The objective of this research is the construction of an integrated mathematical model of lung vascular function. We will concentrate on models of the distribution and dynamics of lung blood flow and pressure, the exchange of macromolecules and the filtration of fluids across the lung endothelial barrier, the transport of small molecules and tracers into and across endothelial barriers, including the multiple indicator-dilution method, and transport across in vitro cultured endothelial barriers. Our work will devise mathematical methods which integrate these functions in a single lung. In addition we will use the principles of dynamic similarity to find the specific transport relationships between in vitro cultured endothelial barriers, isolated perfused mammalian lungs, the lungs of intact animals and human lungs. Fractal analysis will be used to study the degree of self similarity within the lung vascular tree. A system of parameters, model choices and analytical tools will be assembled and integrated with a menu driven control operating system. Computer visualization techniques for reverse imaging will be explored. In this method, a model is used to generate a functional image of the lung instead of the 'usual reverse process for acquiring experimental images and attempting to model them. We will examine the combination of this method with more traditional gamma imaging of the lung in order to 'determine its potential for the development of functional imaging. Other visualization methods will be developed to allow presentation of the model predictions in three dimensions, with rotation and with ',,time variable animation. New techniques relying on the creation of novel surfaces will be examined. Similarity studies will concentrate on the identification of scaling variables and dimensionless groups ',which simplify differences and highlight similarities among the transport functions of cultured !endothelial barriers, mammalian lung systems and human lungs. These concepts will be tested with data currently available from our laboratory and from the literature. Through horizontal integration of several kinds of lung vascular function and vertical integration among levels of biological complexity, This research will provide a new system for the analysis of experimental data and simulation of lung 'function. This system should significantly enhance the ability of lung scientists to perform analysis of lung vascular data, simulate a variety of complex interactions in the lung, extrapolate experimental findings to behavior of the human lung and perform experimental designs through simulation of lung vascular function.
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