Arion F. Chatziioannou

GATE: a simulation toolkit for PET and SPECT.

Monte Carlo simulation is an essential tool in emission tomography that can assist in the design of new medical imaging devices, the optimization of acquisition protocols and the development or assessment of image reconstruction algorithms and correction techniques. GATE, the Geant4 Application for Tomographic Emission, encapsulates the Geant4 libraries to achieve a modular, versatile, scripted simulation toolkit adapted to the field of nuclear medicine. In particular, GATE allows the description of time-dependent phenomena such as source or detector movement, and source decay kinetics. This feature makes it possible to simulate time curves under realistic acquisition conditions and to test dynamic reconstruction algorithms. This paper gives a detailed description of the design and development of GATE by the OpenGATE collaboration, whose continuing objective is to improve, document and validate GATE by simulating commercially available imaging systems for PET and SPECT. Large effort is also invested in the ability and the flexibility to model novel detection systems or systems still under design. A public release of GATE licensed under the GNU Lesser General Public License can be downloaded at http:/www-lphe.epfl.ch/GATE/. Two benchmarks developed for PET and SPECT to test the installation of GATE and to serve as a tutorial for the users are presented. Extensive validation of the GATE simulation platform has been started, comparing simulations and measurements on commercially available acquisition systems. References to those results are listed. The future prospects towards the gridification of GATE and its extension to other domains such as dosimetry are also discussed.

High-resolution 3D Bayesian image reconstruction using the microPET small-animal scanner

A Bayesian method is described for reconstruction of high-resolution 3D images from the microPET small-animal scanner. Resolution recovery is achieved by explicitly modelling the depth dependent geometric sensitivity for each voxel in combination with an accurate detector response model that includes factors due to photon pair non-collinearity and inter-crystal scatter and penetration. To reduce storage and computational costs we use a factored matrix in which the detector response is modelled using a sinogram blurring kernel. Maximum a posteriori (MAP) images are reconstructed using this model in combination with a Poisson likelihood function and a Gibbs prior on the image. Reconstructions obtained from point source data using the accurate system model demonstrate a potential for near-isotropic FWHM resolution of approximately 1.2 mm at the center of the field of view compared with approximately 2 mm when using an analytic 3D reprojection (3DRP) method with a ramp filter. These results also show the ability of the accurate system model to compensate for resolution loss due to crystal penetration producing nearly constant radial FWHM resolution of 1 mm out to a 4 mm radius. Studies with a point source in a uniform cylinder indicate that as the resolution of the image is reduced to control noise propagation the resolution obtained using the accurate system model is superior to that obtained using 3DRP at matched background noise levels. Additional studies using pie phantoms with hot and cold cylinders of diameter 1-2.5 mm and 18FDG animal studies appear to confirm this observation.

Tomographic bioluminescence imaging by use of a combined optical-PET (OPET) system: a computer simulation feasibility study

The feasibility and limits in performing tomographic bioluminescence imaging with a combined optical-PET (OPET) system were explored by simulating its image formation process. A micro-MRI based virtual mouse phantom was assigned appropriate tissue optical properties to each of its segmented internal organs at wavelengths spanning the emission spectrum of the firefly luciferase at 37 degrees C. The TOAST finite-element code was employed to simulate the diffuse transport of photons emitted from bioluminescence sources in the mouse. OPET measurements were simulated for single-point, two-point and distributed bioluminescence sources located in different organs such as the liver, the kidneys and the gut. An expectation maximization code was employed to recover the intensity and location of these simulated sources. It was found that spectrally resolved measurements were necessary in order to perform tomographic bioluminescence imaging. The true location of emission sources could be recovered if the mouse background optical properties were known a priori. The assumption of a homogeneous optical property background proved inadequate for describing photon transport in optically heterogeneous tissues and led to inaccurate source localization in the reconstructed images. The simulation results pointed out specific methodological challenges that need to be addressed before a practical implementation of OPET-based bioluminescence tomography is achieved.

Digimouse: a 3D whole body mouse atlas from CT and cryosection data

We have constructed a three-dimensional (3D) whole body mouse atlas from coregistered x-ray CT and cryosection data of a normal nude male mouse. High quality PET, x-ray CT and cryosection images were acquired post mortem from a single mouse placed in a stereotactic frame with fiducial markers visible in all three modalities. The image data were coregistered to a common coordinate system using the fiducials and resampled to an isotropic 0.1 mm voxel size. Using interactive editing tools we segmented and labelled whole brain, cerebrum, cerebellum, olfactory bulbs, striatum, medulla, masseter muscles, eyes, lachrymal glands, heart, lungs, liver, stomach, spleen, pancreas, adrenal glands, kidneys, testes, bladder, skeleton and skin surface. The final atlas consists of the 3D volume, in which the voxels are labelled to define the anatomical structures listed above, with coregistered PET, x-ray CT and cryosection images. To illustrate use of the atlas we include simulations of 3D bioluminescence and PET image reconstruction. Optical scatter and absorption values are assigned to each organ to simulate realistic photon transport within the animal for bioluminescence imaging. Similarly, 511 keV photon attenuation values are assigned to each structure in the atlas to simulate realistic photon attenuation in PET. The Digimouse atlas and data are available at http://neuroimage.usc.edu/Digimouse.html.

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.

Molecular imaging of small animals with dedicated PET tomographs.

Abstract. Biological discovery has moved at an accelerated pace in recent years, with a considerable focus on the transition from in vitro to in vivo models. As a result, there has been a significant increase in the need to adapt clinical imaging methods, as well as for novel imaging technologies for biological research. Positron emission tomography (PET) is a clinical imaging modality that permits the use of positron-labeled molecular imaging probes for non-invasive assays of biochemical processes. The imaging procedure can be repeatedly performed before and after interventions, thereby allowing each animal to be used as its own control. Positron-labeled compounds that target a range of molecular targets have been and continue to be synthesized, with examples of biological processes ranging from receptors and synthesis of transmitters in cell communication, to metabolic processes and gene expression. In animal research, PET has been used extensively in the past for studies of non-human primates and other larger animals. New detector technology has improved spatial resolution, and has made possible PET scanning for the study of the most important modern molecular biology model, the laboratory mouse. This paper presents the challenges facing PET technology as applied to small animal imaging, provides a historical overview of the development of small animal PET systems, and discusses the current state of the art in small animal PET technology.

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.

Attenuation correction for small animal PET tomographs

Attenuation correction is one of the important corrections required for quantitative positron emission tomography (PET). This work will compare the quantitative accuracy of attenuation correction using a simple global scale factor with traditional transmission-based methods acquired either with a small animal PET or a small animal x-ray computed tomography (CT) scanner. Two phantoms (one mouse-sized and one rat-sized) and two animal subjects (one mouse and one rat) were scanned in CTI Concorde Microsystems microPET Focus for emission and transmission data and in ImTeks MicroCAT II for transmission data. PET emission image values were calibrated against a scintillation well counter. Results indicate that the scale factor method of attenuation correction places the average measured activity concentration about the expected value, without correcting for the cupping artefact from attenuation. Noise analysis in the phantom studies with the PET-based method shows that noise in the transmission data increases the noise in the corrected emission data. The CT-based method was accurate and delivered low-noise images suitable for both PET data correction and PET tracer localization.

Comparison of 3-D maximum a posteriori and filtered backprojection algorithms for high-resolution animal imaging with microPET

The authors have evaluated the performance of two three-dimensional (3-D) reconstruction algorithms with data acquired from microPET, a high resolution tomograph dedicated to small animal imaging. The first was a linear filtered-backprojection algorithm (FBP) with reprojection of the missing data, and the second was a statistical maximum a posteriori probability algorithm (MAP). The two algorithms were evaluated in terms of their resolution performance, both in phantoms and in vivo. Sixty independent realizations of a phantom simulating the brain of a baby monkey were acquired, each containing three million counts. Each of these realizations was reconstructed independently with both algorithms. The ensemble of the 60 reconstructed realizations was used to estimate the standard deviation as a measure of the noise for each reconstruction algorithm. More detail was recovered in the MAP reconstruction without an increase in noise relative to FBP. Studies in a simple cylindrical compartment phantom demonstrated improved recovery of known activity ratios with MAP. Finally, in vivo studies also demonstrated a clear improvement in spatial resolution using the MAP algorithm. The quantitative accuracy of the MAP reconstruction was also evaluated by comparison with autoradiography and direct well counting of tissue samples and was shown to be superior.