We have developed a knowledge-based approach to analyzing dynamic nuclear medicine data sets using factor analysis. Prior knowledge is used as constraints to produce factor images and their associated time functions which are physically and physiologically realistic. These methods have been applied to both planar and tomographic image sequences acquired using various single-photon emitting and positron emitting radiotracers. Computer-simulated data, non-human primate studies, and human clinical studies have been used to develop and evaluate the methodology. The organ systems studied include the kidneys, heart, brain, liver, and bone. The factors generated represent various isolated aspects of physiologic function, such as tissue perfusion and clearance. In some clinical studies, the factors have indicated the potential to isolate diseased tissue from normally functioning tissue. In addition, the factor analysis of data acquired using newly developed radioligands has shown the ability to differentiate the specific binding of the radioligand to the targeted receptors from the non-specific binding. This suggests the potential use of factor analysis in the development and evaluation of radiolabeled compounds as well as in the investigation of specific receptor systems and their role in diagnosing disease.
In victims of electrical trauma, electroporation of cell membrane, in which lipid bilayer is permeabilized by thermal and electrical forces, is thought to be a substantial cause of tissue damage. It has been suggested that certain mild surfactant in low concentration could induce sealing of permeabilized lipid bilayers, thus repairing cell membranes that had not been extensively damaged. With an animal model of electrically injured hind limb of rats, we have demonstrated and validated the use of radiotracer imaging technique to assess the physiology of the damaged tissues after electrical shock and of their repairs after applying surfactant as a therapeutic strategy. For example, using Tc-99m labeled pyrophosphate (PYP), which follows calcium in cellular function and is known to accumulate in damaged tissues, we have established a physiological imaging approach for assessment of the extent of tissue injury for diagnosis and surgical planning, as well as for evaluation of responses to therapy. With the use of a small, hand-held, miniature gamma camera, this physiological imaging method can be employed at patient's bedside and even in the field, for example, at accident site or during transfer for emergency care, rapid diagnosis, and prompt treatment in order to maximize the chance for tissue survival.
In a two-compartment scintillation vial, suspensions of bacteria were cultured with 1 muCi of [U-14C] glucose and the released 14C02 was measured continuously, cumulatively, and automatically in a liquid-scintillation counter modified to maintain sample temperature at 37 degrees C. We could follow the metabolism of bacterial populations through their early phase of exponential growth with good precision. The data were obtained conveniently, with use of conventional reagents, glassware, and counting equipment. From analysis of the exponential portion of the curves for cumulative activity vs. time, we could measure cell replication rate precisely in units of time. The resulting values were demonstrably independent of some common experimental variables, including the number of bacteria in the inoculum and counting system sensitivity. Sensitivity of the bacteria to antibiotics was measured to within a few percent by noting the relative prolongation of replication time in the presence of those inhibitors. The digital data from the scintillation counter are susceptible to on- or off-line computer analysis, thus providing the prospect for a totally-automated analytical system. The method shows promise for the mechanized quantitative analysis of bacterial growth, and its inhibition.
In a two-compartment scintillation vial, suspensions of bacteria were cultured with 1 ..mu..Ci of (U-/sup 14/C) glucose and the released /sup 14/CO/sub 2/ was measured continuously, cumulatively, and automatically in a liquid-scintillation counter modified to maintain sample temperature at 37/sup 0/C. The metabolism of bacterial populations were followed through their early phase of exponential growth with good precision. The data were obtained conveniently, with use of conventional reagents, glassware, and counting equipment. From analysis of the exponential portion of the curves for cumulative activity vs. time, cell replication rate could be measured precisely in units of time. The resulting values were demonstrably independent of some common experimental variables, including the number of bacteria in the inoculum and counting system sensitivity. Sensitivity of the bacteria to antibiotics was measured to within a few percent by noting the relative prolongation of replication time in the presence of those inhibitors. The digital data from the scintillation counter are susceptible to on- or off-line computer analysis, thus providing the prospect for a totally-automated analytical system. The method shows promise for the mechanized quantitative analysis of bacterial growth, and its inhibition.
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