection efficiency and compactness.

Performance evaluation of SimPET-L and SimPET-XL: MRI-compatible small-animal PET systems with rat-body imaging capability.

BACKGROUND: SimPET-L and SimPET-XL have recently been introduced with increased transaxial fields of view (FOV) compared with their predecessors (SimPET™ and SimPET-X), enabling whole-body positron emission tomography (PET) imaging of rats. We conducted performance evaluations of SimPET-L and SimPET-XL and rat-body imaging with SimPET-XL to demonstrate the benefits of increased axial and transaxial FOVs. PROCEDURES: The detector blocks in SimPET-L and SimPET-XL consist of two 4 × 4 silicon photomultiplier arrays coupled with 20 × 9 array lutetium oxyorthosilicate crystals. SimPET-L and SimPET-XL have an inner diameter (bore size) of 7.6 cm, and they are composed of 40 and 80 detector blocks yielding axial lengths of 5.5 and 11 cm, respectively. Each system was evaluated according to the National Electrical Manufacturers Association NU4-2008 protocol. Rat imaging studies, such as 18F-NaF and 18F-FDG PET, were performed using SimPET-XL. RESULTS: The radial resolutions at the axial center measured using the filtered back projection, 3D ordered-subset expectation maximization (OSEM), and 3D OSEM with point spread functions correction were 1.7, 0.82, and 0.82 mm FWHM in SimPET-L and 1.7, 0.91, and 0.91 mm FWHM in SimPET-XL, respectively. The peak sensitivities of SimPET-L and SimPET-XL were 6.30% and 10.4% for an energy window of 100-900 keV and 4.44% and 7.25% for a window of 250-750 keV, respectively. The peak noise equivalent count rate with an energy window of 250-750 keV was 249 kcps at 44.9 MBq for SimPET-L and 349 kcps at 31.3 MBq for SimPET-XL. In SimPET-L, the uniformity was 4.43%, and the spill-over ratios in air- and water-filled chambers were 5.54% and 4.10%, respectively. In SimPET-XL, the uniformity was 3.89%, and the spill-over ratio in the air- and water-filled chambers were 3.56% and 3.60%. Moreover, SimPET-XL provided high-quality images of rats. CONCLUSION: SimPET-L and SimPET-XL show adequate performance compared with other SimPET systems. In addition, their large transaxial and long axial FOVs provide imaging capability for rats with high image quality.

Depth-of-interaction positron emission tomography detector with 45° tilted silicon photomultipliers using dual-ended signal readout.

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.

Performance Evaluation of SimPET-X, a PET Insert for Simultaneous Mouse Total-Body PET/MR Imaging.

PURPOSE: In this study, a small animal PET insert (SimPET-X, Brightonix Imaging Inc.) for simultaneous PET/MR imaging studies is presented. This insert covers an 11-cm-long axial field-of-view (FOV) and enables imaging of mouse total-bodies and rat heads. PROCEDURES: SimPET-X comprises 16 detector modules to yield a ring diameter of 63 mm and an axial FOV of 110 mm. The detector module supports four detector blocks, each comprising two 4 × 4 SiPM arrays coupled with a 20 × 9 array of LSO crystals (1.2 × 1.2 × 10 mm3). The physical characteristics of SimPET-X were measured in accordance with the NEMA NU4-2008 standard protocol. In addition, we assessed the compatibility of SimPET-X with a small animal-dedicated MRI (M7, Aspect Imaging) and conducted phantom and animal studies. RESULTS: The radial spatial resolutions at the center based on 3D OSEM without and with the warm background were 0.73 mm and 0.99 mm, respectively. The absolute peak sensitivity of the system was 10.44% with an energy window of 100-900 keV and 8.27% with an energy window of 250-750 keV. The peak NECR and scatter fraction for the mouse phantom were 348 kcps at 26.2 MBq and 22.1% with an energy window of 250-750 keV, respectively. The standard deviation of pixel value in the uniform region of an NEMA IQ phantom was 4.57%. The spillover ratios for air- and water-filled chambers were 9.0% and 11.0%, respectively. In the hot-rod phantom image reconstructed using 3D OSEM-PSF, all small rods were resolved owing to the high spatial resolution of the SimPET-X system. There was no notable interference between SimPET-X and M7 MRI. SimPET-X provided high-quality mouse images with superior spatial resolution, sensitivity, and counting rate performance. CONCLUSION: SimPET-X yielded a remarkably improved sensitivity and NECR compared with SimPETTM.

Development and Initial Results of a Brain PET Insert for Simultaneous 7-Tesla PET/MRI Using an FPGA-Only Signal Digitization Method.

In study, we developed a positron emission tomography (PET) insert for simultaneous brain imaging within 7-Tesla (7T) magnetic resonance (MR) imaging scanners. The PET insert has 18 sectors, and each sector is assembled with two-layer depth-of-interaction (DOI)-capable high-resolution block detectors. The PET scanner features a 16.7-cm-long axial field-of-view (FOV) to provide entire human brain images without bed movement. The PET scanner early digitizes a large number of block detector signals at a front-end data acquisition (DAQ) board using a novel field-programmable gate array (FPGA)-only signal digitization method. All the digitized PET data from the front-end DAQ boards are transferred using gigabit transceivers via non-magnetic high-definition multimedia interface (HDMI) cables. A back-end DAQ system provides a common clock and synchronization signal for FPGAs over the HDMI cables. An active cooling system using copper heat pipes is applied for thermal regulation. All the 2.17-mm-pitch crystals with two-layer DOI information were clearly identified in the block detectors, exhibiting a system-level energy resolution of 12.6%. The PET scanner yielded clear hot-rod and Hoffman brain phantom images and demonstrated 3D PET imaging capability without bed movement. We also performed a pilot simultaneous PET/MR imaging study of a brain phantom. The PET scanner achieved a spatial resolution of 2.5 mm at the center FOV (NU 4) and a sensitivity of 18.9 kcps/MBq (NU 2) and 6.19% (NU 4) in accordance with the National Electrical Manufacturers Association (NEMA) standards.

[18F]CB251 PET/MR imaging probe targeting translocator protein (TSPO) independent of its Polymorphism in a Neuroinflammation Model.

The 18 kDa translocator protein (TSPO) has been proposed as a biomarker for the detection of neuroinflammation. Although various PET probes targeting TSPO have been developed, a highly selective probe for detecting TSPO is still needed because single nucleotide polymorphisms in the human TSPO gene greatly affect the binding affinity of TSPO ligands. Here, we describe the visualization of neuroinflammation with a multimodality imaging system using our recently developed TSPO-targeting radionuclide PET probe [18F]CB251, which is less affected by TSPO polymorphisms. Methods: To test the selectivity of [18F]CB251 for TSPO polymorphisms, 293FT cells expressing polymorphic TSPO were generated by introducing the coding sequences of wild-type (WT) and mutant (Alanine → Threonine at 147th Amino Acid; A147T) forms. Competitive inhibition assay was conducted with [3H]PK11195 and various TSPO ligands using membrane proteins isolated from 293FT cells expressing TSPO WT or mutant-A147T, representing high-affinity binder (HAB) or low-affinity binder (LAB), respectively. IC50 values of each ligand to [3H]PK11195 in HAB or LAB were measured and the ratio of IC50 values of each ligand to [3H]PK11195 in HAB to LAB was calculated, indicating the sensitivity of TSPO polymorphism. Cellular uptake of [18F]CB251 was measured with different TSPO polymorphisms, and phantom studies of [18F]CB251-PET using 293FT cells were performed. To test TSPO-specific cellular uptake of [18F]CB251, TSPO expression was regulated with pCMV-TSPO (or shTSPO)/eGFP vector. Intracranial lipopolysaccharide (LPS) treatment was used to induce regional inflammation in the mouse brain. Gadolinium (Gd)-DOTA MRI was used to monitor the disruption of the blood-brain barrier (BBB) and infiltration by immune cells. Infiltration of peripheral immune cells across the BBB, which exacerbates neuroinflammation to produce higher levels of neurotoxicity, was also monitored with bioluminescence imaging (BLI). Peripheral immune cells isolated from luciferase-expressing transgenic mice were transferred to syngeneic inflamed mice. Neuroinflammation was monitored with [18F]CB251-PET/MR and BLI. To evaluate the effects of anti-inflammatory agents on intracranial inflammation, an inflammatory cytokine inhibitor, 2-cyano-3, 12-dioxooleana-1, 9-dien-28-oic acid methyl ester (CDDO-Me) was administered in intracranial LPS challenged mice. Results: The ratio of IC50 values of [18F]CB251 in HAB to LAB indicated similar binding affinity to WT and mutant TSPO and was less affected by TSPO polymorphisms. [18F]CB251 was specific for TSPO, and its cellular uptake reflected the amount of TSPO. Higher [18F]CB251 uptake was also observed in activated immune cells. Simultaneous [18F]CB251-PET/MRI showed that [18F]CB251 radioactivity was co-registered with the MR signals in the same region of the brain of LPS-injected mice. Luciferase-expressing peripheral immune cells were located at the site of LPS-injected right striatum. Quantitative evaluation of the anti-inflammatory effect of CDDO-Me on neuroinflammation was successfully monitored with TSPO-targeting [18F]CB251-PET/MR and BLI. Conclusion: Our results indicate that [18F]CB251-PET has great potential for detecting neuroinflammation with higher TSPO selectivity regardless of polymorphisms. Our multimodal imaging system, [18F]CB251-PET/MRI, tested for evaluating the efficacy of anti-inflammatory agents in preclinical studies, might be an effective method to assess the severity and therapeutic response of neuroinflammation.

SimPET: a Preclinical PET Insert for Simultaneous PET/MR Imaging.

PURPOSE: SimPET/M7 system is a small-animal dedicated simultaneous positron emission tomography and magnetic resonance imaging (PET/MRI) scanner. The SimPET insert has been upgraded from its prototype with a focus on count rate performance and sensitivity. The M7 scanner is a 1-T permanent magnet-based compact MRI system without any cryogens. Here, we present performance evaluation results of SimPET along with the results of mutual interference evaluation and simultaneously acquired PET/MR imaging. PROCEDURES: Following NEMA NU 4-2008 standard, we evaluated the performance of the SimPET system. The M7 MRI compatibility of SimPET was also assessed by analyzing MRI images of a uniform phantom under different PET conditions and PET count rates with different MRI pulse sequences. Mouse imaging was performed including a whole-body 18F-NaF PET scan and a simultaneous PET/MRI scan with 64Cu-NOTA-ironoxide. RESULTS: The spatial resolution at center based on 3D OSEM without and with warm background was 0.7 mm and 1.45 mm, respectively. Peak sensitivity was 4.21 % (energy window = 250-750 keV). The peak noise equivalent count rate with the same energy window was 151 kcps at 38.4 MBq. The uniformity was 4.42 %, and the spillover ratios in water- and air-filled chambers were 14.6 % and 12.7 %, respectively. In the hot rod phantom image, 0.75-mm-diameter rods were distinguishable. There were no remarkable differences in the SNR and uniformity of MRI images and PET count rates with different PET conditions and MRI pulse sequences. In the whole-body 18F-NaF PET images, fine skeletal structures were well resolved. In the simultaneous PET/MRI study with 64Cu-NOTA-ironoxide, both PET and MRI signals changed before and after injection of the dual-modal imaging probe, which was evident with the exact spatiotemporal correlation. CONCLUSIONS: We demonstrated that the SimPET scanner has a high count rate performance and excellent spatial resolution. The combined SimPET/M7 enabled simultaneous PET/MR imaging studies with no remarkable mutual interference between the two imaging modalities.

Comparator-less PET data acquisition system using single-ended memory interface input receivers of FPGA.

In this study, we propose a linear field-programmable gate array (FPGA)-based charge measurement method by combining a charge-to-time converter (QTC) with a single-ended memory interface (SeMI) input receiver. The QTC automatically converts the input charge into a dual-slope pulse, which has a width proportional to the input charge. Dual-slope pulses are directly digitized by the FPGA input/output (I/O) buffers configured with SeMI input receivers. A proof-of-concept comparator-less QTC/SeMI data acquisition (DAQ) system, consisting of 132 energy and 33 timing channels, was developed and applied to a prototype brain-dedicated positron emission tomography (PET) scanner. The PET scanner consisted of 14 sectors, each containing 2 × 1 block detectors, and each block detector yielded four energy signals and one timing signal. Because a single QTC/SeMI DAQ system can receive signals from up to eight sectors, two QTC/SeMI DAQ systems connected using high-speed gigabit transceivers were used to acquire data from the PET scanner. All crystals in the PET block detectors, consisting of dual-layer stacked lutetium oxyorthosilicate (LSO) scintillation crystal and silicon photomultiplier arrays, were clearly resolved in the flood maps with an excellent energy resolution. The PET images of hot-rod, cylindrical, and two-dimensional Hoffman brain phantoms were also acquired using the prototype PET scanner and two QTC/SeMI DAQ systems.

Crystal surface and reflector optimization for the SiPM-based dual-ended readout TOF-DOI PET detector.

Silicon photomultipliers (SiPMs) are now widely used for positron emission tomography (PET) applications because of their high gain and low noise characteristics. The PET image quality has been improved with the advancement of time-of-flight (TOF) and depth-of-interaction (DOI) measurement techniques. For brain-dedicated PET systems, both TOF and DOI information are beneficial for enhancing the reconstructed PET image quality. In a previous study, we proposed SiPM-based dual-ended readout PET detectors that used a mean time method to achieve coincidence timing resolution (CTR) of 349 ps and DOI resolution of 2.9 mm. However, the coincidence timing resolution (CTR) was worse than 300 ps since the crystal surface and the reflector type were not optimized. This study aimed at investigating the optimal crystal surface treatment and the reflector material to achieve a sub-200 ps CTR and sub-3 mm DOI resolution with a dual-ended readout PET detector using an LYSO crystal (2.9 × 2.9 × 20 mm3). The scintillation light inside the LYSO crystal was read out by two SiPMs using the dual-ended readout method. The CTR and DOI resolution were measured with two different crystal surfaces (polished and saw-cut) and three different reflector material scenarios of ESR without grease (i.e., air coupling), ESR with optical grease and Teflon. We digitized the timing and energy signals by using a V775N TDC module (35 ps bit-1) and V965 QDC module, respectively. The combination of the saw-cut LYSO crystal and the ESR with air coupling resulted in the best CTR (188 ± 32 ps) and DOI resolution (2.9 ± 0.2 mm) with the dual-ended readout configuration. We concluded the dual-ended readout method in combination with the saw-cut crystal and the ESR reflector with air coupling can provide a sub-200 ps CTR and sub-3.0 mm DOI resolution simultaneously.

Time-based signal sampling using sawtooth-shaped threshold.

Energy measurement of scintillation pulses by using time-over-threshold (TOT) has advantages of low readout cost, low power consumption, and less complexity compared with conventional analog-to-digital converter (ADC) approaches. Therefore, TOT is attractive in positron emission tomography (PET) systems based on silicon photomultiplier (SiPM) arrays requiring many readout channels. However, poor energy resolution and linearity of TOT leads to degradation of the overall PET detector and system performance, which is unsuitable for high-performance PET systems. To overcome these limitations, we propose a novel time-based signal-sampling method, sawtooth threshold sampling (STS), for PET scintillation detectors. This method uses a sawtooth-shaped threshold signal generated adaptively to the input scintillation pulse. Based on the time difference between the rising and falling edges of the digital pulse train generated by comparing the input scintillation pulse to the sawtooth signal, we can estimate the input scintillation pulse amplitude at the several time points. We compared several curve-fitting and numerical integration methods for energy estimation from the STS samples. Coincidence data between two identical scintillation detectors composed of one-to-one coupled SiPM and LGSO crystal (3 × 3 × 20 mm3) was measured using the proposed STS circuit. For timing- and energy-resolution measurement, STS (10.5% ± 0.21% and 200 ± 5.8 ps) was superior than simple TOT (16.4% ± 0.52% and 224 ± 8.2 ps) and was similar to high-speed ADC (9.84% ± 0.11% and 193 ± 4.3 ps). In conclusion, the proposed method can be a cost-effective solution for data collection in future SiPM-based PET systems.

Achieving reliable coincidence resolving time measurement of PET detectors using multichannel waveform digitizer based on DRS4 chip.

Coincidence resolving time (CRT) is one of the most important physical-performance measures for positron emission tomography (PET), as reconstruction with accurate time-of-flight information enhances the lesion detectability in patient studies. Accordingly, various PET detector designs and high-performance front-end readout circuits have been actively investigated to improve timing performance. The resulting PET detectors are often evaluated using multichannel waveform digitizers for versatile data analysis of the output signals. However, we have found that inappropriate data acquisition (DAQ) using a multichannel waveform digitizer based on the domino-ring-sampler 4 (DRS4) chip can lead to a considerable error when determining CRT. To address this issue, we performed CRT measurements using a pair of Hamamatsu R9800 photomultiplier tube based PET detectors. Then, considering intra- and inter-chip sampling, we employed four different combinations of input channels into the CAEN DT5742B waveform digitizer and obtained 2D CRT maps according to the leading-edge discriminator threshold for assessing each DAQ scheme. The intra-chip CRT measurement exhibited unusual streak patterns in the 2D CRT map and yielded the artificially-low CRT information in PET detector pairs, whereas the inter-chip CRT measurement provided the reliable estimation of timing resolution. Further, we could prevent the high-frequency signal crosstalk among input channels within the DRS4 chip using the inter-chip CRT measurement. We expect that our findings will also be useful for achieving the reliable CRT measurements when using other single-chip-based multichannel waveform digitizers.

Proof-of-concept prototype time-of-flight PET system based on high-quantum-efficiency multianode PMTs.

PURPOSE: Time-of-flight (TOF) information in positron emission tomography (PET) scanners enhances the diagnostic power of PET scans owing to the increased signal-to-noise ratio of reconstructed images. There are numerous additional benefits of TOF reconstruction, including the simultaneous estimation of activity and attenuation distributions from emission data only. Exploring further TOF gains by using TOF PET scanners is important because it can broaden the applications of PET scans and expand our understanding of TOF techniques. Herein, we present a prototype TOF PET scanner with fine-time performance that can experimentally demonstrate the benefits of TOF information. METHODS: A single-ring PET system with a coincidence resolving time of 360 ps and a spatial resolution of 3.1/2.2 mm (filtered backprojection/ordered-subset expectation maximization) was developed. The scanner was based on advanced high-quantum-efficiency (high-QE) multianode photomultiplier tubes (PMTs). The impact of its fine-time performance was demonstrated by evaluating body phantom images reconstructed with and without TOF information. Moreover, the feasibility of the scanner as an experimental validator of TOF gains was verified by investigating the improvement of images under various conditions, such as the use of joint estimation algorithms of activity and attenuation, erroneous data correction factors (e.g., without normalization correction), and incompletely sampled data. RESULTS: The prototype scanner showed excellent performance, producing improved phantom images, when TOF information was employed in the reconstruction process. In addition, investigation of the TOF benefits using the phantom data in different conditions verified the usefulness of the developed system for demonstrating the practical effects of TOF reconstruction. CONCLUSIONS: We developed a prototype TOF PET scanner with good performance and a fine-timing resolution based on advanced high-QE multianode PMTs and demonstrated its feasibility as an experimental validator of TOF gains, suggesting its usefulness for investigating new applications of PET scans and clarifying TOF techniques in detail.

Hybrid charge division multiplexing method for silicon photomultiplier based PET detectors.

Silicon photomultiplier (SiPM) is widely utilized in various positron emission tomography (PET) detectors and systems. However, the individual recording of SiPM output signals is still challenging owing to the high granularity of the SiPM; thus, charge division multiplexing is commonly used in PET detectors. Resistive charge division method is well established for reducing the number of output channels in conventional multi-channel photosensors, but it degrades the timing performance of SiPM-based PET detectors by yielding a large resistor-capacitor (RC) constant. Capacitive charge division method, on the other hand, yields a small RC constant and provides a faster timing response than the resistive method, but it suffers from an output signal undershoot. Therefore, in this study, we propose a hybrid charge division method which can be implemented by cascading the parallel combination of a resistor and a capacitor throughout the multiplexing network. In order to compare the performance of the proposed method with the conventional methods, a 16-channel Hamamatsu SiPM (S11064-050P) was coupled with a 4 × 4 LGSO crystal block (3 × 3 × 20 mm3) and a 9 × 9 LYSO crystal block (1.2 × 1.2 × 10 mm3). In addition, we tested a time-over-threshold (TOT) readout using the digitized position signals to further demonstrate the feasibility of the time-based readout of multiplexed signals based on the proposed method. The results indicated that the proposed method exhibited good energy and timing performance, thus inheriting only the advantages of conventional resistive and capacitive methods. Moreover, the proposed method showed excellent pulse shape uniformity that does not depend on the position of the interacted crystal. Accordingly, we can conclude that the hybrid charge division method is useful for effectively reducing the number of output channels of the SiPM array.

Prototype pre-clinical PET scanner with depth-of-interaction measurements using single-layer crystal array and single-ended readout.

In this study, we developed a proof-of-concept prototype PET system using a pair of depth-of-interaction (DOI) PET detectors based on the proposed DOI-encoding method and digital silicon photomultiplier (dSiPM). Our novel cost-effective DOI measurement method is based on a triangular-shaped reflector that requires only a single-layer pixelated crystal and single-ended signal readout. The DOI detector consisted of an 18 × 18 array of unpolished LYSO crystal (1.47 × 1.47 × 15 mm3) wrapped with triangular-shaped reflectors. The DOI information was encoded by depth-dependent light distribution tailored by the reflector geometry and DOI correction was performed using four-step depth calibration data and maximum-likelihood (ML) estimation. The detector pair and the object were placed on two motorized rotation stages to demonstrate 12-block ring PET geometry with 11.15 cm diameter. Spatial resolution was measured and phantom and animal imaging studies were performed to investigate imaging performance. All images were reconstructed with and without the DOI correction to examine the impact of our DOI measurement. The pair of dSiPM-based DOI PET detectors showed good physical performances respectively: 2.82 and 3.09 peak-to-valley ratios, 14.30% and 18.95% energy resolution, and 4.28 and 4.24 mm DOI resolution averaged over all crystals and all depths. A sub-millimeter spatial resolution was achieved at the center of the field of view (FOV). After applying ML-based DOI correction, maximum 36.92% improvement was achieved in the radial spatial resolution and a uniform resolution was observed within 5 cm of transverse PET FOV. We successfully acquired phantom and animal images with improved spatial resolution and contrast by using the DOI measurement. The proposed DOI-encoding method was successfully demonstrated in the system level and exhibited good performance, showing its feasibility for animal PET applications with high spatial resolution and sensitivity.

Single transmission-line readout method for silicon photomultiplier based time-of-flight and depth-of-interaction PET.

We propose a novel single transmission-line readout method for whole-body time-of-flight positron emission tomography applications, without compromising on performance. The basic idea of the proposed multiplexing method is the addition of a specially prepared tag signal ahead of the scintillation pulse. The tag signal is a square pulse that encodes photon arrival time and channel information. The 2D position of a silicon photomultiplier (SiPM) array is encoded by the specific width and height of the tag signal. A summing amplifier merges the tag and scintillation signals of each channel, and the final output signal can be acquired with a one-channel digitizer. The feasibility and performance of the proposed method were evaluated using a 1:1 coupled detector consisting of 4 × 4 array of LGSO crystals and 16 channel SiPM. The sixteen 3 mm LGSO crystals were clearly separated in the crystal-positioning map with high reliability. The average energy resolution and coincidence resolving time were 11.31 ± 0.55% and 264.7 ± 10.7 ps, respectively. We also proved that the proposed method does not degrade timing performance with increasing multiplexing ratio. The two types of LGSO crystals (L0.95GSO and L0.20GSO) in phoswich detector were also clearly identified with the high-reliability using pulse shape discrimination, thanks to the well-preserved pulse shape information. In conclusion, the proposed multiplexing method allows decoding of the 3D interaction position of gamma rays in the scintillation detector with single-line readout.

Delay grid multiplexing: simple time-based multiplexing and readout method for silicon photomultipliers.

In this paper, we propose a fully time-based multiplexing and readout method that uses the principle of the global positioning system. Time-based multiplexing allows simplifying the multiplexing circuits where the only innate traces that connect the signal pins of the silicon photomultiplier (SiPM) channels to the readout channels are used as the multiplexing circuit. Every SiPM channel is connected to the delay grid that consists of the traces on a printed circuit board, and the inherent transit times from each SiPM channel to the readout channels encode the position information uniquely. Thus, the position of each SiPM can be identified using the time difference of arrival (TDOA) measurements. The proposed multiplexing can also allow simplification of the readout circuit using the time-to-digital converter (TDC) implemented in a field-programmable gate array (FPGA), where the time-over-threshold (ToT) is used to extract the energy information after multiplexing. In order to verify the proposed multiplexing method, we built a positron emission tomography (PET) detector that consisted of an array of 4 × 4 LGSO crystals, each with a dimension of 3 × 3 × 20 mm3, and one- to-one coupled SiPM channels. We first employed the waveform sampler as an initial study, and then replaced the waveform sampler with an FPGA-TDC to further simplify the readout circuits. The 16 crystals were clearly resolved using only the time information obtained from the four readout channels. The coincidence resolving times (CRTs) were 382 and 406 ps FWHM when using the waveform sampler and the FPGA-TDC, respectively. The proposed simple multiplexing and readout methods can be useful for time-of-flight (TOF) PET scanners.

Simultaneous Multiparametric PET/MRI with Silicon Photomultiplier PET and Ultra-High-Field MRI for Small-Animal Imaging.

UNLABELLED: Visualization of biologic processes at molecular and cellular levels has revolutionized the understanding and treatment of human diseases. However, no single biomedical imaging modality provides complete information, resulting in the emergence of multimodal approaches. Combining state-of-the-art PET and MRI technologies without loss of system performance and overall image quality can provide opportunities for new scientific and clinical innovations. Here, we present a multiparametric PET/MR imager based on a small-animal dedicated, high-performance, silicon photomultiplier (SiPM) PET system and a 7-T MR scanner. METHODS: A SiPM-based PET insert that has the peak sensitivity of 3.4% and center volumetric resolution of 1.92/0.53 mm(3) (filtered backprojection/ordered-subset expectation maximization) was developed. The SiPM PET insert was placed between the mouse body transceiver coil and gradient coil of a 7-T small-animal MRI scanner for simultaneous PET/MRI. Mutual interference between the MRI and SiPM PET systems was evaluated using various MR pulse sequences. A cylindric corn oil phantom was scanned to assess the effects of the SiPM PET on the MR image acquisition. To assess the influence of MRI on the PET imaging functions, several PET performance indicators including scintillation pulse shape, flood image quality, energy spectrum, counting rate, and phantom image quality were evaluated with and without the application of MR pulse sequences. Simultaneous mouse PET/MRI studies were also performed to demonstrate the potential and usefulness of the multiparametric PET/MRI in preclinical applications. RESULTS: Excellent performance and stability of the PET system were demonstrated, and the PET/MRI combination did not result in significant image quality degradation of either modality. Finally, simultaneous PET/MRI studies in mice demonstrated the feasibility of the developed system for evaluating the biochemical and cellular changes in a brain tumor model and facilitating the development of new multimodal imaging probes. CONCLUSION: We developed a multiparametric imager with high physical performance and good system stability and demonstrated its feasibility for small-animal experiments, suggesting its usefulness for investigating in vivo molecular interactions of metabolites, and cross-validation studies of both PET and MRI.

Evaluation of a silicon photomultiplier PET insert for simultaneous PET and MR imaging.

PURPOSE: In this study, the authors present a silicon photomultiplier (SiPM)-based positron emission tomography (PET) insert dedicated to small animal imaging with high system performance and robustness to temperature change. METHODS: The insert consists of 64 LYSO-SiPM detector blocks arranged in 4 rings of 16 detector blocks to yield a ring diameter of 64 mm and axial field of view of 55 mm. Each detector block consists of a 9 × 9 array of LYSO crystals (1.2 × 1.2 × 10 mm(3)) and a monolithic 4 × 4 SiPM array. The temperature of each monolithic SiPM is monitored, and the proper bias voltage is applied according to the temperature reading in real time to maintain uniform performance. The performance of this PET insert was characterized using National Electrical Manufacturers Association NU 4-2008 standards, and its feasibility was evaluated through in vivo mouse imaging studies. RESULTS: The PET insert had a peak sensitivity of 3.4% and volumetric spatial resolutions of 1.92 (filtered back projection) and 0.53 (ordered subset expectation maximization) mm(3) at center. The peak noise equivalent count rate and scatter fraction were 42.4 kcps at 15.08 MBq and 16.5%, respectively. By applying the real-time bias voltage adjustment, an energy resolution of 14.2% ± 0.3% was maintained and the count rate varied ≤1.2%, despite severe temperature changes (10-30 °C). The mouse imaging studies demonstrate that this PET insert can produce high-quality images useful for imaging studies on the small animals. CONCLUSIONS: The developed MR-compatible PET insert is designed for insertion into a narrow-bore magnetic resonance imaging scanner, and it provides excellent imaging performance for PET/MR preclinical studies.

Dual-Phase Tapped-Delay-Line Time-to-Digital Converter With On-the-Fly Calibration Implemented in 40 nm FPGA.

This paper describes two novel time-to-digital converter (TDC) architectures. The first is a dual-phase tapped-delay-line (TDL) TDC architecture that allows us to minimize the clock skew problem that causes the highly nonlinear characteristics of the TDC. The second is a pipelined on-the-fly calibration architecture that continuously compensates the nonlinearity and calibrates the fine times using the most up-to-date bin widths without additional dead time. The two architectures were combined and implemented in a single Virtex-6 device (ML605, Xilinx) for time interval measurement. The standard uncertainty for the time intervals from 0 to 20 ns was less than 12.83 ps-RMS (root mean square). The resolution (i.e., the least significant bit, LSB) of the TDC was approximately 10 ps at room temperature. The differential nonlinearity (DNL) values were [-1.0, 1.91] and [-1.0, 1.88] LSB and the integral nonlinearity (INL) values were [-2.20, 2.60] and [-1.63, 3.93] LSB for the two different TDLs that constitute one TDC channel. During temperature drift from 10 to 50(°)C, the TDC with on-the-fly calibration maintained the standard uncertainty of 11.03 ps-RMS.