Abstract
In the last few years a need to perform positron emission tomography (PET) studies in small animals has been recognized. These in vivo studies would complement and greatly reduce the number of ex vivo procedures which are currently utilized in the evaluation of putative positron-emitting tracers for clinical use. In addition, they would facilitate the use of animal models of human pathology, providing a unique methodology to serially study regional tissue function in single animals and provide fundamental biological studies to assist in the interpretation of clinical PET data. A dedicated tomographic system with a diameter smaller than for clinical scanners and with detectors of the highest possible spatial resolution has the advantages of higher sensitivity and resolution and, thus, has a potential for non-invasive monitoring of a peripheral arterial input function for human PET studies. This thesis describes the development of a small diameter tomograph incorporating the latest generation of commercial, high resolution multicrystal scintillation detectors. The work involved design and feasibility studies, through to the actual construction and performance evaluation. Initial experiments were performed on a dual block detector system operated at an inter-detector separation of 100 mm. This system incorporated an older generation, bismuth germanate detector with crystal elements of dimension 3.5 mm x 6.25 mm x 30 mm. Physical evaluation of the system indicated that optimal spatial resolutions of 3.6 mm and 4.5 mm full-width at half maximum (FWHM) could be achieved in the two axes of the block. Two-dimensional (2D), dynamic planar imaging, of either rat brain, with positron-emitting radioligands, or the human radial artery with H215O, confirmed the potential of such a system to delineate regional tracer kinetics. Simulations were performed of tomograph designs without inter-plane septa, incorporating either twelve or sixteen of these blocks in ring diameters of 95 mm and 127 mm, respectively. They demonstrated that small ring diameters could provide uniformity of response and high spatial resolution in a small field of view. By using a three-dimensional (3D) filtered-backprojection reconstruction instead of 2D methods, the signal:noise ratio was increased and uniformity maintained. The initial tomographic data, acquired experimentally by rotating the two blocks, confirmed that high spatial resolution was achievable at the centre of the field of view and uptake images of ligand distribution in rat brain illustrated the detail which could be achieved. Uniformity within the field of view was seen to be influenced by detector parallax and normalization. The final, constructed tomograph consisted of sixteen of the latest generation of bismuth germanate PET detector, each with crystal elements of dimension 2.9 mm x 5.9 mm x 30 mm, in a ring diameter of 115 mm, and incorporated standard, commercially available hardware. The detector geometry necessitated novel arrangements for the collection of transmission and normalization data. The performance characteristics of the scanner indicated that a spatial resolution of 2.3 mm and 4.3 mm FWHM was achievable in transaxial and axial directions, respectively, at the centre of the field of view. The scanner geometry, in spite of gaps between detector blocks, resulted in a maximum absolute efficiency of 7.9%. Physical effects of detector sampling and parallax strongly influenced the tomograph response away from the centre of the field of view. Although limited by its off-axis response, biological studies in rat brain verified the potential of the system to acquire reliable kinetic data from radioactivity biodistributions. The data were of sufficient quality to allow the derivation of useful kinetic parameter estimates, using established mathematical models. Overall, the stages involved in the development of the scanner were seen to be fundamentally important to its practical realization. The work encourages further development of small diameter scanners, for use as laboratory tools for biological studies as well as providing an environment for physics research into novel hardware and software implementations. The small diameter tomograph has already proved a useful laboratory tool, being used to acquire in vivo PET data in over 100 animal studies. These studies have ranged from investigations into animal disease models and effects of drug treatments to evaluation of putative positron-emitting tracers for use in humans.