The goal of this proposal is to develop a nanometer-scale resolution computerized tomographic imaging system for small animal and molecular imaging. This will be achieved by building a system designed to work with x-ray compound refractive lenses. Research and development efforts will concentrate on the x-ray source, lens and detector as well as the construction of a prototype to be used and evaluated at the Orthopaedic Research Laboratories of the University of Michigan. Experiments during the first phase of the proposed work demonstrated the utility of the system and a resolution of 1 mu m. A new source will be implemented to provide an order of magnitude more intense, spatially uniform x-ray output over a large area with proper angular and spectral filtering. The aperture of the lenses will be enlarged to increase throughput, decreasing imaging times. A high-resolution imaging x-ray detector will be assembled from available technology. The end-product of the proposed research will be a table-top computerized tomographic imaging system for use in research laboratories using small animal disease models with per frame exposure times of a few seconds. A CT system will be built in Phase II capable of 100 nm resolution, and the technology may eventually achieve 20 nm resolution. This technology will have the ability to image large volumes of tissue and even entire organisms at ultra-fine resolutions, which will generate exciting images of development and disease not possible by current methods. This system can be used for both in-vivo imaging of small animals and ex-vivo imaging of microscopic biological samples. The in-vivo resolution is limited by allowed dose, while sample imaging is limited by the system's capabilities. Given that the proposed technology is x-ray-based, the most immediate impact this technology will be in the morphological evaluation of radiodense tissues, such as calcified and ossified material. Additionally, this technology can potentially be used to interrogate compartments which contain exogenously administered radiodense contrast media, or for microscopic non-invasive imaging such as genetic phenotyping in insects such as Drosophila melanogaster. The nanometer scale CT system resulting from this project should advance research into a wide range of disease entities that present a significant burden to society, including cancer, heart disease, osteoporosis and a wide range of bone disorders. The novel device will help bridge the chasm between the microscopic and clinical world, telling a highly detailed, intriguing story of growth, disease and therapy in a variety of developmental and preclinical models. ? ? ?
