The broad objective proposed here is to develop and test a magnetic resonance (MR) method that allows functional evaluation of the lung acinar structures by measuring gas exchange. To enhance the signal, the technique uses laser-polarized (129)Xe. Laser polarization increases the signal over thermal (129)Xe by a factor of 10(4)- 10(5). (129)Xe is chosen because it is more than ten times more soluble in tissue than the remaining choice, (3)He, and because the spectral peaks from the gas and dissolved in tissue phases are separated by -200/ppm. This makes the observation of both phases easily observable. The investigators propose to measure the gas exchange rate in acinar structures by observing the relaxation recovery rate of the spectral peaks. The investigators propose to saturate the signal in the tissue (dissolved) phase and observe the signal in this phase due to exchange from the gas spaces. During the 1st year, MR methods will be optimized in phantoms and then rats, where a ventilator will be used to control the lung volume to determine if the exchange is proportional to the lung surface area, which is related to lung volume. Trial experiments on humans will be performed in the 2nd year. The surface of the alveolar septa is the site of gas exchange; its quantification in terms of the local surface to volume ratio is an important determinant of the efficiency of the lung. Derangements at this level include loss of area in destructive diseases such as emphysema, as well as thickening of the blood/gas barrier in interstitial diseases such as pulmonary fibrosis and edema. A major gap in clinical medicine is the failure of all current techniques to evaluate this important parameter noninvasively, or even in vivo. Gas exchange imaging represents a radically new potential for noninvasive evaluation of regional differences in pulmonary function. Early detection of the loss of alveolar surface area is a serious public health imperative, since chronic obstructive pulmonary disease is now the Th leading cause of death in the US.
