Qinan Bao

Performance Evaluation of the Inveon Dedicated PET Preclinical Tomograph Based on the NEMA NU-4 Standards

The Inveon dedicated PET (DPET) scanner is the latest generation of preclinical PET systems devoted to high-resolution and high-sensitivity murine model imaging. In this study, we report on its performance based on the National Electrical Manufacturers Association (NEMA) NU-4 standards. Methods: The Inveon DPET consists of 64 lutetium oxyorthosilicate block detectors arranged in 4 contiguous rings, with a 16.1-cm ring diameter and a 12.7-cm axial length. Each detector block consists of a 20 × 20 lutetium oxyorthosilicate crystal array of 1.51 × 1.51 × 10.0 mm elements. The scintillation light is transmitted to position-sensitive photomultiplier tubes via optical light guides. Energy resolution, spatial resolution, sensitivity, scatter fraction, and counting-rate performance were evaluated. The NEMA NU-4 image–quality phantom and a healthy mouse injected with 18F-FDG and 18F− were scanned to evaluate the imaging capability of the Inveon DPET. Results: The energy resolution at 511 keV was 14.6% on average for the entire system. In-plane radial and tangential resolutions reconstructed with Fourier rebinning and filtered backprojection algorithms were below 1.8-mm full width at half maximum (FWHM) at the center of the field of view. The radial and tangential resolution remained under 2.0 mm, and the axial resolution remained under 2.5-mm FWHM within the central 4-cm diameter of the field of view. The absolute sensitivity of the system was 9.3% for an energy window of 250–625 keV and a timing window of 3.432 ns. At a 350- to 625-keV energy window and a 3.432-ns timing window, the peak noise equivalent counting rate was 1,670 kcps at 130 MBq for the mouse-sized phantom and 590 kcps at 110 MBq for the rat-sized phantom. The scatter fractions at the same acquisition settings were 7.8% and 17.2% for the mouse- and rat-sized phantoms, respectively. The mouse image-quality phantom results demonstrate that for typical mouse acquisitions, the image quality correlates well with the measured performance parameters in terms of image uniformity, recovery coefficients, attenuation, and scatter corrections. Conclusion: The Inveon system, compared with previous generations of preclinical PET systems from the same manufacturer, shows significantly improved energy resolution, sensitivity, axial coverage, and counting-rate capabilities. The performance of the Inveon is suitable for successful murine model imaging experiments.

NEMA NU 4-2008 Comparison of Preclinical PET Imaging Systems

The National Electrical Manufacturers Association (NEMA) standard NU 4-2008 for performance measurements of small-animal tomographs was recently published. Before this standard, there were no standard testing procedures for preclinical PET systems, and manufacturers could not provide clear specifications similar to those available for clinical systems under NEMA NU 2-1994 and 2-2001. Consequently, performance evaluation papers used methods that were modified ad hoc from the clinical PET NEMA standard, thus making comparisons between systems difficult. Methods: We acquired NEMA NU 4-2008 performance data for a collection of commercial animal PET systems manufactured since 2000: microPET P4, microPET R4, microPET Focus 120, microPET Focus 220, Inveon, ClearPET, Mosaic HP, Argus (formerly eXplore Vista), VrPET, LabPET 8, and LabPET 12. The data included spatial resolution, counting-rate performance, scatter fraction, sensitivity, and image quality and were acquired using settings for routine PET. Results: The data showed a steady improvement in system performance for newer systems as compared with first-generation systems, with notable improvements in spatial resolution and sensitivity. Conclusion: Variation in system design makes direct comparisons between systems from different vendors difficult. When considering the results from NEMA testing, one must also consider the suitability of the PET system for the specific imaging task at hand.

Estimation of the minimum detectable activity of preclinical PET imaging systems with an analytical method.

PURPOSE The traditional figures of merit used in the evaluation of positron emission tomography (PET) systems, including system sensitivity and spatial resolution, do not directly reflect the minimum detectable activity (MDA) performance, despite the fact that it is one of the most important tasks for a PET system. MDA, as a combination of the more traditional PET system parameters, is directly related to lesion detection. However, MDA evaluation is task specific and cannot be done by a single measurement. Therefore, a simple method to evaluate system detectability needs to be developed. METHODS In this work, an analytical method of MDA estimation was developed, taking into account system sensitivity, spatial resolution, source properties, and noise propagation in image reconstruction by using the Rose criterion and/or the Curie equation as the detection standard. In the implementation, the source background, as well as the intrinsic activity background from the scintillation material of the system, was also taken into consideration. The accuracy of this method was evaluated in two commercially available preclinical PET systems, with phantom experiments that were designed to closely mimic in vivo tumor uptake without introducing finite boundaries between the source and the background. RESULTS The lesion contrast-to-noise ratio calculated by the analytical evaluation showed good agreement with that obtained from the experiments. Visual assessment of the reconstructed images at the detection limit (based on analytical evaluation) also was in agreement with the Rose criterion. The MDA performance was quantitatively compared between the two preclinical PET systems and showed different detection limits under different imaging conditions, suggesting that the detection limit of a PET system strongly depends on the lesion properties and acquisition settings. CONCLUSIONS An analytical method of evaluating the PET system detectability was developed and validated by experiments. Overall, the analytical MDA calculation provides a simple way to evaluate the signal detectability of a PET system and can be used for comparing different systems. It also provides guidelines for designing new PET tomographs as well as optimizing data acquisition protocols.

In Vivo Mouse Bioluminescence Tomography with Radionuclide-Based Imaging Validation

IntroductionBioluminescence imaging, especially planar bioluminescence imaging, has been extensively applied in in vivo preclinical biological research. Bioluminescence tomography (BLT) has the potential to provide more accurate imaging information due to its 3D reconstruction compared with its planar counterpart.MethodsIn this work, we introduce a positron emission tomography (PET) radionuclide imaging-based strategy to validate the BLT results. X-ray computed tomography, PET, spectrally resolved bioluminescence imaging, and surgical excision were performed on a tumor xenograft mouse model expressing a bioluminescent reporter gene.ResultsWith different spectrally resolved measured data, the BLT reconstructions were acquired based on the third-order simplified spherical harmonics (SP3) approximation and the diffusion approximation (DA). The corresponding tomographic images were obtained for validation of bioluminescence source reconstruction.ConclusionOur results show the strength of PET imaging compared with other validation methods for BLT and improved source localization accuracy based on the SP3 approximation compared with the diffusion approximation.

Performance Characteristics of BGO Detectors for a Low Cost Preclinical PET Scanner

PETbox is a low-cost benchtop PET scanner dedicated to high throughput preclinical imaging that is currently under development at our institute. This paper presents the design and characterization of the detectors that are used in the PETbox system. In this work, bismuth germanate scintillator was used for the detector, taking advantage of its high stopping power, high photoelectric event fraction, lack of intrinsic background radiation and low cost. The detector block was segmented into a pixelated array consisting of 20 × 44 elements, with a crystal pitch of 2.2 mm and a crystal cross section of 2 mm × 2 mm. The effective area of the array was 44 mm × 96.8 mm. The array was coupled to two Hamamatsu H8500 position sensitive photomultiplier tubes, forming a flat-panel type detector head with a sensitive area large enough to cover the whole body of a typical laboratory mouse. Two such detector heads were constructed and their performance was characterized. For one detector head, the energy resolution ranged from 16.1% to 38.5% full width at half maximum (FWHM), with a mean of 20.1%; for the other detector head, the energy resolution ranged from 15.5% to 42.7% FWHM, with a mean of 19.6 %. The intrinsic spatial resolution was measured to range from 1.55 mm to 2.39 mm FWHM along the detector short axis and from 1.48 mm to 2.33 mm FWHM along the detector long axis, with an average of 1.78 mm. Coincidence timing resolution for the detector pair was measured to be 4.1 ns FWHM. These measurement results show that the detectors are suitable for our specific application.

Performance evaluation of PETbox: A low cost bench top PET scanner dedicated to high throughput preclinical imaging

PETbox is designed to be a low cost and easy to use bench top small animal PET scanner dedicated for high throughput quantitative pharmacokinetic and pharmacodynamic studies. To achieve this goal, the scanner is integrated with a complete animal management system that provides life support including reproducible positioning, temperature control, anesthesia, real-time monitoring of animal respiration and a pathogen barrier. This approach minimizes the overall cost and complexity of preclinical PET imaging and should enable non-imaging scientists to embrace the technology. The system uses two opposing detector heads, each one consisting of a pixilated BGO array coupled to two H8500 multi-channel photomultiplier tubes. The BGO crystals were segmented into 20 ? 44 arrays with a pixel pitch of 2.2 mm and a total active area of 44 mm ? 96.8 mm. Position and timing signals from the photomultiplier tube readout circuitry were connected to a field programmable gate array (FPGA) board with eight ADC channels, each running at 100 MHz. Signal processing algorithms were developed for the FPGA to process received PET events and raw list-mode data were generated by the FPGA board and transferred to a host PC for storage. Basic system performance parameters were measured. The system has an average intrinsic spatial resolution of 1.72 mm FWHM along detector long axis and 1.84 mm FWHM along detector short axis. The coincidence timing resolution was measured to be 4.1 ns FWHM. The average energy resolution of the crystals was 19.8% and the absolute sensitivity of the system was measured to be 3.8% at the center of the gantry. Initial imaging studies were also performed with live mice. A mouse tumor xenograft was imaged 1 hour after a 32uCi [18F]FDG injection for 20 minutes. 3D images were generated using a ML-EM method. Results demonstrate the capability and potential of the PETbox system for dedicated high throughput mouse studies such as biodistribution and organ uptake quantification.

GATE Simulation of a BGO Based High Sensitivity Small Animal PET Scanner

A BGO based small animal PET scanner dedicated for imaging small rodent was simulated by GATE. The virtual PET scanner had the same ring diameter, axial field of view (FOV) and crystal arrangement as the LSO based Siemens Inveon PET system, but was simulated with varied crystal lengths. The simulated system sensitivity was 11.6%, 19.3% and 25.5% for 10, 15 and 20 mm BGO at an energy window of 250-750 keV. The spatial resolution was measured at radial offsets of 0, 15 and 28 mm from the center of the FOV for the three crystal thicknesses. The FWHM in the radial and tangential directions was below 2.5 mm and 1.8 mm respectively for all three crystal thicknesses, up to a 30 mm diameter FOV. Scatter fraction and count rate performance were measured using a line source inserted in a water cylinder 70 mm long and 25 mm diameter for the 20 mm BGO system. The maximum NECR was 0.99 Mcps at 24 MBq and the phantom scatter fraction was 4.5% with an energy window of 250-750 keV and a timing window of 12 ns. The BGO based PET scanner was compared with the Inveon and the microPET Focus 220 systems. With the same crystal thickness, the BGO scanner had higher system sensitivity than the LSO and further improvement in sensitivity can be achieved by using thicker crystals without sacrificing much spatial resolution. Both radial and tangential resolutions were comparable to the LSO based systems. At the evaluated energy window of 250-750 keV, the phantom scatter fraction was similar to the Inveon system, while the crystal scatter fraction was about 10% lower. The maximum NECR was lower than Inveon and was achieved at a lower activity level. Simulation of the BGO PET scanner proved the design concept of a high sensitivity small animal PET scanner, with comparable spatial resolution, similar phantom scatter fraction, and acceptable count rate performance.

Monte Carlo based estimation of detector response in a large solid angle Preclinical PET imaging system

Small animal PET imaging imposes high performance requirements on image resolution and system sensitivity. Scanners with larger solid angle, achieved by using smaller crystal ring diameter and longer axial field-of-view (FOV), have higher absolute sensitivity. The Inveon dedicated PET (DPET) system, the latest generation of commercial tomographs from Siemens Preclinical Solutions, Inc., is such a high sensitivity scanner. Its crystal ring diameter and axial extent is 16.1 cm and 12.7 cm respectively, which give a solid angle coverage of 62%. However, this geometry also accentuates inter-crystal penetration, especially in the axial direction and causes axial blurring. Axial and radial blurring recovery is crucial for high resolution small animal PET imaging. System response modeling in combination with iterative reconstruction algorithms like Maximum a posteriori reconstruction (MAP) can be used to recover the resolution loss. Blurring in both radial and axial directions were simulated in GATE with a planar strip of 18F source placed inside the Inveon scanner. Detector response for each possible line of response (LOR) was calculated and can be incorporated into iterative reconstruction algorithms. As the entrance ring difference (δ) increased, the recorded coincidences tended to shift to a larger ring difference. As the entrance radial offset (u) increased, the recorded coincidences tended to shift to a smaller radial offset. The blurring effect got larger as δ and/or u increased. A real 18F plane source printed on carbon paper was also imaged and compared with the simulation data as a validation. The coincidence counts recorded for each ring difference showed a very good agreement between simulation and experiment except for very large oblique angles. This discrepancy should be improved with the inclusion of the scanner end shields in future simulations.

Image reconstruction for PETbox, a benchtop preclinical PET tomograph

PETbox, an integrated low-cost benchtop preclinical PET scanner dedicated to high throughput quantitative mouse studies is currently under development at the Crump Institute for Molecular Imaging, UCLA. The system employs two opposing flat panel BGO detector blocks on a static gantry and produces a limited number of projection angles around a central antero-posterior (AP) view. Iterative reconstruction based on a Maximum Likelihood and Expectation Maximization (ML-EM) algorithm was developed with incorporation of a probability matrix, which takes into account the detection probability and inter-crystal scattering. Point sources at different positions were simulated with the GATE software package and showed a peak sensitivity of 3.87% at a 150-650 keV energy window. When applying a sensitivity correction map, the image values of the reconstructed point sources at different positions are within a 5.3% standard deviation, indicating good quantification accuracy. The spatial resolution of point sources is largely uniform along the coronal direction across the field of view (FOV) with worse resolution along the direction orthogonal to the detector blocks, which is mainly due to the reduced spatial sampling in that direction. A voxelized digital mouse (Moby phantom) was also simulated and then iteratively reconstructed. Attenuation and non-uniform sensitivity corrections were applied. Quantification accuracy was evaluated with the reconstructed Moby data and two analytically simulated data sets. To a first approximation, reasonably good quantification accuracy was obtained for most important organs with the PETbox reconstructed image. This evaluation indicates that the integrated detector system design, reconstruction algorithm and attenuation correction work well, which is very important for quantitative pharmacokinetic and pharmacodynamic studies. In-vivo mouse studies were also acquired and reconstructed. The obtained images proved the capability of PETbox as a dedicated mouse scanner for both dynamic and static acquisitions.

Optimization of the Energy Window for PETbox4, a Preclinical PET Tomograph With a Small Inner Diameter

Small animal positron emission tomography (PET) systems are often designed by employing close geometry configurations. Due to the different characteristics caused by geometrical factors, these tomographs require data acquisition protocols that differ from those optimized for conventional large diameter ring systems. In this work we optimized the energy window for data acquisitions with PETbox4, a 50 mm detector separation (box-like geometry) pre-clinical PET scanner, using the Geant4 Application for Tomographic Emission (GATE). The fractions of different types of events were estimated using a voxelized phantom including a mouse as well as its supporting chamber, mimicking a realistic mouse imaging environment. Separate code was developed to extract additional information about the gamma interactions for more accurate event type classification. Three types of detector backscatter events were identified in addition to the trues, phantom scatters and randoms. The energy window was optimized based on the noise equivalent count rate (NECR) and scatter fraction (SF) with lower-level discriminators (LLD) corresponding to energies from 150 keV to 450 keV. The results were validated based on the calculated image uniformity, spillover ratio (SOR) and recovery coefficient (RC) from physical measurements using the National Electrical Manufacturers Association (NEMA) NU-4 image quality phantom. These results indicate that when PETbox4 is operated with a more narrow energy window (350-650 keV), detector backscatter rejection is unnecessary. For the NEMA NU-4 image quality phantom, the SOR for the water chamber decreases by about 45% from 15.1% to 8.3%, and the SOR for the air chamber decreases by 31% from 12.0% to 8.3% at the LLDs of 150 and 350 keV, without obvious change in uniformity, further supporting the simulation based optimization. The optimization described in this work is not limited to PETbox4, but also applicable or helpful to other small inner diameter geometry scanners.