The overall goal of this research is to examine and understand the morphologic changes that occur in the lung in vivo during the asthmatic episode. We propose to exploit the rapidly developing field of MR microscopy to help delineate macro- and micro-scopic structures in the lung of one animal model of asthma - the guinea pig. The proposal is divided into two parallel components; 1) technical and 2) biological. 1. The technical developments will focus first on improving our MR techniques to allow 3 dimensional imaging of the upper airways. This will be followed by development of methods to characterize small airways on the basis of their impact on MR relaxation parameters T2, T2*, and/or T2'. 2. Biological attention will focus in the first year on measuring the upper airways in vivo in the guinea pig since this model is compatible with our existing animal support system and is an established model of asthma. The second and third year of the proposal will extend work from this model into the smaller, more difficult imaging model of asthma - that utilizing the mouse. The work proposed here will yield benefits in three basic areas: 1) We will clearly attain new information in the correlation of morphometric patterns of asthma and their relation to this devastating lung disease. 2) We will develop animal support and imaging tools useful for studying an even wider range of lung diseases. 3) We will lay the foundation for extending these studies directly to drug discovery and validation of their effectiveness.
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