This program project is aimed at bringing an emerging technology, which permits the measurement of pO2 in viable biological systems, to bear on several areas of research which will benefit significantly from the availability of such measurements, and to develop the technology to facilitate its adoption by other scientists for experimental and potential clinical uses. The new technology, which uses EPR, appears to have a unique capability to make repeated, accurately localized measurements of pO2 in vivo and in isolated organs with the accuracy and sensitivity needed for the study of many oxygen-dependent physiological and pathophysiological phenomena. The rationale for carrying out these studies in a program project is based both on the efficiency and effectiveness that this approach adds for the measurements in the components which apply this technology, and the positive effect that this association will have on the further development of the technology. As a consequence, the successful attainment of the goals of this project should result in the widespread availability of an important new experimental capability as well as in the attainment of significant progress in a number of specific areas of research. The component project directed by the PI will provide the technical expertise and equipment needed to make the measurements of pO2, and will carry out the studies in biological systems needed to characterize and calibrate the paramagnetic materials used for the measurements of pO2 and to evaluate their interactions with the biological systems. It also will undertake the further development and optimization of paramagnetic agents and techniques for the measurement of pO2 in viable biological systems, including developments and background information which will facilitate the adoption of these techniques for use with patients. A component at the University of Illinois (Clarkson) provides unique strengths in the development and physical-chemical characterization of paramagnetic probes to be used in the applications. These components will provide support for 3 component projects at Dartmouth in order to understand: 1. the relationship between tissue pO2, MRI (including perfusion/diffusion weighted images), and high resolution 31p NMR spectra of metabolic intermediates in tumors and in the CNS under baseline conditions and during and after acute ischemia; 2. the role of pO2 in radiation induced myelopathy and the effect of therapeutic interventions; 3. the relationship of pO2 in organs (kidney, heart, and hypothalamic and cortical areas of brain) to the markedly different responses to chronic hypoxia of two strains of rats.
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