Small Animal Positron Emission Tomography Research Articles

Animal PET scanner with a large field of view is suitable for high-throughput scanning of rodents.

In preclinical studies, high-throughput positron emission tomography (PET) imaging, known as simultaneous multiple animal scanning, can reduce the time spent on animal experiments, the cost of PET tracers, and the risk of synthesis of PET tracers. It is well known that the image quality acquired by high-throughput imaging depends on the PET system. Herein, we investigated the influence of large field of view (FOV) PET scanner on high-throughput imaging. We investigated the influence of scanning four objects using a small animal PET scanner with a large FOV. We compared the image quality acquired by four objects scanned with the one acquired by one object scanned using phantoms and animals. We assessed the image quality with uniformity, recovery coefficient (RC), and spillover ratio (SOR), which are indicators of image noise, spatial resolution, and quantitative precision, respectively. For the phantom study, we used the NEMA NU 4-2008 image quality phantom and evaluated uniformity, RC, and SOR, and for the animal study, we used Wistar rats and evaluated the spillover in the heart and kidney. In the phantom study, four phantoms had little effect on imaging quality, especially SOR compared with that for one phantom. In the animal study as well, four rats had little effect on spillover from the heart muscle and kidney cortex compared with that for one rat. This study demonstrated that an animal PET scanner with a large FOV was suitable for high-throughput imaging. Thus, the large FOV PET scanner can support drug discovery and bridging research through rapid pharmacological and pathological evaluation.

Dynamic neuroreceptor positron emission tomography in non-anesthetized rats using point source based motion correction: A feasibility study with [11C]ABP688.

To prevent motion artifacts in small animal positron emission tomography (PET), animals are routinely scanned under anesthesia or physical restraint. Both may potentially alter metabolism and neurochemistry. This study investigates the feasibility of fully awake acquisition and subsequent absolute quantification of dynamic brain PET data via pharmacokinetic modelling in moving rats using the glutamate 5 receptor radioligand [11C]ABP688 and point source based motion correction. Five male rats underwent three dynamic [11C]ABP688 PET scans: two test-retest awake PET scans and one scan under anesthesia for comparison. Specific radioligand binding was determined via the simplified reference tissue model (reference: cerebellum) and outcome parameters BPND and R1 were evaluated in terms of stability and reproducibility. Test-retest measurements in awake animals gave reliable results with high correlations of BPND (y = 1.08 × -0.2, r = 0.99, p < 0.01) and an acceptable variability (mean over all investigated regions 15.7 ± 2.4%). Regional [11C]ABP688 BPNDs under awake and anesthetized conditions were comparable although in awake scans, absolute radioactive peak uptakes were lower and relative blood flow in terms of R1 was higher. Awake small animal PET with absolute quantification of neuroreceptor availability is technically feasible and reproducible thereby providing a suitable alternative whenever effects of anesthesia are undesirable, e.g. in sleep research.

Small animal PET imaging with the 68Ga-labeled pH (low) insertion peptide-like peptide YJL-4 in a triple-negative breast cancer mouse model

BackgroundThe aim of this study was to prepare a novel 68Ga-labeled pH (low) insertion peptide (pHLIP)-like peptide, YJL-4, and determine its value for the early diagnosis of triple-negative breast cancer (TNBC) via in vivo imaging of tumor-bearing nude mice. The novel peptide YJL-4 was designed using a template-assisted method and synthesized by solid-phase peptide synthesis. After modification with the chelator 1,4,7‑triazacyclononane-N,N′,N″-triacetic acid (NOTA), the peptide was labeled with 68Ga. Then, the biodistribution of 68Ga-YJL-4 in tumor-bearing nude mice was investigated, and the mice were imaged by small animal positron emission tomography (PET).ResultsThe radiochemical yield and radiochemical purity of 68Ga-YJL-4 were 89.5 ± 0.16% and 97.95 ± 0.06%, respectively. The biodistribution of 68Ga-YJL-4 in tumors (5.94 ± 1.27% ID/g, 6.72 ± 1.69% ID/g and 4.54 ± 0.58% ID/g at 1, 2 and 4 h after injection, respectively) was significantly greater than that of the control peptide in tumors at the corresponding time points (P < 0.01). Of the measured off-target organs, 68Ga-YJL-4 was highly distributed in the liver and blood. The small animal PET imaging results were consistent with the biodistribution results. The tumors were visualized by PET at 2 and 4 h after the injection of 68Ga-YJL-4. No tumors were observed in the control group.ConclusionsThe novel pHLIP family peptide YJL-4 can adopt an α-helical structure for easy insertion into the cell membrane in an acidic environment. 68Ga-YJL-4 was produced in high radiochemical yield with good stability and can target TNBC tissue. Moreover, the strong concentration of radioactive 68Ga-YJL-4 in the abdomen does not hinder the imaging of early TNBC.

Setup and characterisation according to NEMA NU 4 of the phenoPET scanner, a PET system dedicated for plant sciences

Objective. The phenoPET system is a plant dedicated positron emission tomography (PET) scanner consisting of fully digital photo multipliers with lutetium–yttrium oxyorthosilicate crystals and located inside a custom climate chamber. Here, we present the setup of phenoPET, its data processing and image reconstruction together with its performance. Approach. The performance characterization follows the national electrical manufacturers association (NEMA) standard for small animal PET systems with a number of adoptions due to the vertical oriented bore of a PET for plant sciences. In addition temperature stability and spatial resolution with a hot rod phantom are addressed. Main results. The spatial resolution for a 22Na point source at a radial distance of 5 mm to the center of the field-of-view (FOV) is 1.45 mm, 0.82 mm and 1.88 mm with filtered back projection in radial, tangential and axial direction, respectively. A hot rod phantom with 18F gives a spatial resolution of up to 1.6 mm. The peak noise-equivalent count rates are 550 kcps @ 35.08 MBq, 308 kcps @ 33 MBq and 45 kcps @ 40.60 MBq for the mouse, rat and monkey size scatter phantoms, respectively. The scatter fractions for these phantoms are 12.63%, 22.64% and 55.90%. We observe a peak sensitivity of up to 3.6% and a total sensitivity of up to S A,tot = 2.17%. For the NEMA image quality phantom we observe a uniformity of %STD = 4.22% with ordinary Poisson maximum likelihood expectation-maximization with 52 iterations. Here, recovery coefficients of 0.12, 0.64, 0.89, 0.93 and 0.91 for 1 mm, 2 mm, 3 mm, 4 mm and 5 mm rods are obtained and spill-over ratios of 0.08 and 0.14 for the water-filled and air-filled inserts, respectively. Significance. The phenoPET and its laboratory are now in routine operation for the administration of [11C]CO2 and non-invasive measurement of transport and allocation of 11C-labelled photoassimilates in plants.

Efficient Synthesis and HPLC-Based Characterization for Developing Vanadium-48-Labeled Vanadyl Acetylacetonate as a Novel Cancer Radiotracer for PET Imaging.

Bis(acetylacetonato)oxidovanadium(IV) [(VO(acac)2], generally known as vanadyl acetylacetonate, has been shown to be preferentially sequestered in malignant tissue. Vanadium-48 (48V) generated with a compact medical cyclotron has been used to label VO(acac)2 as a potential radiotracer in positron emission tomography (PET) imaging for the detection of cancer, but requires lengthy synthesis. Current literature protocols for the characterization of VO(acac)2 require macroscale quantities of reactants and solvents to identify products by color and to enable crystallization that are not readily adaptable to the needs of radiotracer synthesis. We present an improved method to produce vanadium-48-labeled VO(acac)2, [48V]VO(acac)2, and characterize it using high-performance liquid chromatography (HPLC) with radiation detection in combination with UV detection. The approach is suitable for radiotracer-level quantities of material. These methods are readily applicable for production of [48V]VO(acac)2. Preliminary results of preclinical, small-animal PET studies are presented.

Noninvasive Visualization of Amyloid-Beta Deposits in Alzheimer's Amyloidosis Mice via Fluorescence Molecular Tomography Using Contrast Agent.

Alzheimer's disease is pathologically featured by the accumulation of amyloid-beta (Aβ) plaque and neurofibrillary tangles. Compared to small animal positron emission tomography, optical imaging features nonionizing radiation, low cost, and logistic convenience. Optical detection of Aβ deposits is typically implemented by 2D macroscopic imaging and various microscopic techniques assisted with Aβ-targeted contrast agents. Here, we introduce fluorescence molecular tomography (FMT), a macroscopic 3D fluorescence imaging technique, convenient for in vivo longitudinal monitoring of the animal brain without the involvement of cranial window opening operation. This chapter aims to provide the protocols for FMT in vivo imaging of Aβ deposits in the brain of rodent model of Alzheimer's disease. The materials, stepwise method, notes, limitations of FMT, and emerging opportunities for FMT techniques are presented.

Small animal PET with spontaneous inhalation of 15O-labelled oxygen gases: Longitudinal assessment of cerebral oxygen metabolism in a rat model of neonatal hypoxic-ischaemic encephalopathy

Perinatal hypoxic-ischaemic encephalopathy (HIE) is the leading cause of irreversible brain damage resulting in serious neurological dysfunction among neonates. We evaluated the feasibility of positron emission tomography (PET) methodology with 15O-labelled gases without intravenous or tracheal cannulation for assessing temporal changes in cerebral blood flow ( CBF ) and cerebral metabolic rate for oxygen ( CMRO2 ) in a neonatal HIE rat model. Sequential PET scans with spontaneous inhalation of 15O-gases mixed with isoflurane were performed over 14 days after the hypoxic-ischaemic insult in HIE pups and age-matched controls. CBF and CMRO2 in the injured hemispheres of HIE pups remarkably decreased 2 days after the insult, gradually recovering over 14 days in line with their increase found in healthy controls according to their natural maturation process. The magnitude of hemispheric tissue loss histologically measured after the last PET scan was significantly correlated with the decreases in CBF and CMRO2. This fully non-invasive imaging strategy may be useful for monitoring damage progression in neonatal HIE and for evaluating potential therapeutic outcomes.

Microarray-Based CD38 Peptide Probe Screening for Multiple Myeloma Imaging.

Assessing CD38 expression in vivo has become a significant element in multiple myeloma (MM) therapy, as it can be used to detect lesions and forecast the effectiveness of treatment. Accurate diagnosis requires a multifunctional, high-throughput probe screening platform to develop molecular probes for tumor-targeted multimodal imaging and treatment. Here, we investigated a microarray chip-based strategy for high-throughput screening of peptide probes for CD38. We obtained two new target peptides, CA-1 and CA-2, from a 105 peptide library with a dissociation constant (KD) of 10-7 M. The specificity and affinity of the target peptides were confirmed at the molecular and cellular levels. Peptide probes were labeled with indocyanine green (ICG) dye and 68Ga-DOTA, which were injected into a CD38-positive Ramos tumor-bearing mouse via its tail vein, and small animal fluorescence and positron emission tomography (PET) imaging showed that the peptide probes could show specific enrichment in the tumor tissue. Our study shows that a microchip-based screening of peptide probes can be used as a promising imaging tool for MM diagnosis.

Design, Synthesis, and Biological Evaluation of Small-Molecule-Based Radioligands with Improved Pharmacokinetic Properties for Imaging of Programmed Death Ligand 1.

Small molecules offer some advantages for developing positron emission tomography (PET) tracers and are therefore a promising approach for imaging and therapy monitoring of programmed death ligand 1 (PD-L1) positive tumors. Here, we report six biphenyl PD-L1 radioligands using the NODA-GA-chelator for efficient copper-64 complexation. These radioligands contain varying numbers of sulfonic and/or phosphonic acid groups, serving as hydrophilizing units to lower the log D7.4 value down to -4.28. The binding affinities of compounds were evaluated using saturation binding and a real-time binding assay, with a highest binding affinity of 21 nM. Small-animal PET imaging revealed vastly different pharmacokinetic profiles depending on the quantity and type of hydrophilizing units. Of the investigated radioligands, [64Cu]Cu-3 showed the most favorable kinetics in vitro. This was also found in vivo, with a predominantly renal clearance and a specific uptake in the PD-L1-overexpressing tumor. With further modifications, this compound could be a promising candidate for the imaging of PD-L1 in the clinical setting.

Design study of a novel geometrical arrangement for an in-beam small animal positron emission tomography scanner

Objective. We designed a geometrical solution for a small animal in-beam positron emission tomography (PET) scanner to be used in the project SIRMIO (Small animal proton irradiator for research in molecular image-guided radiation-oncology). The system is based on 56 scintillator blocks of pixelated LYSO crystals. The crystals are arranged providing a pyramidal-step shape to optimize the geometrical coverage in a spherical configuration. Approach. Different arrangements have been simulated and compared in terms of spatial resolution and sensitivity. The chosen setup enables us to reach a good trade-off between a solid angle coverage and sufficient available space for the integration of additional components of the first design prototype of the SIRMIO platform. The possibility of moving the mouse holder inside the PET scanner furthermore allows for achieving the optimum placement of the irradiation area for all the possible tumor positions in the body of the mouse. The work also includes a study of the scintillator material where LYSO and GAGG are compared with a focus on the random coincidence noise due to the natural radioactivity of Lutetium in LYSO, justifying the choice of LYSO for the development of the final system. Main results. The best imaging performance can be achieved with a sub-millimeter spatial resolution and sensitivity of 10% in the center of the scanner, as verified in thorough simulations of point sources. The simulation of realistic irradiation scenarios of proton beams in PMMA targets with/without air gaps indicates the ability of the proposed PET system to detect range shifts down to 0.2 mm. Significance. The presented results support the choice of the identified optimal design for a novel spherical in-beam PET scanner which is currently under commissioning for application to small animal proton and light ion irradiation, and which might find also application, e.g. for biological image-guidance in x-ray irradiation.

Synthesis and Biological Evaluation of Enantiomerically Pure (R)- and (S)-[18F]OF-NB1 for Imaging the GluN2B Subunit-Containing NMDA Receptors.

GluN2B subunit-containing N-methyl-d-aspartate (NMDA) receptors have been implicated in various neurological disorders. Nonetheless, a validated fluorine-18 labeled positron emission tomography (PET) ligand for GluN2B imaging in the living human brain is currently lacking. The aim of this study was to develop a novel synthetic approach that allows an enantiomerically pure radiosynthesis of the previously reported PET radioligands (R)-[18F]OF-NB1 and (S)-[18F]OF-NB1 as well as to assess their in vitro and in vivo performance characteristics for imaging the GluN2B subunit-containing NMDA receptor in rodents. A novel synthetic approach was successfully developed, which allows for the enantiomerically pure radiosynthesis of (R)-[18F]OF-NB1 and (S)-[18F]OF-NB1 and the translation of the probe to the clinic. While both enantiomers were selective over sigma2 receptors in vitro and in vivo, (R)-[18F]OF-NB1 showed superior GluN2B subunit specificity by in vitro autoradiography and higher volumes of distribution in the rodent brain by small animal PET studies.

Fibroblast Activation Protein–Targeted PET/CT With Al18F-NODA-FAPI-04 for In Vivo Imaging of Tendon Healing in Rat Achilles Tendon Injury Models

Background: Fibroblast activation protein (FAP) has shown high expression in inflammatory responses and fibrosis. Hypothesis: We speculated that FAP could serve as a diagnostic and monitoring target in the tendon healing process. Study Design: Controlled laboratory study. Methods: A total of 72 Sprague-Dawley rats were randomly divided into a tendon crush group and a half-partial tendon laceration group. Four rats in each group were injected with radiotracers weekly for 4 weeks after surgery, with aluminum fluoride–labeled 1,4,7-triazacyclononane-N,N′,N″-triacetic acid–conjugated FAP inhibitor (Al18F-NODA-FAPI-04) administered on the first day of each week and 18F-fludeoxyglucose (18F-FDG) on the next day. Small animal positron emission tomography (PET) imaging was performed, and tendon tissue was collected for pathology and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis each week after surgery. Results: One week after surgery, both radiotracers showed signal concentration at the lesion site, which was the highest radioactive uptake observed during 4 weeks postoperatively, consistent with the severity of the lesion. Consistent trends were observed for inflammatory cytokines during qRT-PCR analysis. Additionally, Al18F-NODA-FAPI-04 PET exhibited a more precise lesion pattern, attributed to its high specificity for naive fibroblasts when referring to histological findings. Over time, the uptake of both radiotracers at the injury site gradually decreased, with 18F-FDG experiencing a more rapid decrease than Al18F-NODA-FAPI-04. In the fourth week after surgery, the maximum standardized uptake values of Al18F-NODA-FAPI-04 in the injured lesion almost reverted to the baseline levels, indicating a substantial decrease in naive fibroblasts and inflammatory cells and a reduction in inflammation and fibrosis, especially compared with the first week. Corresponding trends were also revealed in pathological and qRT-PCR results. Conclusion: Our findings suggest that inflammation is a prominent feature during the early stage of tendon injury. Al18F-NODA-FAPI-04 PET allows accurate localization and provides detailed morphological imaging, enabling continuous monitoring of the healing progress and assessment of injury severity.

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 mm3 crystals, 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.

3D-printed dual holder system for simultaneous rat PET scanning: design and influence on quantification

BackgroundThe low throughout of small animal positron emission tomography (PET) images acquisitions represents a substantial limitation. The aims of this study were (i) to design a low-cost support for simultaneous dynamic PET scanning of two lying rats and (ii) to study its impact on brain image quantification.ResultsAccuracy of concentration measurement was 5.5% for one phantom in the field of view, and 5.7% for two phantoms measured simultaneously. Ratio concentration between phantoms showed an error of 6.7% ± 5.1% for Solo upper position, 6.7% ± 3.7% for Solo lower position, 5.9% ± 4.3% for Duo upper position, and 7.4% ± 6% for Duo lower position 6.7% for separated measures, and 6.6% for simultaneous measures.In vivo distribution profiles showed no difference between solo and duo uptakes. Region of Interest quantification in the whole brain showed 4.4% variability solo and 3.5% duo. The quantified test–retest bias was 8% in solo and 5% in duo, and the Intraclass Correlation Coefficient was comparable in solo and duo (0.969 vs. 0.966).ConclusionsOur results showed that simultaneous scans of two rats in INVEON do not affect quantification. The dual support system will allow us to reduce protocol costs and duration.

Automated Synthesis and Preclinical Evaluation of Optimized Integrin α6-Targeted Positron Emission Tomography Imaging of Pancreatic Cancer.

Integrin α6 has been considered a promising biomarker, is overexpressed in many tumors, and plays a vital role in tumor formation, recurrence, and metastasis. In this study, we identified a novel high-affinity integrin α6-targeted peptide named RD2 (Arg-Trp-Tyr-Asp-PEG4)2-Lys-Lys and developed a 18F-radiolabeled peptide tracer ([18F]-AlF-NOTA-RD2) and evaluated its potential application in positron emission tomography (PET) imaging of pancreatic cancer. [18F]-AlF-NOTA-RD2 was produced using GMP (Good Manufacturing Practice of Medical Products)-compliant automatic radiosynthesis on a single GE FASTLab2 cassette-type synthesis module. The stability of [18F]-AlF-NOTA-RD2 was analyzed in phosphate-buffered saline (PBS) and fetal bovine serum (FBS). The cell uptake assay of the tracer was assessed using PANC-1 cells. In addition, small-animal PET imaging and biodistribution studies of [18F]-AlF-NOTA-RD2 were performed in pancreatic cancer subcutaneous tumor-bearing mice. The PET tracer [18F]-AlF-NOTA-RD2 was obtained with a radiochemical yield of 23.7 ± 4.7%, radiochemical purity of >99%, and molar activity of 165.7 ± 59.1 GBq/μmol. [18F]-AlF-NOTA-RD2 exhibited good in vitro stability in PBS and FBS. LogP octanol water value for the tracer was -2.28 ± 0.05 (n = 3). The binding affinity of RD2 to the integrin α6 protein (Kd = 0.13 ± 3.65 μM, n = 3) was significantly higher than that of the RWY (CRWYDENAC) (Kd = 6.97 ± 1.44 μM, n = 3). Small-animal PET imaging and biodistribution also revealed that [18F]-AlF-NOTA-RD2 displayed rapid and good tumor uptake and lower liver background uptake in PANC-1 tumor-bearing mice. [18F]-AlF-NOTA-RD2 showed significant radioactivity accumulation in tumors and was successfully blocked by NOTA-RD2. Compared with [18F]-FDG, [18F]-AlF-NOTA-RD2 PET imaging and biodistribution studies in PANC-1 xenograft tumor-bearing mice confirmed a good tumor-to-muscle ratio (8.69 ± 2.03 vs 1.41 ± 0.23, respectively) at 0.5 h and (2.99 ± 3.02 vs 1.43 ± 0.17, respectively) at 1 h post injection. Autoradiography of human pancreatic cancer tumor tissues further confirmed high accumulation of [18F]-AlF-NOTA-RD2. In summary, we developed an optimized integrin α6-targeted imaging tracer and obtained high radioactivity products with a cassette-type synthesis module; moreover, the tracer exhibited good binding affinity with integrin α6 and good target specificity for PANC-1 cells in xenograft pancreatic tumor-bearing mice, demonstrating its promising application as a noninvasive PET radiotracer of integrin α6 expression in pancreatic cancer.

Prototype of a digitizer module based on multicycle-encoding FPGA ADC for a small animal PET

Current research in small animal positron emission tomography (PET) scanners focus on obtaining better spatial resolution and higher sensitivity. These enhancements of scanner performance result in a corresponding increase in the complexity of the electronics, which usually manifests through an increase in the number of electronics channels. Analog-to-digital converters (ADCs) implemented in field programmable gate arrays (FPGAs) are an effective way to simplify electronics complexity. In this paper, a resource-saving multicycle-encoding structure of an FPGA-based ADC with automated calibration is proposed, which achieves a sampling rate of 250 Msps. A digitizer module prototype containing 64 charge measurement channels based on the FPGA ADC is designed using a Kintex-7 FPGA. The effective number of bits (ENOB) achieved using the FPGA ADC is 4.26 bits under a 10.0555 MHz sine wave input. The charge measurement resolution of each channel is better than 5‰ full width half maximum under a 0.8 V signal input and 3% under inputs in the range 0.1 V to 1.2 V. The integral nonlinearity of each channel is within ± 1%.

Background reduction in PET by double Compton scattering of quantum entangled annihilation photons

The reduction of background events, such as random and scatter events, can improve positron emission tomography (PET) images quantitatively. The quantum entanglement property of annihilation photons has been theoretically studied and experimentally validated. Recently, simulation studies on PET image reconstruction using the quantum entanglement property of annihilation photons and studies on the measurement of entanglement and polarization properties with scintillation crystal arrays demonstrated that PET images with less background can be achieved. This study utilized the quantum entanglement property of annihilation photons in a typical PET system with block detectors. A data acquisition method for quantum entanglement PET (QEPET) and system response modelling for QEPET image reconstruction were proposed and implemented. An experimental study was conducted using a small animal PET system composed of Ce:GAGG scintillation crystals whose dimensions are 2.5 × 2.5 × 4mm3. The diameter of the system was 79.3 mm. Signals from all individual crystals were processed parallelly and independently; thus, Compton scatter and absorption crystals within a module were obtained directly. The 28 MBq experiment result revealed the random background ratio of QEPET was approximately 20% lower than that of PET and the count rate of QEPET was approximately 0.1% that of PET. Evaluation on reconstructed images from the 28 MBq experiment revealed that the signal-to-background ratio of QEPET was approximately two times better than that of PET while the signal-to-noise ratio of QEPET was about 77% of that of PET. The method proposed in this study is expected to improve PET images with high background, such as those with a high activity and high background gamma rays and improve range verification in proton therapy.

Residual 3D convolutional neural network to enhance sinograms from small-animal positron emission tomography images

Positron emission tomography (PET) has been widely used in nuclear medicine to diagnose cancer. PET images suffer from degradation because of the scanner's physical limitations, the radiotracer's reduced dose, and the acquisition time. In this work, we propose a residual three-dimensional (3D) and convolutional neural network (CNN) to enhance sinograms acquired from a small-animal PET scanner. The network comprises three convolutional layers created with 3D filters of sizes 9, 5, and 5, respectively. For training, we extracted 15250 3D patches from low- and high-count sinograms to build the low- and high-resolution pairs. After training and prediction, the image was reconstructed from the enhanced sinogram using the ordered subset expectation maximization (OSEM) algorithm. The results revealed that the proposed network improves the spillover ratio by up to 4.5% and the uniformity by 55% compared to the U-Net. The NEMA phantom data were obtained in a simulation environment. The network was tested on acquired real data from a mouse. The reconstructed images and the profiles of maximum intensity projection show that the proposed method visually yields sharper images.2023 Elsevier Ltd. All rights reserved.

Collimator design for gamma-ray cascade angular correlations in medical imaging

In recent decades, Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) have become workhorses of molecular imaging. The main drawback of these modalities is that they resort to statistical methods of image reconstruction, as the location of the individual nuclei emitting radiation is not accessible. To remedy this situation, we embarked on a project to introduce a new modality of nuclear medical imaging which exploits the non-collinear angular correlations of nuclear gamma-ray cascades subsequent to beta decays. This modality, if effective, determines the location of each decay nucleus. We have retrofitted the small animal PET assembly of RIKEN-Kobe (Japan) with tungsten+PLA (polylactic acid) collimators. The chosen material is inexpensive, amenable to three-dimensional (3D) printing, and has good photon attenuation properties. We included the collimator geometry in GATE (Geant4 Application for Tomographic Emission) simulations and developed algorithms for image reconstruction with medical isotope candidates viz., 111In and 43K. Our preliminary simulations show that data acquisition with a 2 MBq source for 900 s is sufficient to reproduce the source geometry with high resolution. This report summarizes our progress to date and the plans for the near future.

A CNN-based four-layer DOI encoding detector using LYSO and BGO scintillators for small animal PET imaging

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 mm3 LYSO crystals, a 24 × 24 array of 0.99 × 0.99 × 6 mm3 BGO crystals, a 16 × 16 array of 1.53 × 1.53 × 6 mm3 LYSO crystals and a 16 × 16 array of 1.53 × 1.53 × 6 mm3 BGO 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.