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Ultra-high-resolution small-animal SPECT imaging

The main subject of this thesis is the development of the first two in a series of dedicated ultra-high resolution Single Photon Emission Computed Tomography (SPECT) systems (U-SPECT-I and II) for the imaging of distributions of radio-isotope labeled tracers in small laboratory animals such as mice and rats. After an explanation of the history of pinhole imaging and the basics of modern reconstruction methods, a possible design for a clinical cardiac SPECT scanner based on focusing pinhole gamma cameras is presented. Calculations demonstrate that it would be possible to increase the sensitivity by an order of magnitude compared to parallel-hole collimation. Since it was unknown to what extent the detrimental effects of pinhole edge penetration and scatter would affect the projection images of a system with smaller pinhole diameters than had been used in any multi-pinhole system before, Monte Carlo simulations were performed to characterize the effects of edge penetration and scatter. These simulations were carried out for multiple isotopes, pinhole diameters, and both for knife-edge and channel pinholes. It is concluded that in a typical imaging situation using the smallest pinhole diameter in use in the U-SPECT scanner, edge penetration amounts to 55% and scatter to 3% of detected photons. Channel edge pinholes do not seem to offer useful advantages over knife-edge pinholes. The more accurately the physical aspects of geometry and photon detection are modelled, the better the reconstructed images will reflect the true distribution of radioactivity. For accuracy, obtaining the system response by direct measurement would be best, but in case of high-resolution instruments this can be impractical to do because of the too high number of required measurement positions. A calibration method was developed that is based on an experimentally determined system response from a limited number of measurements and generalization to the whole object space. The prototype U-SPECT-I system and the second-generation U-SPECT-II system are characterized and initial animal experiments show their imaging capabilities. The U-SPECT system has a reconstructed resolution as determined by the visibility of rods in a micro capillary phantom, of 0.45 mm using 0.6 mm pinholes (mouse), 0.35 mm using 0.3 mm pinholes (mouse), and 0.8 mm using 1.0 mm pinholes (rats). The corresponding peak sensitives are 0.22%, 0.07%, and 0.09% respectively. A resolution below 1 mm is still achievable combined with acquisition times in the order of one minute. Images of a mouse spine show uptake of Tc-99m-hydroxy-methylene diphosphonate (HDP) down to the level of tiny parts of vertebral processes. Using another tracer, myocardial perfusion in the left and right ventricular wall, and even in structures as small as the papillary muscles, can be monitored. The new features in U-SPECT-II include list mode read-out, the ability to also image rats with an easily exchangeable collimator, a more robust design, and an automated method to extend the field-of-view up to total-body imaging. U-SPECT-II is a versatile system for conducting molecular imaging studies and it can be used for novel applications in the study of dynamic biological systems and (radio)pharmaceuticals.