We propose continuation of studies of the environmental impact of particulate matter on lung structure and function using in vivo magnetic resonance microscopy. We will expand our previous work with hyperpolarized 3He to support localized three-dimensional structural imaging at 1 x 10-4 mm3. We will extend our physiologic support system and spiral encoding techniques to quantitative flow measurements and functional imaging at 1 x 10-2 mm3. We will study the impact of particulates in three specific models: 1) elastase-induced injury, a model of emphysema; 2) inflammation and remodeling in the endotoxin sensitive C3H/HeBFeJ mouse, a model of organic dust induced asthma; and 3) inflammation and remodeling in the vanadium pentoxide model of asthma, which is characterized by extensive bronchiolar fibrosis. The proposal will refine methods that will be applicable to a much wider range of basic pulmonary studies while obtaining detailed assessment of structural and functional changes in three important models of human disease. By extending the methodologies to the mouse, we will build a critical bridge between man and mouse models of pulmonary disease that will be essential to understanding the pathophysiology of pulmonary disease and the validation of new therapies.
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