Imaging alveolar–capillary gas transfer using hyperpolarized 129 Xe MRI

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Abstract
Effective pulmonary gas exchange relies on the free diffusion of gases across the thin tissue barrier separating airspace from the capillary red blood cells (RBCs). Pulmonary pathologies, such as inflammation, fibrosis, and edema, which cause an increased blood–gas barrier thickness, impair the efficiency of this exchange. However, definitive assessment of such gas-exchange abnormalities is challenging, because no methods currently exist to directly image the gas transfer process. Here we exploit the solubility and chemical shift of 129 Xe, the magnetic resonance signal of which has been enhanced by 10 5 with hyperpolarization, to differentially image its transfer from the airspaces into the tissue barrier spaces and RBCs in the gas exchange regions of the lung. Based on a simple diffusion model, we estimate that this MR imaging method for measuring 129 Xe alveolar-capillary transfer is sensitive to changes in blood–gas barrier thickness of ≈5 μm. We validate the successful separation of tissue barrier and RBC images and show the utility of this method in a rat model of pulmonary fibrosis where 129 Xe replenishment of the RBCs is severely impaired in regions of lung injury.