Small Animal PET Scanner Research Articles

Performance evaluation of a small-animal PET scanner with 213 mm axis using NEMA NU 4-2008.

Long-axis positron emission tomography (PET) has emerged as one of the recent research directions in PET due to its ability to significantly enhance sensitivity and counting performance for low-dose imaging, rapid imaging, and whole-body dynamicimaging. The PET system presented in this study is a long-axis animal PET based on lutetium-yttrium orthosilicate and silicon photomultiplier, designed for whole-body imaging in rats. It features a diameter of 143 mm and an axial length of 213.3 mm. This study evaluated the performance of this PET system in accordance with the National Electrical Manufacturers Association (NEMA) NU 4-2008standards. The performance evaluation was conducted according to the NEMA NU 4-2008 standards in terms of spatial resolution, sensitivity, counting rate performance, scatter fraction (SF) and image quality. In addition, a rat imaging study was conducted to assess the imaging capability of this PETsystem. The average energy resolution of the PET system was 12.87%, the average coincidence timing resolution was 751 ps. The FWHM of spatial resolution reconstructed by filtered back projection and 3D-OSEM-PSF algorithm at 5 mm radial offset from the axial center were 1.65 and 0.88 mm. The peak absolute sensitivity measured by a point source at the center of the field of view was evaluated as 6.71% (361-661keV) and 10.31% (250-750 keV). For the mouse-like phantom, the SF was 11.0% and the peak noise equivalent counting rate (NECR) was 1193 kcps at 94.2 MBq (2.54 mCi). For the rat-like phantom, the SF was 26.8% and the NECR was 682.5 kcps at 78.6 MBq (2.12 mCi). The performance measurement results demonstrate that this PET system exhibits high sensitivity and count rate performance, making it potential for high-quality whole-body dynamic imaging ofrats.

Towards multicenter β-amyloid PET imaging in mouse models: A triple scanner head-to-head comparison

Aimβ-amyloid (Aβ) small animal PET facilitates quantification of fibrillar amyloidosis in Alzheimer's disease (AD) mouse models. Thus, the methodology is receiving growing interest as a monitoring tool in preclinical drug trials. In this regard, harmonization of data from different scanners at multiple sites would allow the establishment large collaborative cohorts and may facilitate efficacy comparison of different treatments. Therefore, we objected to determine the level of agreement of Aβ-PET quantification by a head-to-head comparison of three different state-of-the-art small animal PET scanners, which could help pave the way for future multicenter studies. MethodsWithin a timeframe of 5 ± 2 weeks, transgenic APPPS1 (n = 9) and wild-type (WT) (n = 8) mice (age range: 13–16 months) were examined three times by Aβ-PET ([18F]florbetaben) using a Siemens Inveon DPET, a MedisonanoScan PET/MR, and a MedisonanoScan PET/CT with harmonized reconstruction protocols. Cortex-to-white-matter 30–60 min p.i. standardized uptake value ratios (SUVRCTX/WM) were calculated to compare binding differences, effect sizes (Cohen's d) and z-score values of APPPS1 relative to WT mice. Correlation coefficients (Pearson's r) were calculated for the agreement of individual SUVR between different scanners. Voxel-wise analysis was used to determine the agreement of spatial pathology patterns. For validation of PET imaging against the histological gold standard, individual SUVR values were subject to a correlation analysis with area occupancy of methoxy‑X04 staining. ResultsAll three small animal PET scanners yielded comparable group differences between APPPS1 and WT mice (∆PET=20.4 % ± 2.9 %, ∆PET/MR=18.4 % ± 4.5 %, ∆PET/CT=18.1 % ± 3.3 %). Voxel-wise analysis confirmed a high degree of congruency of the spatial pattern (Dice coefficient (DC)PETvs.PET/MR=83.0 %, DCPETvs.PET/CT=69.3 %, DCPET/MRvs.PET/CT=81.9 %). Differences in the group level variance of the three scanners resulted in divergent z-scores (zPET=11.5 ± 1.6; zPET/MR=5.3 ± 1.3; zPET/CT=3.4 ± 0.6) and effect sizes (dPET=8.5, dPET/MR=4.5, dPET/CT=4.1). However, correlations at the individual mouse level were still strong between scanners (rPETvs.PET/MR=0.96, rPETvs.PET/CT=0.91, rPET/MRvs.PET/CT=0.87; all p ≤ 0.0001). Methoxy-X04 staining exhibited a significant correlation across all three PET machines combined (r = 0.76, p < 0.0001) but also at individual level (PET: r = 0.81, p = 0.026; PET/MR: r = 0.89, p = 0.0074; PET/CT: r = 0.93, p = 0.0028). ConclusionsOur comparison of standardized small animal Aβ-PET acquired by three different scanners substantiates the possibility of moving towards a multicentric approach in preclinical AD research. The alignment of image acquisition and analysis methods achieved good overall comparability between data sets. Nevertheless, differences in variance of sensitivity and specificity of different scanners may limit data interpretation at the individual mouse level and deserves methodological optimization.

Exploring the gamma counting function in PET for sample activity measurement

With the widespread availability of small animal PET scanners globally, there exists a significant opportunity to enhance their operational utility. Our research introduces a novel utilization pathway by integrating gamma-counting functionalities within PET systems. This approach leverages the shared gamma counting technology between PET systems and traditional gamma counters, enabling direct radioactivity measurement from PET-derived raw count data. We established a correlation between the raw data from all-digital PET and the radioactivity of samples, conducting experiments to assess the system's measurement capabilities. The system demonstrated high accuracy and stability across a detectable range of 25.53–1900.69 kBq in single-photon mode and 19.61–1107.04 kBq in coincidence mode, with the difference between the sample activity and the linear function being no more than 5 %. Due to the multi-channel characteristic of PET detectors, our system exhibits a tenfold higher upper detection limit than that of gamma counters, without dead-time correction. This study demonstrates that all-digital PET can directly measure radioactivity, simplifying nuclear medicine procedures by integrating gamma counting within PET systems. This strategy not only reduces the need for multiple instruments but also has the potential to improve quantitative accuracy by minimizing cross-calibration errors, thereby maximizing the operational utility of existing all-digital PET scanners.

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.

Fragmentation of functional resting state brain networks in a transgenic mouse model of tau pathology: A metabolic connectivity study using [18F]FDG-PET

In a previous study, regional reductions in cerebral glucose metabolism have been demonstrated in the tauopathy mouse model rTg4510 (Endepols et al., 2022). Notably, glucose hypometabolism was present in some brain regions without co-localized synaptic degeneration measured with [18F]UCB-H. We hypothesized that in those regions hypometabolism may reflect reduced functional connectivity rather than synaptic damage. To test this hypothesis, we performed seed-based metabolic connectivity analyses using [18F]FDG-PET data in this mouse model. Eight rTg4510 mice at the age of seven months and 8 non-transgenic littermates were injected intraperitoneally with 11.1 ± 0.8 MBq [18F]FDG and spent a 35-min uptake period awake in single cages. Subsequently, they were anesthetized and measured in a small animal PET scanner for 30 min. Three seed-based connectivity analyses were performed per group. Seeds were selected for apparent mismatch between [18F]FDG and [18F]UCB-H. A seed was placed either in the medial orbitofrontal cortex, dorsal hippocampus or dorsal thalamus, and correlated with all other voxels of the brain across animals. In the control group, the emerging correlative pattern was strongly overlapping for all three seed locations, indicating a uniform fronto-thalamo-hippocampal resting state network. In contrast, rTg4510 mice showed three distinct networks with minimal overlap. Frontal and thalamic networks were greatly diminished. The hippocampus, however, formed a new network with the whole parietal cortex. We conclude that resting-state functional networks are fragmented in the brain of rTg4510 mice. Thus, hypometabolism can be explained by reduced functional connectivity of brain areas devoid of tau-related pathology, such as the thalamus.

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.

Comparative analysis of image quality parameters and spatial resolution of three Small Animal PET scanner in Brazil

This study evaluated Image Quality (IQ) parameters and spatial resolution (SR) of Triumph® LabPET systems installed in three different Brazilian preclinical molecular imaging centers. A comprehensive evaluation of the PET scanner intrinsic parameters is important to optimize the acquired images, providing more reliable qualitative and quantitative analyses. Experiments were carried out at the centers: C1 - Molecular Imaging Laboratory of the CDTN/CNEN; C2 - Laboratory of Nuclear Medicine of HCFMUSP; C3 - Preclinical Research Center of the Brain Institute at PUC-RS. IQ phantom PET images were acquired as recommended in NEMA NU 4-2008 standard. Image reconstructions were performed in each system using the same reconstruction protocol. Data was processed using PMOD® software. The IQ parameters: (i) uniformity, (ii) spill-over ratio (SOR) and (iii) recovery coefficients (RC) were evaluated and compared. For Uniformity test, the percentage standard deviations of mean activity concentration were 7.8%; 7.3% and 6.4% for Centers 1, 2 and 3 respectively. Cold chambers RSO values in the systems 1, 2 and 3 were respectively 0.16, 0.19 and 0.21 for water; 0.26; 0.28 and 0.30 for air. The RC’s for rod diameters from 1 to 5 mm ranged from 0.08 to 0.91 for the three centers. Results revealed that the three PET systems have appropriate quality parameters for pre-clinical studies, presenting values compatible with international standards. This study was able to reveals the performance of preclinical PET system of different Brazilian imaging centers and may support the standardization of a National Quality Control Program for Small Animal PET scanners.

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.

Submillimeter-Resolution PET for High-Sensitivity Mouse Brain Imaging.

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

The 100[formula omitted]PET project: A small-animal PET scanner for ultra-high resolution molecular imaging with monolithic silicon pixel detectors

Recent developments in semiconductor pixel detectors allow a new generation of positron-emission tomography (PET) scanners that, combined with advanced image reconstruction algorithms, will allow for a few hundred microns spatial resolutions. Such novel scanners will pioneer ultra-high resolution molecular imaging, a field that is expected to have an enormous impact in several medical domains, neurology among others.The University of Geneva, the École Polytechnique Fédérale de Lausanne, and the University of Lucerne, have launched the 100μPET project that aims to produce a small-animal PET scanner with ultra-high resolution. The scanner will be composed of 4 ”towers”, each containing a stack of 60 monolithic silicon pixel sensors for the direct measurement of the annihilation photons. The sensors are 270 μm thick, providing unprecedented depth-of-interaction measurement. Monte Carlo simulations were done simulating different scanner conditions, resulting in a spatial resolution down to 0.2 mm FWHM and a sensitivity of 3.2%.

Proposal of Brazilian National Program for Quality Control in the small animal PET scanners

In Brazil, currently there are six preclinical molecular imaging centers and seven different small animal PET systems in use. However, there is still no national specific legislation for research laboratories focused on preclinical molecular images, unlike clinical nuclear medicine centers. A standardization of quality control protocols is needed to harmonize the use of small animal PET scanners in the research field. Thus, the aim of this work was to propose a National Program for Quality Control (NPQC) for the preclinical PET imaging systems in Brazil. This work was based on the quality control tests performed in Molecular Image Laboratory LIM/CDTN based on NEMA NU 4-2008 as described and presented in doctoral thesis of GONTIJO, 2019. The proposal of the NQCP was based on the CNEN NN 3.05 Publication (2013) and includes fundamental tests to be adopted, if possible, in laboratory practice to corroborate the experimental data. The Quality Control Program implemented in LIM/CDTN is an innovative and unprecedented proposal in the scope of preclinical molecular imaging services in Brazil. Therefore, the LIM/CDTN Program was carried out as a pilot to evidence the applicability and viability of the NQCP using small animal PET scanners. Summarizing, this work presents a viable set of Quality Control tests and their periodicities like a proposal for standardization to harmonize the use of this imaging technology in the field of research. Therefore, a National Quality Control Program (NQCP) applied to small animal PET scanners.

Performance based on NEMA NU-4 2008 Standard of CDTN/CNEN’s Small Animal PET Scanner

This study aimed to evaluate the general performance of the preclinical PET scanner (LabPET Solo 4, GE) at CDTN/CNEN using the NEMA NU 4-2008 protocol. The performance parameters include: (i) spatial resolution; (ii) scatter fraction and counts rate performance; (iii) sensitivity and (iv) image quality. For the evaluation specific simulators and a sealed radioactive source of Sodium-22 were used. The results revealed that the NEMA-based radial spatial resolution ranged from 1.79 mm at the center of the FOV to 2.49 mm at a radial offset of 25mm. Tangential resolution ranged from 1.95mm at the center of the FOV to 3.50mm at a radial offset of 25mm. Axial resolution ranged from 1.78mm at the center of the FOV to 5.42mm at a radial offset of 25mm. Iterative image reconstruction improved the radial spatial resolution to 0.93mm at the center of the FOV. For the mouse-sized phantom, the peak noise equivalent count rate (NECR) was 37.8kcps at 85MBq whereas the peak true count rate was 169.9kcps at 125MBq with a count loss of 7.8% for the maximum rate reached at 103.3MBq. The peak of sensitivity (S) and absolute sensitivity (SA) at the center of axial field-of-view (FOV) is 5.7cps.Bq-1 and 0.63%, respectively. The overall imaging capabilities of the scanner were assessed using the NEMA image-quality phantom. The image roughness was 9.5%. Spillover rates (SORs) in air and in water were 0.26 and 0.17 respectively. The recovery coefficients (RCs) were 0.12 for the 1-mm-diameter rod and 0.91 for the 5-mm-diameter rod. The results demonstrate that CDTN/CNENsmall animal PET scanner has adequate reliability and acquired images are compatible with international quality standards for the molecular imaging research.

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

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. 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 0.4×0.4×20mm3 size. Crystal array 3 consisted of 16×16 GAGG crystals of 0.3×0.3×20mm3 size, and crystal array 4 consisted of 24×24 LYSO crystals 0.3×0.3×20mm3 in size. The crystal arrays were dual-ended readouts using 8×8 silicon photomultiplier (SiPM) arrays of 2×2mm2 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. 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 <2mm, energy resolutions of <22%, and timing resolutions of <1.6ns. All crystals of 0.4×0.4×20mm3 and 0.3×0.3×20 mm3 could be clearly resolved if the crystal array was 1mm smaller in the four sides than that in the SiPM array. High DOI resolution PET detectors were developed using both GAGG and LYSO arrays with crystal sizes of 0.3 and 0.4mm, respectively, and a length of 20mm. 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.

Assessment of the In Vivo Relationship Between Cerebral Hypometabolism, Tau Deposition, TSPO Expression, and Synaptic Density in a Tauopathy Mouse Model: a Multi-tracer PET Study

Cerebral glucose hypometabolism is a typical hallmark of Alzheimer’s disease (AD), usually associated with ongoing neurodegeneration and neuronal dysfunction. However, underlying pathological processes are not fully understood and reproducibility in animal models is not well established. The aim of the present study was to investigate the regional interrelation of glucose hypometabolism measured by [18F]FDG positron emission tomography (PET) with various molecular targets of AD pathophysiology using the PET tracers [18F]PI-2620 for tau deposition, [18F]DPA-714 for TSPO expression associated with neuroinflammation, and [18F]UCB-H for synaptic density in a transgenic tauopathy mouse model. Seven-month-old rTg4510 mice (n = 8) and non-transgenic littermates (n = 8) were examined in a small animal PET scanner with the tracers listed above. Hypometabolism was observed throughout the forebrain of rTg4510 mice. Tau pathology, increased TSPO expression, and synaptic loss were co-localized in the cortex and hippocampus and correlated with hypometabolism. In the thalamus, however, hypometabolism occurred in the absence of tau-related pathology. Thus, cerebral hypometabolism was associated with two regionally distinct forms of molecular pathology: (1) characteristic neuropathology of the Alzheimer-type including synaptic degeneration and neuroinflammation co-localized with tau deposition in the cerebral cortex, and (2) pathological changes in the thalamus in the absence of other markers of AD pathophysiology, possibly reflecting downstream or remote adaptive processes which may affect functional connectivity. Our study demonstrates the feasibility of a multitracer approach to explore complex interactions of distinct AD-pathomechanisms in vivo in a small animal model. The observations demonstrate that multiple, spatially heterogeneous pathomechanisms can contribute to hypometabolism observed in AD mouse models and they motivate future longitudinal studies as well as the investigation of possibly comparable pathomechanisms in human patients.

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

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. 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. The SIAT aPET detectors provided good flood histograms such that all but the corner crystals can be resolved even with lower energies of 250-350keV, an average energy resolution of 21.1 ± 1.9%, and an average timing resolution of 2.63 ± 0.69ns. The average spatial resolutions obtained with EWs of 250-350keV and 450-550keV are 0.68mm and 0.75mm. For EWs of 250-750keV, 350-750keV, and 450-750keV with a fixed TW of 12ns, 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 4ns, 8ns,12ns, and 20ns with a fixed EW of 350-750keV, 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 0.8mm 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. 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.

Noninvasive estimation of human radiation dosimetry of 18F-FDG by whole-body small animal PET imaging in rats

PurposeSmall animal PET provides the biodistribution of administrated radiotracer in vivo and have a potential to contribute on dosimetry study. The aim of this study is to investigate the effect of region-of-interest (ROI)-delineation in whole-body rat PET image toward non-invasive estimation of human dosimetry of 18F-FDG. MethodAfter administration of 18F-FDG (averaged 11.7 MBq), 3.5-h PET and 20-min CT scans were sequentially performed for three rats by Clairvivo PET/CT system. Seven source organs, and the remainder of the body, were studied to extrapolate %ID(t) and estimate time-integrated activity coefficients [kBq-h/MBq] in human. The mean absorbed dose in each target organ and the effective dose were estimated by MIRD method. Effects of ROI-definitions on both extrapolated %ID(t) in human and estimated doses were also investigated by using (i) small ROIs of high uptake region and (ii) whole organ ROIs. ResultsAveraged effective doses of 18F-FDG in human by using high-uptake and whole-organ ROIs were 27.8 ± 6.54 and 19.3 ± 2.72 μSv/MBq, respectively. ConclusionThe use of small animal PET scanner, which allows repeatedly PET scans, have a potential to contribute on the reduction of the number of experimental animals. However, the ways of ROI drawing influences on the estimated effective dose and safe-side ROI definition may be preferred.

Influence of image reconstruction protocols on the image quality of a small animal PET scanner using 18F and 11C

The small animal positron emission tomography (PET) scanner from Molecular Imaging Laboratory (LIM/CDTN) is dedicated to pre-clinical studies on new 18F and 11C-based radiopharmaceuticals and to development of novel applications for well-known radiopharmaceuticals. Thus, quality control tests recommended by the publication NEMA NU 4-2008 are routinely carried out to ensure the proper performance of PET scanner. The aim of this work was to evaluate the influence of image reconstruction protocols on the image quality, accuracy of attenuation and scatter corrections parameters for 18F and 11C PET images. PET images of the image quality phantom filed with 18F-FDG or 11C-PK1122 were acquired and then reconstructed using different reconstruction protocols. The reconstruction variables evaluated were the algorithms (FBP, MLEM-3D, OSEM-3D), the resolution mode (high/standard) and the number of iterations (10 to 150). Uniformity, spill-over ratio (SOR) and recovery coefficients (RC) tests were performed for each reconstructed image according NEMA NU 4-2008. PMOD software was used for image analysis. FBP based protocol generated noisier images compared to iterative algorithms (MLEM-3D or OSEM-3D) based protocols. The increase in the number of iterations resulted in higher standard deviation of the analyzed parameters for all reconstructed images. MLEM-3D and OSEM-3D based protocols generates similar results when number of iterations and resolution mode were identical. SOR and RC mean values remained stable when the number of iterations ranged from 40 to 150. This study allowed the evaluation of different image reconstruction protocols on important parameters of 18F and 11C PET image quality. Additionally, standard image reconstruction protocols to be adopted in LIM/CDTN laboratorial routine for 18F and 11C images reconstruction in preclinical studies were defined.

Development of dual-ended depth-of-interaction detectors using laser-induced crystals for small animal PET systems

Sensitivity and spatial resolution of positron emission tomography (PET) scanners can be improved by using thicker scintillation crystals with depth-of-interaction (DOI) encoding. Subsurface laser engraving (SSLE) can be used to segment crystals of a scintillation detector in order to fabricate a DOI detector. We previously applied SSLE to crystal bars of 3 × 3 × 20 mm3 and 1.5 × 1.5 × 20 mm3 and developed two dual-ended detectors with DOI segments of 3 mm and 1.5 mm, respectively. To further improve the DOI resolution, our SSLE detector design can be used with smaller pitch crystal bars, making them excellent detector candidates for small animal PET scanners with submillimetre resolution. In the present study, three small crystal bars of 1 × 1 × 20 mm3, 2 × 1 × 20 mm3, and 2 × 1 × 40 mm3 were laser engraved to 12, 20 and 40 segments, respectively, by applying SSLE in their height directions. The segmented crystal bars were characterised in three prototype detector arrangements. First, the 1 × 1 × 20 mm3 crystal bars were characterised in an 8 × 8 crystal array designed for DOI encoding along crystal height in a conventional small animal PET design. Second, a 4 × 8 crystal array of 2 × 1 × 20 mm3 crystal bars was characterised for using the DOI information for crystal interaction positioning along the axial axis of a small animal PET scanner. Finally, the third part of the study was performed on a single 2 × 1 × 40 mm3 crystal bar with 40 segments to investigate the feasibility of DOI estimation in longer crystals for application in a system with extended axial length. We evaluated the capability of segment identification and energy resolution of theses detectors. The 3D position maps of the detectors were obtained using the Anger-type calculation and the crystal identification performance was evaluated for each detector. Clear segment separation was obtained for the crystal arrays with 12 (segment pitch of 1.67 mm) and 20 (segment pitch of 1 mm) segments. Mean energy resolutions of 8.8% ± 0.4% and 9.6% ± 0.8% at 511 keV were obtained for the segments in the central regions of the 8 × 8 array with 12 segments and the 4 × 8 array with 20 segments, respectively. Clear segment identification was found to be difficult for the detector with 40 segments, especially for the segments at the middle of the crystal. Energy and interaction positioning characterisation results suggest that both prototype detectors with 12 and 20 segments are well suited for small animal PET scanners with high spatial resolution.

Spatial resolution of a preclinical PET tomograph

Positron emission tomography (PET) is an important molecular image modality and its application on preclinical research has increased during last decades. Thus, in laboratory practice, it is important to implement a quality control of the equipment, since intrinsic factors influence the image quality. The objective of this work was to perform and implement spatial resolution tests for the small animal PET scanner of the Molecular Imaging Laboratory, LIM/CDTN. Empirically, spatial resolution of a PET scanner can be determined from the measurement of point or linear sources and FWHM (full width half maximum) analysis of the respective linear profiles. In this work, a point source of 22Na and a hot rod style phantom filled with 18F-FDG solution were used. Acquisition and reconstruction of images were performed with the LabPET 1.12.1 software, provided by the equipment manufacturer. Image reconstruction parameters followed the LIM standard protocol: MLEM-3D algorithm, 20 iterations, no high resolution mode, no attenuation or scatter corrections, no post-filtering. PeakFit® and Amide softwares were used to perform images post-processing. The results indicate that the scanner has an adequate spatial resolution and its value is compatible with values reported in international studies performed on similar equipments.

A staggered 3-layer DOI PET detector using BaSO4 reflector for enhanced crystal identification and inter-crystal scattering event discrimination capability

The spatial resolution of small animal positron emission tomography (PET) scanners can be improved by the use of crystals with fine pitch and rejection of inter-crystal scattering (ICS) events, which leads to a better quantification of radiopharmaceuticals. On the other hand, depth-of-interaction (DOI) information is essential to preserve the spatial resolution at the PET field-of-view (FOV) periphery while keeping the sensitivity. In this study we proposed a novel staggered 3-layer DOI detector using BaSO4 reflector material for an enhanced crystal identification performance as well as ICS event rejection capability over those of ESR reflector based DOI detectors. The proposed staggered 3-layer DOI detector had 3-layer staggered LYSO crystal arrays (crystal pitch = 1 mm), an acrylic light guide, and a 4 × 4 SiPM array. The 16 SiPM anode signals were read out by using a resistive network to encode the crystal position and energy information while the timing signal was extracted from the common cathode. The crystal map quality was substantially enhanced by using the BaSO4 reflector material as compared to that of the ESR reflector due to the low optical crosstalk between the LYSO crystals. The ICS events can be rejected with BaSO4 by using simple pulse height discrimination thanks to the light collection efficiency difference that depends on the crystal layers. As a result, the total number of events was decreased around 26% with BaSO4 as compared to that of ESR. The overall energy resolution and coincidence timing resolution with BaSO4 were 19.7 ± 5.6% and 591 ± 160 ps, respectively which were significantly worse than 10.9 ± 2.2% and 308 ± 23 ps values of ESR because of the relatively low light collection efficiency with BaSO4 (1057 ± 308 ADC) compared to that of ESR (1808 ± 118 ADC). In conclusion, we found the proposed staggered 3-layer DOI detector using the BaSO4 reflector material with ICS event rejection capability can be a cost-effective solution for realizing high resolution and highly sensitive small animal PET scanners while minimizing the complexity of the SiPM readout circuit.