We propose to analyze the quantitative capability of a camera-based, multi-slice, rotating, single photon emmission computed tomograph (SPECT). A major objective is to demonstrate that precise in vivo SPECT measurements of local radionuclide concentrations can be obtained in physiologic systems possessing a sufficiently slow radiopharmaceutical rate of change to yield quantitatively accurate values within specific anatomical regions. ALterations in SPECT measured radiopharmaceutical distribution in response to selected interventional procedures will be evaluated. Mathematical analysis and computer simulation techniques will be used to characterize the physiological models and SPECT system, resulting in appropriate data processing algorithms for extracting physiologic parameters and compensating for photon attenuation, inclusion of Compton scattered photons and the finite spatial resolution of the SPECT system. An interactive computer facility will be implemented which is capable of the following: 1) supporting the development of the analytic procedure, 2) rapidly displaying, storing and retrieving regional quantitative SPECT data and 3) calculating regional physiologic parameters. The statistical and physiologic significance of these parameters will be evaluated by studies in animals and patients over a five year period. Radiopharmaceuticals labeled with readily available radioisotopes not requiring expensive on-site production facilities are to be utilized: iodine-123 labeled hydroxy-iodinated-phenyl-diamine (HIPD) for the brain stidies, thallium-201 and technetium-99m labeled pyrophosphate for the heart studies, and technetium 99m labeled microspheres for the lung. Technetium-99m labeled microspheres are also to be used to validate SPECT quantitative measurements in the brain and heart. The quantitative precision of SPECT data will be characterized using in vitro models containing known concentrations and volumes of radionuclide. In vivo validation of the technique will be made using animal models and SPECT data obtained with baboons, calves and dogs.
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