OXYGEN MEASUREMENTS IN VIVO BY PHOSPHORESCENCE QUENCHING

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DESCRIPTION: The investigators propose a program to develop reliable methods based on phosphorescence quenching for the measurement of oxygen concentrations in living animals and superficial tissue volumes in human patients, as further described by their abstract: "Oxygen dependent quenching of phosphorescence is a non invasive, highly accurate, optical method for measuring oxygen, including under conditions for which there are either no other suitable method or the existing methods are inadequate. This is new technology which is badly needed in biomedical research and as a diagnostic tool in the clinics, because it can be used non invasive, real time, measurements of tissue oxygenation under physiological conditions and in real time. In order to bring this new technology to its full potential and to make it accessible to a maximum number of users, we will: 1. Design and synthesize water soluble, non-toxic phosphors which absorb and phosphoresce in the near infra red 'window' of tissue. A. Determine the role of the phosphor microenvironment on the oxygen quenching process, e.g. access of oxygen to the phosphor, dependence on pH and temperature, photochemical stability, etc.; B. Determine the chemical properties which control permeability of the phosphors through the vascular wall (leakage into the intravascular space) and of excretion by the kidney. 2. Develop new, high performance, frequency domain phosphorometers for measuring oxygen pressure in vivo. 3. Develop the mathematical formalism needed for extraction of oxygen distributions (histograms) for the microvasculature by computational analysis of the measured phosphorescence decays. 4. Construct and test new optical systems capable of providing 3D maps, at millimeter resolution, of regions of relative hypoxia in tissue volumes several centimeters on a side. "Potential clinical applications include diagnosis and clinical evaluation of complications of diabetes, peripheral vascular disease, cerebrovascular and cardiovascular events as well as detection and therapy design for treatment of tumors."