Yuan-Chuan Tai

Performance evaluation of the microPET P4: a PET system dedicated to animal imaging

The microPET Primate 4-ring system (P4) is an animal PET tomograph with a 7.8 cm axial extent, a 19 cm diameter transaxial field of view (FOV) and a 22 cm animal port. The system is composed of 168 detector modules, each with an 8 x 8 array of 2.2 x 2.2 x 10 mm3 lutetium oxyorthosilicate crystals, arranged as 32 crystal rings 26 cm in diameter. The detector crystals are coupled to a Hamamatsu R5900-C8 PS-PMT via a 10 cm long optical fibre bundle. The detectors have a timing resolution of 3.2 ns, an average energy resolution of 26%, and an average intrinsic spatial resolution of 1.75 mm. The system operates in 3D mode without inter-plane septa, acquiring data in list mode. The reconstructed image spatial resolution ranges from 1.8 mm at the centre to 3 mm at 4 cm radial offset. The tomograph has a peak system sensitivity of 2.25% at the centre of the FOV with a 250-750 keV energy window. The noise equivalent count rate peaks at 100-290 kcps for representative object sizes. Images from two phantoms and three different types of laboratory animal demonstrate the advantage of the P4 system over the original prototype microPET. including its threefold improvement in sensitivity and a large axial FOV sufficient to image an entire mouse in a single bed position.

MicroPET II: design, development and initial performance of an improved microPET scanner for small-animal imaging

MicroPET II is a second-generation animal PET scanner designed for high-resolution imaging of small laboratory rodents. The system consists of 90 scintillation detector modules arranged in three contiguous axial rings with a ring diameter of 16.0 cm and an axial length of 4.9 cm. Each detector module consists of a 14 x 14 array of lutetium oxyorthosilicate (LSO) crystals coupled to a multi-channel photomultiplier tube (MC-PMT) through a coherent optical fibre bundle. Each LSO crystal element measures 0.975 mm x 0.975 mm in cross section by 12.5 mm in length. A barium sulphate reflector material was used between LSO elements leading to a detector pitch of 1.15 mm in both axial and transverse directions. Fused optical fibre bundles were made from 90 microm diameter glass fibres with a numerical aperture of 0.56. Interstitial extramural absorber was added between the fibres to reduce optical cross talk. A charge-division readout circuit was implemented on printed circuit boards to decode the 196 crystals in each array from the outputs of the 64 anode signals of the MC-PMT. Electronics from Concorde Microsystems Inc. (Knoxville, TN) were used for signal amplification, digitization, event qualification, coincidence processing and data capture. Coincidence data were passed to a host PC that recorded events in list mode. Following acquisition, data were sorted into sinograms and reconstructed using Fourier rebinning and filtered hackprojection algorithms. Basic evaluation of the system has been completed. The absolute sensitivity of the microPET II scanner was 2.26% at the centre of the field of view (CFOV) for an energy window of 250-750 keV and a timing window of 10 ns. The intrinsic spatial resolution of the detectors in the system averaged 1.21 mm full width at half maximum (FWHM) when measured with a 22Na point source 0.5 mm in diameter. Reconstructed image resolution ranged from 0.83 mm FWHM at the CFOV to 1.47 mm FWHM in the radial direction, 1.17 mm FWHM in the tangential direction and 1.42 mm FWHM in the axial direction at 1 cm offset from the CFOV. These values represent highly significant improvements over our earlier microPET scanner (approximately fourfold sensitivity increase and 25-35% improvement in linear spatial resolution under equivalent operating conditions) and are expected to be further improved when the system is fully optimized.

Optimization and performance evaluation of the microPET II scanner for in vivo small-animal imaging

MicroPET II is a newly developed PET (positron emission tomography) scanner designed for high-resolution imaging of small animals. It consists of 17,640 LSO crystals each measuring 0.975 x 0.975 x 12.5 mm3, which are arranged in 42 contiguous rings, with 420 crystals per ring. The scanner has an axial field of view (FOV) of 4.9 cm and a transaxial FOV of 8.5 cm. The purpose of this study was to carefully evaluate the performance of the system and to optimize settings for in vivo mouse and rat imaging studies. The volumetric image resolution was found to depend strongly on the reconstruction algorithm employed and averaged 1.1 mm (1.4 microl) across the central 3 cm of the transaxial FOV when using a statistical reconstruction algorithm with accurate system modelling. The sensitivity, scatter fraction and noise-equivalent count (NEC) rate for mouse- and rat-sized phantoms were measured for different energy and timing windows. Mouse imaging was optimized with a wide open energy window (150-750 keV) and a 10 ns timing window, leading to a sensitivity of 3.3% at the centre of the FOV and a peak NEC rate of 235,000 cps for a total activity of 80 MBq (2.2 mCi) in the phantom. Rat imaging, due to the higher scatter fraction, and the activity that lies outside of the field of view, achieved a maximum NEC rate of 24,600 cps for a total activity of 80 MBq (2.2 mCi) in the phantom, with an energy window of 250-750 keV and a 6 ns timing window. The sensitivity at the centre of the FOV for these settings is 2.1%. This work demonstrates that different scanner settings are necessary to optimize the NEC count rate for different-sized animals and different injected doses. Finally, phantom and in vivo animal studies are presented to demonstrate the capabilities of microPET II for small-animal imaging studies.

Detector development for microPET II: A 1 μl resolution PET scanner for small animal imaging

We are currently developing a small animal positron emission tomography (PET) scanner with a design goal of 1 microlitre (1 mm3) image resolution. The detectors consist of a 12 x 12 array of 1 x 1 x 10 mm lutetium oxyorthosilicate (LSO) scintillator crystals coupled to a 64-channel photomultiplier tube (PMT) via 5 cm long optical fibre bundles. The optical fibre connection allows a high detector packing fraction despite the dead space surrounding the active region of the PMT. Optical fibre bundles made from different types of glass were tested for light transmission, and also their effects on crystal identification and energy resolution, and compared to direct coupling of the LSO arrays to the PMTs. We also investigated the effects of extramural absorber (EMA) in the fibre bundles. Based on these results, fibre bundles manufactured from F2 glass were selected. We built three pairs of prototype detectors (directly coupled LSO array, fibre bundle without EMA and fibre bundle with EMA) and measured flood histograms, energy resolution, intrinsic spatial resolution and timing resolution. The results demonstrated an intrinsic spatial resolution (FWHM) of 1.12 mm (directly coupled), 1.23 mm (fibre bundle without EMA coupling) and 1.27 mm (fibre bundle with EMA coupling) using an approximately 500 microm diameter Na-22 point source. Using a 330 microm outer diameter steel needle line source filled with F-18, spatial resolution for the detector with the EMA optical fibre bundle improved to 1.05 mm. The respective timing and energy FWHM values were 1.96 ns, 21% (directly coupled), 2.20 ns, 23% (fibre bundle without EMA) and 2.99 ns, 30% (fibre bundle with EMA). The peak-to-valley ratio in the flood histograms was better with EMA (5:1) compared to the optical fibre bundle without EMA (2.5:1), due to the decreased optical cross-talk. In comparison to the detectors used in our current generation microPET scanner, these detectors substantially improve on the spatial resolution, preserve the timing resolution and provide adequate energy resolution for a modern high-resolution animal PET tomograph.

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.

Virtual-Pinhole PET

We proposed and tested a novel geometry for PET system design analogous to pinhole SPECT called the virtual-pinhole PET (VP-PET) geometry to determine whether it could provide high-resolution images. Methods: We analyzed the effects of photon acolinearity and detector sizes on system resolution and extended the empiric formula for reconstructed image resolution of conventional PET proposed earlier to predict the resolutions of VP-PET. To measure the system resolution of VP-PET, we recorded coincidence events as a 22Na point source was stepped across the coincidence line of response between 2 detectors made from identical arrays of 12 × 12 lutetium oxyorthosilicate crystals (each measuring 1.51 × 1.51 × 10 mm3) separated by 565 mm. To measure reconstructed image resolution, we built 4 VP-PET systems using 4 types of detectors (width, 1.51–6.4 mm) and imaged 4 point sources of 64Cu (half-life = 12.7 h to allow a long acquisition time). Tangential and radial resolutions were measured and averaged for each source and each system. We then imaged a polystyrene plastic phantom representing a 2.5-cm-thick cross-section of isolated breast volume. The phantom was filled with an aqueous solution of 64Cu (713 kBq/mL) in which the following were imbedded: 4 spheric tumors ranging from 1.8 to 12.6 mm in inner diameter (ID), 6 micropipettes (0.7- or 1.1-mm ID filled with 64Cu at 5×, 20×, or 50× background), and a 10.0-mm outer-diameter cold lesion. Results: The shape and measured full width at half maximum of the line spread functions agree well with the predicted values. Measured reconstructed image resolution (2.40–3.24 mm) was ±6% of the predicted value for 3 of the 4 systems. In one case, the difference was 12.6%, possibly due to underestimation of the block effect from the low-resolution detector. In phantom experiments, all spheric tumors were detected. Small line sources were detected if the activity concentration is at least 20× background. Conclusion: We have developed and characterized a novel geometry for PET. A PET system following the VP-PET geometry provides high-resolution images for objects near the systems high-resolution detectors. This geometry may lead to the development of special-purpose PET systems or resolution-enhancing insert devices for conventional PET scanners.

Noninvasive Measurement of Myocardial Activity Concentrations and Perfusion Defect Sizes in Rats With a New Small-Animal Positron Emission Tomograph

Background—We explored the feasibility of measuring regional tracer activity concentrations and flow defects in myocardium of rats with a high spatial resolution small-animal PET system (microPET). Methods and Results—Myocardial images were obtained after intravenous 18F-fluorodeoxyglucose (18FDG) in 11 normal rats (group 1) and assembled into polar maps. Regional 18F activity concentrations were measured in 9 regions of interest and compared with tissue activity concentrations measured by well counting. In another 9 rats (group 2), myocardial perfusion images were acquired with 13N-ammonia at baseline and during coronary occlusion. On the polar maps recorded during coronary occlusion, the size of perfusion defects was measured as the myocardium with <50% of maximum activity and expressed as percent total myocardium and was correlated with the area at risk defined by postmortem staining. The diagnostic quality of 18FDG and 13N-ammonia microPET images was good to excellent; the images were easily assembled into polar maps. In group 1, regional 18F concentrations by microPET and postmortem were correlated linearly (r =0.99;P <0.01 for average and r =0.97;P <0.01 for regional concentrations). In group 2, perfusion defect sizes by microPET and postmortem were correlated linearly (P <0.01;r =0.93). Conclusions—The findings indicate the feasibility of noninvasive studies of the myocardium in rats with a dedicated small-animal PET-imaging device.

A sub-millimeter resolution PET detector module using a multi-pixel photon counter array

The aim of this study is to design a novel PET detector module using an array of sub-millimeter LSO crystal read out by an array of surface-mount type of Multi-Pixel Photon Counter (MPPC). The volume of one MPPC sensor is 2.4 × 1.9 × 0.8 mm3 and the sensitive area is 1 × 1 mm2. The 9 MPPCs were arranged into a 3 by 3 array held by a Teflon base with 9 pockets. This provides an 8.6 × 8.6 mm2 sensing area to decode a 10 by 10 array with 0.8 × 0.8 × 3 mm3 LSO crystals of 0.86 mm pitch. After all the components were assembled, the base was mounted to a readout board that consists of quenching resistors, coupling capacitors, resistive charge divider, and current feedback pre-amplifiers. A light guide was fabricated to control the distribution of scintillation lights generated from the LSO array on the MPPC sensitive area so as to get a better localization of each gamma-ray event. A Monte Carlo simulation program was utilized to assist the light guide design. For the flood image measurement, a Na-22 point source was used. The energy resolution was measured with a Ge-68 source for each LSO crystal by a Gaussian fit to the photopeak in its energy spectrum. Timing resolution was measured against a plastic scintillator coupled to a Hamamatsu H5783 PMT using a standard time-to-amplitude converter. Linearity test was performed with gamma-ray sources of various energies. The 10 by 10 array of 0.8 mm LSO crystals can be clearly resolved in the flood image. Timing resolution of the single channel MPPC was estimated to be 620 picoseconds FWHM. Mean energy resolution and standard deviation value were 18.8% FWHM and ± 2.7% at 511 keV. The nonlinearity is observed at the single MPPC and the corner crystals in the MPPC array, but less significant for central crystal. These results demonstrate that the proposed PET detector module can be used for high resolution PET insert applications. It can potentially be used for MR compatible PET applications.

Utilization of 3-D elastic transformation in the registration of chest X-ray CT and whole body PET

Describes a 3-D elastic transformation which compensates for the non-rigid deformation of the chest that is seen in X-ray CT relative to PET images of the thorax. X-ray CT is widely used for detection and localization of lesions in the thorax. Whole Body PET with 18-FDG is accepted for staging and for measuring tumor response to therapy. The combination of these two modalities to locate metabolically active tumors in CT images should prove to be of significant value in lung cancer staging and treatment planning. Due to the differences in the acquisition conventions and scan duration, the subjects arms are positioned overhead for X-ray CT or at the side for PET, causing a change in the shape of the thorax, requiring non-rigid transformations to achieve proper registration. Techniques to register chest X-ray CT and Whole Body PET images were developed and evaluated. The accuracy of 3-D elastic transformation was tested by phantom study. Studies on patients with lung carcinoma were used to assess the technique for localizing 18-FDG uptake and for correlating PET transmission to X-ray CT images. Results showed that the elastic transformation provided an accurate alignment and reliable correlation of the detailed anatomy of the CT with the functional information of the PET images.

Positron range modeling for statistical PET image reconstruction

Positron range is one of the factors that fundamentally limits the spatial resolution of PET images. With the higher resolution of small animal imaging systems and increased interest in using higher energy positron emitters, it is important to consider range effects when designing image reconstruction methods. The positron range distribution can be measured experimentally or calculated using approximate analytic formulae or Monte Carlo simulations. We investigate the use of this distribution within a MAP image reconstruction framework. Positron range is modeled as a blurring kernel and included as part of the forward projection matrix. We describe the use of a 3D isotropic shift-invariant blur kernel, which assumes that positrons are propagating in a homogeneous medium and is computed by Monte Carlo simulation using EGS4. We also propose a new shift-variant blurring model for positron range that accounts for spatial inhomogeneities in the positron scatter properties of the medium. Monte Carlo simulations, phantom, and animal studies with the isotopes Cu-60 and Cu-64 are presented.