The long-term goal of this research is to define the solid state chemistry of bone mineral at various stages of maturation from the earliest deposition-processes through fully mature bone in adult organisms, and in the various remodeling steps associated with healing and bone-related diseases. Despite many years of research, there is a glaring gap in our knowledge of bone mineral chemistry in normal developing organisms, during the healing of fractures, and in diseases involving bone mineral. Osteoporosis is an example of one such disease which has assumed major proportions as an issue in public health, and women's health in particular. Specifically, we will characterize and attempt to identify the chemical forms of calcium phosphate involved in the earliest new mineral laid down in deposition processes in developing organisms and in a rabbit drill hole model of defect healing. The knowledge we gain is expected to enhance our understanding of the fundamental biological processes involving deposition and resorption of bone, as well as our understanding of bone-related diseases. In order to achieve these goals, we will develop and apply novel solid state (31)P cross polarization magnetic resonance spectroscopy and imaging techniques for the in vitro and in vivo assessment of bone mineral chemistry. The use of solid state MR imaging and spectroscopy of bone, largely unexplored, holds enormous potential for increasing knowledge of bone formation, resorption, growth, and healing, and for following these processes in the body noninvasively. The methods and apparatus we develop will have application also to, and yield similar advantages in, studies of artificial materials and devices, including silicone implants, and polymeric, composite and ceramic prostheses.
The specific aims of the project include 1) refining and validating these solid state MR imaging and spectroscopic techniques to achieve the degree of quantitative accuracy necessary for continuing research on bone mineral development; 2) improving the compatibility of solid state cross polarization imaging and spectroscopy with living subjects; and 3) characterizing early mineral and its maturation in a rabbit tibia drill hole model by in vivo (31)P solid state cross polarization imaging and localized spectroscopy, and ex vivo high field differential cross polarization spectroscopy.
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