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Background  One of the central physiological functions of the lungs is to transfer inhaled gases from the alveoli to pulmonary capillary blood. However, current measures of alveolar gas uptake provide only global information and thus lack the sensitivity and specificity needed to account for regional variations in gas exchange.    Methods and Principal Findings  Here we exploit the solubility, high magnetic resonance (MR) signal intensity, and large chemical shift of hyperpolarized (HP)  129 Xe to probe the regional uptake of alveolar gases by directly imaging HP  129 Xe dissolved in the gas exchange tissues and pulmonary capillary blood of human subjects. The resulting single breath-hold, three-dimensional MR images are optimized using millisecond repetition times and high flip angle radio-frequency pulses, because the dissolved HP  129 Xe magnetization is rapidly replenished by diffusive exchange with alveolar  129 Xe. The dissolved HP  129 Xe MR images display significant, directional heterogeneity, with increased signal intensity observed from the gravity-dependent portions of the lungs.    Conclusions  The features observed in dissolved-phase  129 Xe MR images are consistent with gravity-dependent lung deformation, which produces increased ventilation, reduced alveolar size (i.e., higher surface-to-volume ratios), higher tissue densities, and increased perfusion in the dependent portions of the lungs. Thus, these results suggest that dissolved HP  129 Xe imaging reports on pulmonary function at a fundamental level.

Hyperpolarized 129Xe MR Imaging of Alveolar Gas Uptake in Humans