This research program calls for an intensive development and quantitation of a new technology for noninvasive measurements of hemoglobin/myoglobin deoxygenation in skeletal and cardiac muscle. A continuous light method (CWS) is base upon the dual wavelength spectrophotometry principle and can be attached directly to the limb of the exercising animal or human subject. This instrument is a """"""""trend indicator"""""""" and is calibrated in relation to cuff ischemia and hyperemia where possible. The optical path is unknown and only relative responses are obtained with human subjects with peripheral vascular disease or congestive heart failure. The results can be closely correlated with those obtained by phosphorus magnetic resonance spectroscopy. In order to improve quantitation by direct measurement of the optical path, time resolved spectroscopy (TRS) involving picosecond or phase modulation spectroscopy (PMS) technologies afford a quantitation of concentration changes for a single wavelength device and direct measurements of concentrations and their changes for a dual and multi- wavelength animal models in normoxic and ischemic limbs. Furthermore, the separate contributions of Hb/Mb will be evaluated by 1) chemical modification of myoglobin, 2) highly resolved laser spectroscopy, 3) synchronization of hemoglobin signals with the arteriolar pulse, and 4) freeze trapping and redox scanning at low temperatures. The imaging potential of TRS will be studied in models, in normal animals and in limbs with an induced compartment syndrome and in model infarcts of the myocardium using single channel CWS and PMS. Upgrading PMS and TRS to multichannel spectroscopy of these models will provide the data sets which can be analyzed by appropriate algorithms by which the imaging potential can be evaluated with the ultimate goal providing a 3-D motion picture of Hb/Mb changes over the contraction cycle. The hypoxic tissue volume of each model will be evaluated by freeze trapping and 3-D redox scanning under other support. Observations through the chest wall will be attempted where synchrony with systole-distole may afford identification of myocardial tissue volumes, with an end in view of providing methods applicable to human subjects. Thus safe, economical and efficient evaluation of muscle hypoxia/ischemia may become generally available to general and speciality medical evaluations without the use of large magnets or radioactive materials.
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