Validation of a small-animal PET simulation using GAMOS: a Geant4-based framework

onte Carlo-based modelling is a powerful tool to help in the design and optimization of positron emission tomography (PET) systems. The performance of these systems depends on several parameters, such as detector physical characteristics, shielding or electronics, whose effects can be studied on the basis of realistic simulated data. The aim of this paper is to validate a comprehensive study of the Raytest ClearPET small-animal PET scanner using a new Monte Carlo simulation platform which has been developed at CIEMAT (Madrid, Spain), called GAMOS (GEANT4-based Architecture for Medicine-Oriented Simulations). This toolkit, based on the GEANT4 code, was originally designed to cover multiple applications in the field of medical physics from radiotherapy to nuclear medicine, but has since been applied by some of its users in other fields of physics, such as neutron shielding, space physics, high energy physics, etc. Our simulation model includes the relevant characteristics of the ClearPET system, namely, the double layer of scintillator crystals in phoswich configuration, the rotating gantry, the presence of intrinsic radioactivity in the crystals or the storage of single events for an off-line coincidence sorting. Simulated results are contrasted with experimental acquisitions including studies of spatial resolution, sensitivity, scatter fraction and count rates in accordance with the National Electrical Manufacturers Association (NEMA) NU 4-2008 protocol. Spatial resolution results showed a discrepancy between simulated and measured values equal to 8.4% (with a maximum FWHM difference over all measurement directions of 0.5 mm). Sensitivity results differ less than 1% for a 250–750 keV energy window. Simulated and measured count rates agree well within a wide range of activities, including under electronic saturation of the system (the measured peak of total coincidences, for the mouse-sized phantom, was 250.8 kcps reached at 0.95 MBq mL−1 and the simulated peak was 247.1 kcps at 0.87 MBq mL−1). Agreement better than 3% was obtained in the scatter fraction comparison study. We also measured and simulated a mini-Derenzo phantom obtaining images with similar quality using iterative reconstruction methods. We concluded that the overall performance of the simulation showed good agreement with the measured results and validates the GAMOS package for PET applications. Furthermore, its ease of use and flexibility recommends it as an excellent tool to optimize design features or image reconstruction techniques

Three-Dimensional Characterization of the Vascular Bed in Bone Metastasis of the Rat by Microcomputed Tomography (MicroCT)

BackgroundAngiogenesis contributes to proliferation and metastatic dissemination of cancer cells. Anatomy of blood vessels in tumors has been characterized with 2D techniques (histology or angiography). They are not fully representative of the trajectories of vessels throughout the tissues and are not adapted to analyze changes occurring inside the bone marrow cavities. Methodology/Principal Findings We have characterized the vasculature of bone metastases in 3D at different times of evolution of the disease. Metastases were induced in the femur of Wistar rats by a local injection of Walker 256/B cells. Microfil®, (a silicone-based polymer) was injected at euthanasia in the aorta 12, 19 and 26 days after injection of tumor cells. Undecalcified bones (containing the radio opaque vascular casts) were analyzed by microCT, and a first 3D model was reconstructed. Bones were then decalcified and reanalyzed by microCT; a second model (comprising only the vessels) was obtained and overimposed on the former, thus providing a clear visualization of vessel trajectories in the invaded metaphysic allowing quantitative evaluation of the vascular volume and vessel diameter. Histological analysis of the marrow was possible on the decalcified specimens. Walker 256/B cells induced a marked osteolysis with cortical perforations. The metaphysis of invaded bones became progressively hypervascular. New vessels replaced the major central medullar artery coming from the diaphyseal shaft. They sprouted from the periosteum and extended into the metastatic area. The newly formed vessels were irregular in diameter, tortuous with a disorganized architecture. A quantitative analysis of vascular volume indicated that neoangiogenesis increased with the development of the tumor with the appearance of vessels with a larger diameter. Conclusion This new method evidenced the tumor angiogenesis in 3D at different development times of the metastasis growth. Bone and the vascular bed can be identified by a double reconstruction and allowed a quantitative evaluation of angiogenesis upon time

[[alternative]]IEEE Nuclear Science Symposium Conference Record

[[abstract]]The ability to acquire images with resolutions in the micrometer range, as recently reported for pinhole and multipin-hole SPECT systems, raised interest in these imaging modalities within the preclinical small animal imaging research community. At such high resolutions, physical imaging properties such as pinhole edge penetration, detector blur, detector misalignment, the geometric response of the aperture, and gamma photon attenuation and scatter can severely degrade image quality. To improve system design and reconstruction methods, an aperture edge penetration model was developed. The model was simulated in GATE by replacing each imaging detector element with a point source and collecting the photons emitted by this source on the opposite side of the aperture. For efficiency, only one detector quadrant was evaluated and sampling of the model was performed for every fourth detector element. Furthermore, the photons were focused onto the aperture by adjusting the polar and azimuthal emission angles. Models were developed for two imaging systems using 2 different isotopes (Tc99m & I-125). The first system had a detector size of 260 mm and a pinhole-to-detector distance of 180 mm. The second had a detector size of 90 mm and a pinhole-to-detector distance of 100 mm. The same aperture was used for both systems. The system with the larger detector showed an enlargement in effective pinhole size inversely proportional to the distance between detector center and detector element, whereas the smaller detector showed a similar dependence at a reduced amplitude. For I-125, the effective pinhole size was similar to the bore diameter, since only a small number of the low energy photons penetrated through the aperture material. This simulation of the aperture edge penetration will aid in better understanding pinhole SPECT system design that minimize the penetration effects, as well as for development of more accurate reconstruction algorithms

[[alternative]]IEEE Nuclear Science Symposium Conference Record

[[abstract]]Iterative reconstruction of pinhole SPECT projection data acquired in preclinical animal imaging research benefits from modeling physical parameters of the imaging process. In this study, we developed a ray-driven system model that accounts for detector blur, the geometric response and edge penetration of the pinhole. GATE 2.2.0/GEANT 4 Monte Carlo simulations utilizing a tungsten knife-edge pinhole with an aperture diameter of 2 mm were applied to measure the pinhole point spread function (PSF) and to generate pinhole SPECT projection images of 2 different resolution phantoms (2.0 mm and 1.8 mm). The new Monte Carlo based PSF with edge penetration was compared to an ideal pinhole model without edge penetration. To conserve memory, the ray-driven system matrix was computed for one angle and rotation was performed by interpolating the radiotracer distribution within the object space. Detector symmetry and a bitwise incremental storage scheme were utilized for further reduction of memory requirements. Two system setups with a magnification of 7.2x and 2x were studied. Reconstruction results show an improvement in image quality and reconstruction resolution for the new pinhole PSF model. In the low magnification system operated at its resolution limits these improvements are more pronounced than in the high magnification system. The newly implemented ray-driven reconstruction method has great flexibility and offers to be a platform for further improvements such as non-uniform attenuation and scatter correction, and integration of detector misalignments in the system matrix

[[alternative]]2007 IEEE Nuclear Science Symposium and Medical Imaging Conference, NSS-MIC

[[abstract]]Recent improvements in detector technology allow pinhole SPECT to approach spatial resolutions as low as 50 μm. Such high resolutions require a high accuracy of the imaging gantry for preclinical SPECT systems, and is not easily achieved in a laboratory setting. Analytical calibration methods are deemed to fail due to practical implications such as size and activity concentrations of the required point sources. Thus, we have developed a numerical calibration method based on leastsquare optimization that incorporates the modeling attributes of a forward projector frequently used in iterative reconstruction. The forward projector is currently capable of modeling detector misalignment such as detector rotation and pinhole translation, and will incorporate the pinhole point spread function as well as the size and shape of the point source. Currently, our calibration phantom consists of a single point source, positioned off-center in the object space. The optimization method involves a sequentially fitting of each individual parameter to the data, followed by fitting multiple parameters simultaneous in consecutive steps including all five parameters for the final fitting. The results of the optimization show an error of expected magnitude considering the relatively coarse sampling grid of our simulations. The relatively slow convergence of the y- and z-tilt require simulation of additional point sources. Further improvements of computational and memory efficiency need to be made, which enable the method to fit high resolution data as well as incorporation of the pinhole point spread function and the shape and size of the point sources

[[alternative]]Medical Imaging 2006: Physics of Medical Imaging

[[abstract]]Reconstruction methodologies for data sets with reduced angular sampling (RAS) are essential for efficient dynamic or static preclinical animal imaging research using single photon emission computed tomography (SPECT). Modern iterative reconstruction methods can obtain 3D radiotracer distributions of the highest possible quality and resolution. Essential to these algorithms is an accurate model of the physical imaging process. We developed a new point-spread function (PSF) model for the pinhole geometry and compared it to a Gaussian model in a RAS setting. The new model incorporates the geometric response of the pinhole and the detector response of the camera by simulating the system PSF using the error function. Reconstruction of simulated data was done with OS-EM and COS-EM: a new convergent OS-EM based algorithm. The reconstruction of projection data of a simulated point source using the novel method showed improved FWHM values compared to a standard Gaussian method. COS-EM delivers improved results for RAS data, although it converges slower than OS-EM. The reconstruction of Monte Carlo simulated projection data from a resolution phantom shows that as few as 40 projections are sufficient to reconstruct an image with a resolution of approximately 4 mm. The new pinhole model applied to iterative reconstruction methods can reduce imaging time in small animal experiments by a factor of three or reduce the number of cameras needed to perform dynamic SPECT

[[alternative]]Proceedings of the Society of Photo-Optical Instrumentation Engineers (Spie)

[[abstract]]Small animal SPECT using low energy photons of I-125 and approaching resolutions of microscopic levels, imaging parameters such as pinhole edge penetration, detector blur, geometric response, detector and pinhole misalignment, and gamma photon attenuation and scatter can have increasingly noticeable and/or adverse effects on reconstructed image quality. Iterative reconstruction algorithms, the widelyaccepted standard for emission tomography, allow modeling of such parameters through a system matrix. For this Monte Carlo simulation study, non-uniform attenuation correction was added to the existing system model. The model was constructed using ray-tracing and further included corrections for edge penetration, detector blur, and geometric aperture response. For each ray passing through different aperture locations, this method attenuates a voxel's contribution to a detector element along the photon path, which is then weighted according to a pinhole penetration model. To lower the computational and memory expenses, symmetry along the detector axes and an incremental storage scheme for the system model were used. For evaluating the nonuniform attenuation correction method, 3 phantoms were designed of which projection images were simulated using Monte Carlo methods. The first phantom was used to examined skin artifacts, the second to simulate attenuation by bone, and the third to generate artifacts of an air-filled space surrounded by soft tissue. In reconstructions without attenuation correction, artifacts were observed with up to a 40% difference in activity. These could be corrected using the implemented method, although in one case overcorrection occurred. Overall, attenuation correction improved reconstruction accuracy of the radioisotope distribution in the presence of structural differences

3D X-Ray Microtomography Applied to Structural and Mechanical Characterization of Arterial Trees

We applied micro-CT imaging to arterial trees in rodent lungs. Morphometric features derived from the images are sensitive to interspecies differences in vascular structure and can reflect the distensibility of arterial walls

SPECT/Micro-CT Imaging of Bronchial Angiogenesis in a Rat

The bronchial circulation provides the lung with an oxygenated blood supply, derived from the aorta, whose primary purpose under normal conditions is thought to be nourishment of the airway walls +Guyton, 1996-. However,the study of the bronchial circulation and its development is particularly important with regard to lung tumors whose blood supply is via the bronchial circulation rather than the pulmonary circulation +Hirsch, 2001, Ohta, 2002-. Thus, we have developed a rat model of bronchial circulation angiogenesis,induced by complete occlusion of the left pulmonary artery. We have been observing the resulting perfusion changes in the left lung using dual-modality SPECT/micro-CT imaging. The initial objective of this study is to develop the necessary imaging system, protocol, and analysis methods for determining the time course of this angiogenesis, with the subsequent goal of using this approach to study the particular angiogenic mechanisms that might be involved

SPECT/Micro-CT Imaging of Bronchial Angiogenesis in a Rat

The bronchial circulation provides the lung with an oxygenated blood supply, derived from the aorta, whose primary purpose under normal conditions is thought to be nourishment of the airway walls +Guyton, 1996-. However,the study of the bronchial circulation and its development is particularly important with regard to lung tumors whose blood supply is via the bronchial circulation rather than the pulmonary circulation +Hirsch, 2001, Ohta, 2002-. Thus, we have developed a rat model of bronchial circulation angiogenesis,induced by complete occlusion of the left pulmonary artery. We have been observing the resulting perfusion changes in the left lung using dual-modality SPECT/micro-CT imaging. The initial objective of this study is to develop the necessary imaging system, protocol, and analysis methods for determining the time course of this angiogenesis, with the subsequent goal of using this approach to study the particular angiogenic mechanisms that might be involved