? This proposal is a Shared Instrumentation Grant for a microCT small animal scanner. Our laboratory operates an ultra-high resolution small animal SPECT system, and has a number of active research projects based on this instrument. It has become clear that matching anatomical information is vital to the interpretation and analysis of the functional SPECT data. Indeed, in many applications, the identification of organs and regions on the functional SPECT images is extremely difficult, particularly with such highly specific radiopharmaceuticals. A small animal CT scanner, in conjunction with the SPECT system, would contribute enormously to the research effort of our group by providing anatomical information to complement the functional data. The structural CT images would be used for organ identification, region-of-interest delineation, and to enable improvements to the SPECT data, such as attenuation and partial volume corrections. To enable the accurate registration of anatomical and functional images, the microCT system would have to be located immediately adjacent to the SPECT system to permit easy transfer of anesthetized animals between the two. We have active research projects, which would benefit enormously from the availability of a microCT system to complement the small animal SPECT system, some of which include: 1. Imaging dopaminergic binding sites in the mouse brain, and dual isotope SPECT imaging of the dopaminergic system in hemi-lesioned mice as an animal model of Parkinson's disease. Identification of the mouse brain is difficult based on functional data alone. Gray-white matter differentiation with CT will provide essential anatomical landmarks for localization of brain regions. 2. Imaging the serotonergic system in the mouse brain. This project is studying the interaction of the serotonergic system with antidepressant medication in normal and transgenic mice. 3. Imaging gene transfer and expression in mice. We are using a reporter gene and a SPECT reporter probe system in a study of muscle-directed gene transfer. Identification of the transfected muscle currently is based purely on the localized uptake of the tracer - a much more accurate method would utilize structural data from the microCT. 4. Imaging tumors implanted in mice. The over expression of sigma-2 receptors in certain tumors is a valuable marker of cell proliferation. However, identification of tumor boundaries is difficult without structural data, particularly in regions of tumor necrosis. In conclusion, a microCT system would provide essential structural data to complement functional SPECT data in small animals, and will greatly strengthen the quantitative aspects of this emerging molecular imaging technique. ? ?
