Accurate molecular imaging of small animals taking into account animal models, handling, anaesthesia, quality control and imaging system performance

Small-animal imaging has become an important technique for the development of new radiotracers, drugs and therapies. Many laboratories have now a combination of different small-animal imaging systems, which are being used by biologists, pharmacists, medical doctors and physicists. The aim of this paper is to give an overview of the important factors in the design of a small animal, nuclear medicine and imaging experiment. Different experts summarize one specific aspect important for a good design of a small-animal experiment

Characterizing the parallax error in multi-pinhole micro-SPECT reconstruction

The usage of pinholes is very important in preclinical micro-SPECT. Pinholes can magnify the object onto the detector, resulting in better system resolutions than the detector resolution. The loss in sensitivity is usually countered by adding more pinholes, each projecting onto a specific part of the detector. As a result, gamma rays have an oblique incidence to the detector. This causes displacement and increased uncertainty in the position of the interaction of the gamma ray in the detector, also known as parallax errors or depth-of-interaction (DOI) errors. This in turn has a large influence on image reconstruction algorithms using ray tracers as a forward projector model, as the end-point of each ray on the detector has to be accurately known. In this work, we used GATE to simulate the FLEX Triumph-I system (Gamma Medica-Ideas, Northridge, CA), a CZT-based multi-pinhole micro-SPECT system. This system uses 5 mm thick CZT pixels, with 1.5 mm pixel pitch. The simulated information was then used to enhance the image resolution by accurately modeling the DOI. Two hundred point sources were simulated and rebinned to use the DOI information. This data was then used in a GPU-based iterative reconstruction algorithm taking the simulated DOI into account. The average displacement was then determined for all point sources, and the FWHM was calculated in three dimensions, by fitting the point sources with 3D Gaussians. We show that the displacement is reduced by 83% on average. We also show a 15% resolution gain when only 5 DOI levels are used

SPECT Imaging of Pulmonary Blood Flow in a Rat

Small animal imaging is experiencing rapid development due to its importance in providing high-throughput phenotypic data for functional genomics studies. We have developed a single photon emission computed tomography (SPECT) system to image the pulmonary perfusion distribution in the rat. A standard gamma camera, equipped with a pinhole collimator, was used to acquire SPECT projection images at 40 sec/view of the rat thorax following injection of Tc99m labeled albumin that accumulated in the rat\u27s lungs. A voxel-driven, ordered-subset expectation maximization reconstruction was implemented. Following SPECT imaging, the rat was imaged using micro-CT with Feldkamp conebeam reconstruction. The two reconstructed image volumes were fused to provide a structure/function image of the rat thorax. Reconstruction accuracy and performance were evaluated using numerical simulations and actual imaging of an experimental phantom consisting of Tc99m filled chambers with known diameters and count rates. Full-width half-maximum diameter measurement errors decreased with increasing chamber diameter, ranging from \u3c 6% down to 0.1%. Errors in the ratio of count rate estimates between tubes were also diameter dependent but still relatively small. This preliminary study suggests that SPECT will be useful for imaging and quantifying the pulmonary blood flow distribution and the distribution of Tc99m labeled ligands in the lungs of small laboratory animals

Quantification of Bronchial Circulation Perfusion in Rats

The bronchial circulation is thought to be the primary blood supply for pulmonary carcinomas. Thus, we have developed a method for imaging and quantifying changes in perfusion in the rat lung due to development of the bronchial circulation. A dual-modality micro-CT/SPECT system was used to detect change in perfusion in two groups of rats: controls and those with a surgically occluded left pulmonary artery. Both groups were imaged following injections on separate days i) 2mCi of Tc99m labeled macroaggregated albumin (MAA) into the left carotid artery (IA) and ii) a similar injection into the femoral vein (IV). The IA injection resulted in Tc99m accumulation in capillaries of the systemic circulation including the bronchial circulation, whereas the IV resulted in Tc99m accumulation in the pulmonary capillaries. Ordered subset expectation maximization (OSEM) was used to reconstruct the SPECT image volumes and a Feldkamp algorithm was used to reconstruct the micro-CT image volumes. The micro-CT and SPECT volumes were registered, the SPECT image volume was segmented using the right and left lung boundaries defined from the micro-CT volume, and the ratio of IA radioactivity accumulation in the left lung to IV radioactivity accumulation in both lungs was used as a measure of left lung flow via the bronchial circulation. This ratio was ~0.02 for the untreated rats compared to the treated animals that had an increased flow ratio of ~0.21 40 days after left pulmonary artery occlusion. This increase in flow to the occluded left lung via the bronchial circulation suggests this will be a useful model for further investigating antiangiogenic treatments

Quantification of Bronchial Circulation Perfusion in Rats

The bronchial circulation is thought to be the primary blood supply for pulmonary carcinomas. Thus, we have developed a method for imaging and quantifying changes in perfusion in the rat lung due to development of the bronchial circulation. A dual-modality micro-CT/SPECT system was used to detect change in perfusion in two groups of rats: controls and those with a surgically occluded left pulmonary artery. Both groups were imaged following injections on separate days i) 2mCi of Tc99m labeled macroaggregated albumin (MAA) into the left carotid artery (IA) and ii) a similar injection into the femoral vein (IV). The IA injection resulted in Tc99m accumulation in capillaries of the systemic circulation including the bronchial circulation, whereas the IV resulted in Tc99m accumulation in the pulmonary capillaries. Ordered subset expectation maximization (OSEM) was used to reconstruct the SPECT image volumes and a Feldkamp algorithm was used to reconstruct the micro-CT image volumes. The micro-CT and SPECT volumes were registered, the SPECT image volume was segmented using the right and left lung boundaries defined from the micro-CT volume, and the ratio of IA radioactivity accumulation in the left lung to IV radioactivity accumulation in both lungs was used as a measure of left lung flow via the bronchial circulation. This ratio was ~0.02 for the untreated rats compared to the treated animals that had an increased flow ratio of ~0.21 40 days after left pulmonary artery occlusion. This increase in flow to the occluded left lung via the bronchial circulation suggests this will be a useful model for further investigating antiangiogenic treatments

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. A public release of GATE licensed under the GNU Lesser General Public License can be downloaded at the address http://www-lphe.epfl.ch/GATE/