Performance evaluation of a high-sensitivity large-aperture small-animal PET scanner: ClairvivoPET

OBJECTIVE: In this study, we evaluated the performance of a newly commercialized small-animal positron emission tomography (PET) scanner, ClairvivoPET, which provides significant advantages in spatial resolution, sensitivity, and quantitative accuracy. METHODS: This scanner consists of depth of interaction detector modules with a large axial extent of 151 mm and an external (137)Cs source for attenuation correction. Physical performances, resolution, sensitivity, scatter fraction (SF), counting rate including noise equivalent count (NEC) rate, quantitative accuracy versus activity strength, and transmission accuracy, were measured and evaluated. Animal studies were also performed. RESULTS: Transaxial spatial resolution, measured with a capillary tube, was 1.54 mm at the center and 2.93 mm at a radial offset of 40 mm. The absolute sensitivity was 8.2% at the center, and SFs for mouse-and rat-sized phantoms were 10.7% and 24.2%, respectively. Peak NEC rates for mouse-and rat-sized uniform cylindrical phantoms were 328 kcps at 173 kBq/ml and 119 kcps at 49 kBq/ml, respectively. The quantitative stability of emission counts against activity strength was within 2% over 5 half-lives, ranging from 0.6 MBq to 30 MBq. Transmission measurement based on segmented attenuation correction allowed 6-min and 10-min scans for mouse-and rat-sized cylindrical phantoms, respectively. Rat imaging injected with (18)F-NaF resulted in visibility of fine bone structures, and mouse imaging injected with (18)F-D-fluoromethyl tyrosine demonstrated the feasibility of using this system to obtain simultaneous time activity curves from separate regions, such as for the heart and tumors. CONCLUSIONS: ClairvivoPET is well suited to quantitative imaging even with short scan times, and will provide a number of advantages in new drug development and for kinetic measurement in molecular imaging.     

Preliminary study on potential of the jPET-D4 human brain scanner for small animal imaging

Objective  One trend in positron emission tomography (PET) instrumentation over the last decade has been the development of scanners dedicated to small animals such as rats and mice. Thicker crystals, which are necessary to obtain higher sensitivity, result in degraded spatial resolution in the peripheral field-of-view (FOV) owing to the parallax error. On the other hand, we are developing the jPET-D4, which is a dedicated human brain PET scanner that has a capability for depth-of-interaction (DOI) measurement. Although its crystal width is about twice that of commercially available small animal PET scanners, we expect the jPET-D4 to have a potential for small animal imaging by making full use of the DOI information. In this article, we investigate the jPET-D4’s potential for small animal imaging by comparing it with the microPET Focus220, a state-of-the-art PET scanner dedicated to small animals. Methods  The jPET-D4 uses four-layered GSO crystals measuring 2.9 mm × 2.9 mm × 7.5 mm, whereas the microPET Focus220 uses a single layer of LSO crystals measuring 1.5 mm × 1.5 mm × 10.0 mm. First, the absolute sensitivity, counting rate performance and spatial resolution of both scanners were measured. Next a small hot-rod phantom was used to compare their imaging performance. Finally, a rat model with breast tumors was imaged using the jPET-D4. Results  Thanks to the thicker crystals and the longer axial FOV, the jPET-D4 had more than four times higher sensitivity than the microPET Focus220. The noise equivalent counting-rate performance of the jPETD4 reached 1,024 kcps for a rat-size phantom, whereas that of the microPET Focus220 reached only 165 kcps. At the center of the FOV, the resolution was 1.7 mm for the microPET Focus220, whereas it was 3.2 mm for the jPET-D4. On the other hand, the difference of resolution became smaller at the off-center position because the radial resolution degraded faster for the microPET Focus220. The results of phantom imaging showed that the jPET-D4 was comparable to the microPET Focus220 at the off-center position even as the microPET Focus220 outperformed the jPET-D4 except for the peripheral FOV. Conclusions  The jPET-D4 human brain PET scanner, which was designed to achieve not only high resolution but also high sensitivity by measuring DOI information, was proven to have a potential for small animal imaging.     

Multi-tracer small animal PET imaging of the tumour response to the novel pan-Erb-B inhibitor CI-1033

Purpose This study was designed as “proof of concept” for a drug development model utilising multi-tracer serial small animal PET imaging to characterise tumour responses to molecularly targeted therapy. Methods Mice bearing subcutaneous A431 human squamous carcinoma xenografts (n=6–8) were treated with the pan-Erb-B inhibitor CI-1033 or vehicle and imaged serially (days 0, 3 and 6 or 7) with [¹⁸F]fluorodeoxyglucose, [¹⁸F]fluoro-L-thymidine, [¹⁸F]fluoro-azoazomycinarabinoside or [¹⁸F]fluoromisonidazole. Separate cohorts (n=3) were treated identically and tumours were assessed ex vivo for markers of glucose metabolism, proliferation and hypoxia. Results During the study period, mean uptake of all PET tracers generally increased for control tumours compared to baseline. In contrast, tracer uptake into CI-1033-treated tumours decreased by 20–60% during treatment. Expression of the glucose transporter Glut-1 and cell cycle markers was unchanged or increased in control tumours and generally decreased with CI-1033 treatment, compared to baseline. Thymidine kinase activity was reduced in all tumours compared to baseline at day 3 but was sevenfold higher in control versus CI-1033-treated tumours by day 6 of treatment. Uptake of the hypoxia marker pimonidazole was stable in control tumours but was severely reduced following 7 days of CI-1033 treatment. Conclusion CI-1033 treatment significantly affects tumour metabolism, proliferation and hypoxia as determined by PET. The PET findings correlated well with ex vivo biomarkers for each of the cellular processes studied. These results confirm the utility of small animal PET for evaluation of the effectiveness of molecularly targeted therapies and simultaneously definition of specific cellular processes involved in the therapeutic response. The first two authors contributed equally to the results presented in this report.     

Dynamic <Superscript>18</Superscript>F-fluoride small animal PET to noninvasively assess renal function in rats

Purpose

Renal function can be quantified by both laboratory and scintigraphic methods. In the case of small animal diagnostics, scintigraphic image-based methods are ideal since they can assess split renal function, work noninvasively, and can be repeated. The aim of this study is to validate a ¹⁸F-PET-based method to quantify renal function in rats.

Materials and methods

Fluoride clearance was calculated from a dynamic whole body listmode acquisition of 60 min length in a small animal PET scanner following an i.v. injection of 15 MBq ¹⁸F-fluoride. Volumes of interest (VOIs) were placed in the left ventricle and the bladder as well as traced around the kidney contours. The respective time–activity curves (TAC) were calculated. The renal ¹⁸F-clearance was calculated by the ratio of the total renal excreted activity (bladder VOI) and the integral of the blood TAC. PET-derived renal function was validated by intraindividual measurements of creatinine clearance (n?=?23), urea clearance (n?=?23), and tubular excretion rate (TER-MAG3). The split renal function was derived from the injection of the clinically available radionuclide ^99mTc-mercaptotriglycine by blood sampling and planar renography (n?=?8).

Results

In all animals studied, PET revealed high-quality TACs. PET-derived renal fluoride clearance was linearly correlated with intraindividual laboratory measures (PET vs. creatinine: r?=?0.78; PET vs. urea: r?=?0.73; PET vs. TER-MAG3: r?=?0.73). Split function was comparable (¹⁸F-PET vs. MAG3-renography: r?=?0.98). PET-derived measures were highly reproducible.

Conclusions

¹⁸F-PET is able to noninvasively assess renal function in rats and provides a significant potential for serial studies in different experimental scenarios.

     

Hybrid image and blood sampling input function for quantification of small animal dynamic PET data

We describe and validate a hybrid image and blood sampling (HIBS) method to derive the input function for quantification of microPET mice data. The HIBS algorithm derives the peak of the input function from the image, which is corrected for recovery, while the tail is derived from 5 to 6 optimally placed blood sampling points. A Bezier interpolation algorithm is used to link the rightmost image peak data point to the leftmost blood sampling point. To assess the performance of HIBS, 4 mice underwent 60-min microPET imaging sessions following a 0.40–0.50-mCi bolus administration of ¹⁸FDG. In total, 21 blood samples (blood-sampled plasma time–activity curve, bsPTAC) were obtained throughout the imaging session to compare against the proposed HIBS method. MicroPET images were reconstructed using filtered back projection with a zoom of 2.75 on the heart. Volumetric regions of interest (ROIs) were composed by drawing circular ROIs 3 pixels in diameter on 3–4 transverse planes of the left ventricle. Performance was characterized by kinetic simulations in terms of bias in parameter estimates when bsPTAC and HIBS are used as input functions. The peak of the bsPTAC curve was distorted in comparison to the HIBS-derived curve due to temporal limitations and delay in blood sampling, which affected the rates of bidirectional exchange between plasma and tissue. The results highlight limitations in using bsPTAC. The HIBS method, however, yields consistent results, and thus, is a substitute for bsPTAC.     

FDG small animal PET permits early detection of malignant cells in a xenograft murine model

Purpose The administration of new anticancer drugs in animal models is the first step from in vitro to in vivo pre-clinical protocols. At this stage it is crucial to ensure that cells are in the logarithmic phase of growth and to avoid vascular impairment, which can cause inhomogeneous distribution of the drug within the tumour and thus lead to bias in the final analysis of efficacy. In subcutaneous xenograft murine models, positivity for cancer is visually recognisable 2–3 weeks after inoculation, when a certain amount of necrosis is usually already present. The aim of this study was to evaluate the accuracy of FDG small animal PET for the early detection of malignant masses in a xenograft murine model of human rhabdomyosarcoma. A second goal was to analyse the metabolic behaviour of this xenograft tumour over time. Methods We studied 23 nude mice, in which 7 × 10⁶ rhabdomyosarcoma cells (RH-30 cell line) were injected in the dorsal subcutaneous tissues. Each animal underwent four FDG PET scans (GE, eXplore Vista DR) under gas anaesthesia. The animals were studied 2, 5, 14 and 20 days after inoculation. We administered 20 MBq of FDG via the tail vein. Uptake time was 60 min, and acquisition time, 20 min. Images were reconstructed with OSEM 2D iterative reconstruction and the target to background ratio (TBR) was calculated for each tumour. Normal subcutaneous tissue had a TBR of 0.3. Necrosis was diagnosed when one or more cold areas were present within the mass. All the animals were sacrificed and histology was available to verify PET results. PET results were concordant with the findings of necropsy and histology in all cases. Results The incidence of the tumour was 69.6% (16/23 animals); seven animals did not develop a malignant mass. Ten of the 23 animals had a positive PET scan 2 days after inoculation. Nine of these ten animals developed a tumour; the remaining animal became negative, at the third scan. The positive predictive value of the early PET scan was 90% (9/10 animals) while the negative predictive value was 46% (6/13 animals). In the whole group of animals, mean TBR increased scan by scan. There was a statistically significant difference in TBR between 2 and 20 days after inoculation. Necrosis was present at the second scan in two animals, at the third scan in six animals and at the fourth scan in 11 animals. Conclusion The high positive predictive value of FDG PET 2 days after inoculation means that an animal with a first positive scan has a very high likelihood of developing a mass and can be treated at an early stage with an experimental drug. Animals negative at this point in time will never develop a mass or will eventually do so at a late phase. As 2 of the 16 (12.5%) positive animals had necrosis at the second scan, indicating a vascular mismatch, it may be argued that animals should be treated 2 days after inoculation to guarantee homogeneous vascularisation (thereby ensuring a good drug supply within the tumour) in all subjects.     

Performance evaluation of the new whole-body PET/CT scanner: Discovery ST

Characterisation of the physical performance of the new integrated PET/CT system Discovery ST (GE Medical Systems) has been performed following the NEMA NU 2-1994 (N-94) and the NEMA NU 2-2001 (N-01) standards in both 2D and 3D acquisition configuration. The Discovery ST combines a four or eight multi-slice helical CT scanner with a PET tomograph which consists of 10,080 BGO crystals arranged in 24 rings. The crystal dimensions are 6.3×6.3×30 mm³ and they are organised in blocks of 6×6 crystals, coupled to a single photomultiplier tube with four anodes. The 24 rings of the PET system allow 47 images to be obtained, spaced by 3.27 mm, and covering an axial field of view of 157 mm. The low- and high-energy thresholds are set to 375 and 650 keV, respectively. The coincidence time window is set to 11.7 ns. Using the NEMA N-94 standard, the main results were: (1) the average (radial and tangential) transverse spatial resolution (FWHM) at 1, 10 and 20 cm off axis was 6.28 mm, 7.09 mm and 7.45 mm in 2D, and 6.68 mm, 7.72 mm and 8.13 mm in 3D; (2) the sensitivity for true events was 8,567 cps/kBq/cc in 2D and 36,649 cps/kBq/cc in 3D; (3) the scatter fraction was 15% in 2D and 30% in 3D; (4) the peak true events rate, the true events rate at 50% of the system dead-time and the true events rate when equal to the random events rate were 750 kcps at 189.81 kBq/cc, 744 kcps at 186.48 kBq/cc and 686 kcps at 150.59 kBq/cc, respectively, in 2D, and 922 kcps at 44.03 kBq/cc, 834 kcps at 53.28 kBq/cc and 921 kcps at 44.03 kBq/cc in 3D; (5) the noise equivalent count (NEC) peak rate was 270 kcps at 34.38 kBq/cc in 3D, with random coincidences estimated by delayed events. Using the NEMA N-01 standards the main results were: (1) the average transverse and axial spatial resolution (FWHM) at 1 cm and 10 cm off axis was 6.28 (4.56) mm and 6.88 (6.11) mm in 2D, and 6.29 (5.68) mm and 6.82 (6.05) mm in 3D; (2) the average sensitivity for the two radial positions (r=0 cm and r=10 cm) was 1.93 cps/kBq in 2D and 9.12 cps/kBq in 3D; (3) the scatter fraction was 19% in 2D and 45% in 3D; (4) the NEC peak rate was 54 kcps at 46.99 kBq/cc in 2D and 45.5 kcps at 10.84 kBq/cc in 3D, when random coincidences were estimated by using k=2 in the NEC formula, while the NEC peak rate was 81 kcps at 64.43 kBq/cc and 66 kcps at 14.86 kBq/cc in 2D and 3D, respectively, when random coincidences were estimated by using k=1 in the NEC formula. The new integrated PET-CT system Discovery ST has good overall performances in both 2D and 3D, with in particular a high sensitivity and a very good 3D NEC response.     

Performance evaluation of microPET: a high-resolution lutetium oxyorthosilicate PET scanner for animal imaging.

A new dedicated PET scanner, microPET, was designed and developed at the University of California, Los Angeles, for imaging small laboratory animals. The goal was to provide a compact system with superior spatial resolution at a fraction of the cost of a clinical PET scanner. METHODS: The system uses fiberoptic readout of individually cut lutetium oxyorthosilicate (LSO) crystals to achieve high spatial resolution. Each microPET detector consists of an 8 x 8 array of 2 x 2 x 10-mm LSO scintillation crystals that are coupled to a 64-channel photomultiplier tube by optical fibers. The tomograph consists of 30 detectors in a continuous ring with a 17.2-cm diameter and fields of view (FOVs) of 11.25 cm in the transaxial direction and 1.8 cm in the axial direction. The system has eight crystal rings and no interplane septa. It operates exclusively in the three-dimensional mode and has an electronically controlled bed that is capable of wobbling with a radius of 300 microm. We describe the performance of the tomograph in terms of its spatial, energy and timing resolution, as well as its sensitivity and counting-rate performance. We also illustrate its overall imaging performance with phantom and animal studies that demonstrate the potential applications of this device to biomedical research. RESULTS: Images reconstructed with three-dimensional filtered backprojection show a spatial resolution of 1.8 mm at the center of the FOV (CFOV), which remains <2.5 mm for the central 5 cm of the transaxial FOV. The resulting volumetric resolution of the system is <8 microL. The absolute system sensitivity measured with a 0.74 MBq (20 microCi) 68Ge point source at the CFOV is 5.62 Hz/kBq. The maximum noise equivalent counting rate obtained with a 6.4-cm diameter cylinder spanning the central 56% of the FOV is 10 kcps, whereas the scatter fraction is 37% at the CFOV for an energy window of 250-650 keV and the same diameter cylinder. CONCLUSION: This is the first PET scanner to use the new scintillator LSO and uses a novel detector design to achieve high volumetric spatial resolution. The combination of imaging characteristics of this prototype system (resolution, sensitivity, counting-rate performance and scatter fraction) opens up new possibilities in the study of animal models with PET.     

Current status and future perspectives of in vivo small animal imaging using radiolabeled nanoparticles

Small animal molecular imaging is a rapidly expanding efficient tool to study biological processes non-invasively. The use of radiolabeled tracers provides non-destructive, imaging information, allowing time related phenomena to be repeatedly studied in a single animal. In the last decade there has been an enormous progress in related technologies and a number of dedicated imaging systems overcome the limitations that the size of small animal possesses. On the other hand, nanoparticles (NPs) gain increased interest, due to their unique properties, which make them perfect candidates for biological applications. Over the past 5 years the two fields seem to cross more and more often; radiolabeled NPs have been assessed in numerous pre-clinical studies that range from oncology, till HIV treatment. In this article the current status in the tools, applications and trends of radiolabeled NPs reviewed.     

Performance evaluation of the microPET R4 PET scanner for rodents

The microPET R4 scanner is a dedicated positron emission tomograph (PET) for studies of rodents. A number of scanner parameters such as spatial resolution, sensitivity, scatter, and count rate performance were determined in this work, which showed that the microPET R4 is a suitable PET scanner for small animals like mice and rats. In the center of the field of view (FOV) a maximal sensitivity of 43.66 cps/kBq for a centered point source was calculated from a measurement with a germanium-68 line source within an energy widow of 250-750 keV. A spatial resolution of 1.85 mm full-width at half-maximum (FWHM) in the axial direction and 1.66 mm FWHM in the transaxial direction was measured in the center with a 1-mm-diameter sodium-22 point source. Within the inner 20 mm of the FOV the volumetric resolution is better than 15.6 micro l, corresponding to a linear resolution of less than 2.5 mm in all three dimensions. Images of a high-resolution phantom and from mice and rat studies illustrate the good performance of the scanner. A maximal noise equivalent count rate (NECR) was reached at 174 kcps for a mouse phantom and at 93 kcps for a rat phantom (energy window 250-750 keV). Scatter fractions were measured between 0.30 and 0.42 for an energy window of 250-750 keV and phantom diameters similar to mice and rats. A comparison with the microPET P4 model for primates illustrates the gain in sensitivity due to a smaller detector ring diameter but also the changes in NECR.     

Performance evaluation of the 32-module quadHIDAC small-animal PET scanner.

The 32-module quadHIDAC is a commercial, high-resolution animal PET scanner, based on gas multiwire proportional chambers. METHODS: Several scanner parameters that characterize the performance of the system were evaluated in this study, such as spatial resolution, absolute sensitivity, scatter, and count rate performance. The spatial resolution has been determined with filtered back-projected images of a point source. A line source, a mouse phantom, and a rat phantom have been used to characterize the count rate performance. The scatter fraction and photon absorption have been measured with a mouse scatter phantom. The absolute sensitivity has been determined using a line source with aluminum shields of different thickness. RESULTS: Spatial resolution (full width at half maximum) offers values of 1.08, 1.08, and 1.04 mm in the radial, tangential, and axial directions, respectively. The maximum count rate is 370 kcps for a line source of 19 MBq activity. Registration of scattered coincidences is caused primarily by photons scattering in the large coincidence detectors. For a mouse-sized object, only 5% of the measured coincidences scatter inside the animal, whereas 32% of the coincidences scatter inside the detectors. Photon attenuation within a mouse phantom was 22%. After scatter corrections, the absolute sensitivity of the system is 15.2 cps/kBq for a point source and 13.7 cps/kBq for a 7.8-cm-long line source. The peak noise equivalent count rates are 67 kcps@209 kBq/mL for the mouse phantom and 52 kcps@96 kBq/mL for the rat phantom. Finally, a comparison has been made with the microPET R4, a commercial scintillation crystal-based PET camera. CONCLUSION: The results confirm that the quadHIDAC PET scanner, with its large cylindric field of view (165-mm diameter, 280-mm axial length), is particularly suitable for imaging small animals such as mice or rats.     

Clinical evaluation of whole-body oncologic PET with time-of-flight and point-spread function for the hybrid PET/MR system

PurposeHybrid positron emission tomography/magnetic resonance (PET/MR) imaging is a new multimodality imaging technology that can provide structural and functional information simultaneously. The aim of this study was to investigate the effects of the time-of-flight (TOF) and point-spread function (PSF) on small lesions observed in PET/MR images from clinical patient image sets.Materials and methodsThis study evaluated 54 small lesions in 14 patients who had undergone ¹⁸F-fluorodeoxyglucose (FDG) PET/MR. Lesions up to 30 mm in diameter were included. The PET data were reconstructed with a baseline ordered-subsets expectation-maximization (OSEM) algorithm, OSEM + PSF, OSEM + TOF and OSEM + TOF + PSF. PET image quality and small lesions were visually evaluated and scored by a 3-point scale. A quantitative analysis was then performed using the mean and maximum standardized uptake value (SUV) of the small lesions (SUV_mean and SUV_max). The lesions were divided into two groups according to the long-axis diameter and the location respectively and evaluated with each reconstruction algorithm. We also evaluated the background signal by analyzing the SUV_liver.ResultsOSEM + TOF + PSF provided the highest value and OSEM + TOF or PSF showed a higher value than OSEM for the visual assessment and quantitative analysis. The combination of TOF and PSF increased the SUV_mean by 26.6% and the SUV_max by 30.0%. The SUV_liverwas not influenced by PSF or TOF. For the OSEM + TOF + PSF model, the change in SUV_mean and SUV_max for lesions <10 mm in diameter was 31.9% and 35.8%, and 24.5% and 27.6% for lesions 10–30 mm in diameter, respectively. The abdominal lesions obtained the higher SUV than those of chest on the images with TOF and/or PSF.ConclusionApplication of TOF and PSF significantly increased the SUV of small lesions in hybrid PET/MR images, potentially improving small lesion detectability.     

食蟹猴动物实验在PET/CT扫描检查中的注意事项

目的 寻找食蟹猴动物实验在PET/CT扫描检查中最佳的扫描参数,获得最佳图像.方法 两只食蟹猴为一雄一雌,对两只食蟹猴分别采用CT多参数扫描和PET的多时段动态断层扫描.结果 扫描条件采用420 mAs、120 kV时,可以获得最佳的图像分辨率和最轻的伪影.PET扫描多时段动态断层扫描的图像中,40～60 min的图像可以获得最佳图像效果.结论 食蟹猴在PET/CT机上行动物实验前,应进行预扫描,选择最佳的扫描参数,才能获得满意的实验结果.     

Determination of tumour hypoxia with the PET tracer [<Superscript>18</Superscript>F]EF3: improvement of the tumour-to-background ratio in a mouse tumour model

Purpose The 2-(2-nitroimidazol-1-yl)-N-(3,3,3-trifluoropropyl)acetamide (EF3) is a 2-nitroimidazole derivative which undergoes bioreductive activation under hypoxic conditions. Using the PET tracer [¹⁸F]EF3 in mice, tumour-to-muscle ratios ranging from 1.3 to 3.5 were observed. This study investigated the impact of various interventions aimed at increasing [¹⁸F]EF3 elimination, thus potentially increasing the tumour-to-noise ratio in mice, by increasing the renal filtration rate (spironolactone, furosemide), decreasing tubular re-absorption (metronidazole, ornidazole, amino acid solution) or stimulating gastro-intestinal elimination (phenobarbital). Methods C3H mice were injected i.v. with an average of 12.95 MBq of [¹⁸F]EF3. Drugs were injected i.v. 15 min before the tracer or daily 4 days prior to the experiment (phenobarbital). Anaesthetised mice were imaged from 30 to 300 min with a dedicated animal PET (Mosaic, Philips). Regions of interest were delineated around the tumour, bladder, heart, liver and leg muscle. Radioactivity was expressed as a percentage of injected activity per gram of tissue. Results Ornidazole decreased the urinary excretion and increased the liver uptake of [¹⁸F]EF3, but without causing any changes in the other organs. Phenobarbital significantly increased the liver concentration and decreased radioactivity in blood and muscle without affecting the tracer uptake in tumour. Consequently, a small but non-significant increase in tumour-to-noise ratio was observed. Although some effects were observed with other drugs, they did not modify the tumour-to-noise ratio. Conclusion Only phenobarbital induced a trend toward an increased tumour-to-noise ratio that could possibly be tested in the clinical situation.     

Design and characterization of an economical 192Ir hemi-brain small animal irradiator

Abstract

Purpose: To describe the design and dosimetric characterization of a simple and economical small animal irradiator.

Materials and methods: A high dose rate (HDR) ¹⁹²Ir brachytherapy source from a commercially available afterloader was used with a 1.3 cm thick tungsten collimator to provide sharp beam penumbra suitable for hemi-brain irradiation of mice. The unit was equipped with continuous gas anesthesia to allow robust animal immobilization. Dosimetric characterization of the device was performed with Gafchromic film measurements.

Results: The tungsten collimator provided a sharp penumbra suitable for hemi-brain irradiation, and dose rates on the order of 200 cGy/minute were achieved. The sharpness of the penumbra attainable with this device compares favorably to those measured experimentally for 6 MV photons, and 6 and 20 MeV electron beams from a linear accelerator, and was comparable to those measured for a 300 kVp orthovoltage beam and a Monte Carlo simulated 90 MeV proton beam.

Conclusions: Due to its simplicity and low cost, the apparatus described is an attractive alternative for small animal irradiation experiments requiring steep dose gradients.     

Improving the quality of small animal brain pinhole SPECT imaging by Bayesian reconstruction

The possibility of using existing hardware makes pinhole single-photon emission computed tomography (SPECT) attractive when pursuing the ultra-high resolution required for small animal brain imaging. Unfortunately, the poor sensitivity and the heavy weight of the collimator hamper the use of pinhole SPECT in animal studies by generating noisy and misaligned projections. To improve the image quality we have developed a new Bayesian reconstruction method, pinhole median root prior (PH-MRP), which prevents the excessive noise accumulation from the projections to the reconstructed image. The PH-MRP algorithm was used to reconstruct data acquired with our small animal rotating device, which was designed to reduce the rotation orbit misalignments. Phantom experiments were performed to test the device and compare the PH-MRP with the conventional Feldkamp-Davis-Kress (FDK) and pinhole ordered subsets maximum likelihood expectation maximisation (PH-OSEM) reconstruction algorithms. The feasibility of the system for small animal brain imaging was studied with Han-Wistar rats injected with ¹²³I-epidepride and ^99mTc-hydroxy methylene diphosphonate. Considering all the experiments, no shape distortions due to orbit misalignments were encountered and remarkable improvements in noise characteristics and also in overall image quality were observed when the PH-MRP was applied instead of the FDK or PH-OSEM. In addition, the proposed methods utilise existing hardware and require only a certain amount of construction and programming work, making them easy to implement.     

Performance of Philips Gemini TF PET/CT scanner with special consideration for its time-of-flight imaging capabilities.

Results from a new PET/CT scanner using lutetium-yttrium oxyorthosilicate (LYSO) crystals for the PET component are presented. This scanner, which operates in a fully 3-dimensional mode, has a diameter of 90 cm and an axial field of view of 18 cm. It uses 4 x 4 x 22 mm(3) LYSO crystals arranged in a pixelated Anger-logic detector design. This scanner was designed to perform as a high-performance conventional PET scanner as well as provide good timing resolution to operate as a time-of-flight (TOF) PET scanner. METHODS: Performance measurements on the scanner were made using the National Electrical Manufacturers Association (NEMA) NU2-2001 procedures to benchmark its conventional imaging capabilities. The scatter fraction and noise equivalent count (NEC) measurements with the NEMA cylinder (20-cm diameter) were repeated for 2 larger cylinders (27-cm and 35-cm diameter), which better represent average and heavy patients. New measurements were designed to characterize its intrinsic timing resolution capability, which defines its TOF performance. Additional measurements to study the impact of pulse pileup at high counting rates on timing, as well as energy and spatial, resolution were also performed. Finally, to characterize the effect of TOF reconstruction on lesion contrast and noise, the standard NEMA/International Electrotechnical Commission torso phantom as well as a large 35-cm-diameter phantom with both hot and cold spheres were imaged for varying scan times. RESULTS: The transverse and axial resolution near the center is 4.8 mm. The absolute sensitivity of this scanner measured with a 70-cm-long line source is 6.6 cps/kBq, whereas scatter fraction is 27% measured with a 70-cm-long line source in a 20-cm-diameter cylinder. For the same line source cylinder, the peak NEC rate is measured to be 125 kcps at an activity concentration of 17.4 kBq/mL (0.47 microCi/mL). The 2 larger cylinders showed a decrease in the peak NEC due to increased attenuation, scatter, and random coincidences, and the peak occurs at lower activity concentrations. The system coincidence timing resolution was measured to be 585 ps. The timing resolution changes as a function of the singles rate due to pulse pileup and could impact TOF image reconstruction. Image-quality measurements with the torso phantom show that very high quality images can be obtained with short scan times (1-2 min per bed position). However, the benefit of TOF is more apparent with the large 35-cm-diameter phantom, where small spheres are detectable only with TOF information for short scan times. CONCLUSION: The Gemini TF whole-body scanner represents the first commercially available fully 3-dimensional PET scanner that achieves TOF capability as well as conventional imaging capabilities. The timing resolution is also stable over a long duration, indicating the practicality of this device. Excellent image quality is achieved for whole-body studies in 10-30 min, depending on patient size. The most significant improvement with TOF is seen for the heaviest patients.     

Performance evaluation of the GE healthcare eXplore VISTA dual-ring small-animal PET scanner.

We evaluated the performance characteristics of the eXplore VISTA dual-ring small-animal PET scanner, a stationary, ring-type, depth-of-interaction (DOI) correcting system designed to simultaneously maximize sensitivity, resolution, and resolution uniformity over a field of view sufficient to image rodent-sized animals. METHODS: We measured the intrinsic spatial resolution response of the VISTA detector modules, spatial and volume resolution throughout a representative portion of the field of view, and imaged several common resolution phantoms to provide a qualitative picture of resolution performance. We obtained an axial sensitivity profile and measured central point source sensitivity, scatter fractions and noise equivalent count (NEC) rates for rat- and mouse-sized objects using different energy windows, and count rate linearity. In addition, we measured the energy and timing resolution of both of the crystal layers (cerium-doped gadolinium orthosilicate and cerium-doped lutetium-yttrium orthosilicate) that give VISTA machines a DOI compensation capability. We examined the effectiveness of this DOI compensation by comparing spatial resolution measurements with and without the DOI correction enabled. Finally, several animal studies were included to illustrate system performance in the field. RESULTS: Spatial and volume resolutions averaged approximately 1.4 mm and 2.9 mm(3), respectively (with 3-dimensional Fourier rebinning and 2-dimensional filtered backprojection image reconstructions and an energy window of 250-700 keV), along the central axis of the scanner, and the spatial resolution was better than 1.7 mm and 2.1 mm at 1 and 2 cm off the central axis, respectively. Central point source sensitivity measured approximately 4% with peak NEC rates of 126.8 kcps at 455 kBq/mL and 77.1 kcps at 141 kBq/mL for mouse- and rat-sized uniform, cylindric phantoms, respectively. The radial spatial resolution at 2.8 cm off axis with DOI compensation was 2.5 mm but degraded (by 56%) to 3.9 mm without DOI compensation (as would be the case with a geometrically identical scanner without DOI correction capability). CONCLUSION: These results indicate that the VISTA small-animal PET scanner is well suited to imaging rodent-sized animals. The combination of high spatial resolution, resolution uniformity, sensitivity, and count rate performance, made possible in part by the novel use of phoswich detector modules, confers significant technical advantages over machines with similar geometry but without DOI correction capability.     

Clinical evaluation of 2D versus 3D whole-body PET image quality using a dedicated BGO PET scanner

Purpose Three-dimensional positron emission tomography (3D PET) results in higher system sensitivity, with an associated increase in the detection of scatter and random coincidences. The objective of this work was to compare, from a clinical perspective, 3D and two-dimensional (2D) acquisitions in terms of whole-body (WB) PET image quality with a dedicated BGO PET system.Methods 2D and 3D WB emission acquisitions were carried out in 70 patients. Variable acquisition parameters in terms of time of emission acquisition per axial field of view (aFOV) and slice overlap between sequential aFOVs were used during the 3D acquisitions. 3D and 2D images were reconstructed using FORE+WLS and OSEM respectively. Scatter correction was performed by convolution subtraction and a model-based scatter correction in 2D and 3D respectively. All WB images were attenuation corrected using segmented transmission scans. Images were blindly assessed by three observers for the presence of artefacts, confidence in lesion detection and overall image quality using a scoring system.Results Statistically significant differences between 2D and 3D image quality were only obtained for 3D emission acquisitions of 3 min. No statistically significant differences were observed for image artefacts or lesion detectability scores. Image quality correlated significantly with patient weight for both modes of operation. Finally, no differences were seen in image artefact scores for the different axial slice overlaps considered, suggesting the use of five slice overlaps in 3D WB acquisitions.Conclusion 3D WB imaging using a dedicated BGO-based PET scanner offers similar image quality to that obtained in 2D considering similar overall times of acquisitions.