BackgroundOne 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 FindingsHere we exploit the solubility, high magnetic resonance (MR) signal intensity, and large chemical shift of hyperpolarized (HP) 129Xe to probe the regional uptake of alveolar gases by directly imaging HP 129Xe 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 129Xe magnetization is rapidly replenished by diffusive exchange with alveolar 129Xe. The dissolved HP 129Xe MR images display significant, directional heterogeneity, with increased signal intensity observed from the gravity-dependent portions of the lungs.ConclusionsThe features observed in dissolved-phase 129Xe 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 129Xe imaging reports on pulmonary function at a fundamental level.

Purpose:To evaluate the safety and tolerability of inhaling multiple 1-L volumes of undiluted hyperpolarized xenon 129 ( 129 Xe) followed by up to a 16-second breath hold and magnetic resonance (MR) imaging. Materials and Methods:This study was approved by the institutional review board and was HIPAA compliant. Written informed consent was obtained. Forty-four subjects (19 men, 25 women; mean age, 46.1 years 6 18.8 [standard deviation ]) were enrolled, consisting of 24 healthy volunteers, 10 patients with chronic obstructive pulmonary disease (COPD), and 10 age-matched control subjects. All subjects received three or four 1-L volumes of undiluted hyperpolarized 129 Xe, followed by breath-hold MR imaging. Oxygen saturation, heart rate and rhythm, and blood pressure were continuously monitored. These parameters, along with respiratory rate and subjective symptoms, were assessed after each dose. Subjects' serum biochemistry and hematology were recorded at screening and at 24-hour follow-up. A 12-lead electrocardiogram (ECG) was obtained at these times and also within 2 hours prior to and 1 hour after 129 Xe MR imaging. Xenon-related symptoms were evaluated for relationship to subject group by using a x 2 test and to subject age by using logistic regression. Changes in vital signs were tested for signifi cance across subject group and time by using a repeated-measures multivariate analysis of variance test.

Purpose We sought to develop and test a clinically feasible 1-point Dixon, 3D radial acquisition strategy to create isotropic 3D MR images of 129Xe in the airspaces, barrier, and red blood cells (RBCs) in a single breath. The approach was evaluated in healthy volunteers and subjects with idiopathic pulmonary fibrosis (IPF). Methods A calibration scan determined the TE at which 129Xe in RBCs and barrier were 90° out of phase. At this TE, interleaved dissolved and gas-phase images were acquired using a 3D radial acquisition and were reconstructed separately using the NUFFT algorithm. The dissolved-phase image was phase-shifted to cast RBC and barrier signal into the real and imaginary channels such that the image-derived RBC:barrier ratio matched that from spectroscopy. The RBC and barrier images were further corrected for regional field inhomogeneity using a phase map created from the gas-phase 129Xe image. Results Healthy volunteers exhibited largely uniform 129Xe-barrier and 129Xe-RBC images. By contrast, 129Xe-RBC images in IPF subjects exhibited significant signal voids. These voids correlated qualitatively with regions of fibrosis visible on CT. Conclusions This study illustrates the feasibility of acquiring single-breath, 3D isotropic images of 129Xe in the airspaces, barrier, and RBCs using a 1-point Dixon 3D radial acquisition.

Purpose We sought to develop and test a clinically feasible 1‐point Dixon, three‐dimensional (3D) radial acquisition strategy to create isotropic 3D MR images of 129Xe in the airspaces, barrier, and red blood cells (RBCs) in a single breath. The approach was evaluated in healthy volunteers and subjects with idiopathic pulmonary fibrosis (IPF). Methods A calibration scan determined the echo time at which 129Xe in RBCs and barrier were 90° out of phase. At this TE, interleaved dissolved and gas‐phase images were acquired using a 3D radial acquisition and were reconstructed separately using the NUFFT algorithm. The dissolved‐phase image was phase‐shifted to cast RBC and barrier signal into the real and imaginary channels such that the image‐derived RBC:barrier ratio matched that from spectroscopy. The RBC and barrier images were further corrected for regional field inhomogeneity using a phase map created from the gas‐phase 129Xe image. Results Healthy volunteers exhibited largely uniform 129Xe‐barrier and 129Xe‐RBC images. By contrast, 129Xe‐RBC images in IPF subjects exhibited significant signal voids. These voids correlated qualitatively with regions of fibrosis visible on CT. Conclusions This study illustrates the feasibility of acquiring single‐breath, 3D isotropic images of 129Xe in the airspaces, barrier, and RBCs using a 1‐point Dixon 3D radial acquisition. Magn Reson Med 75:1434–1443, 2016. © 2015 Wiley Periodicals, Inc.

Although some central aspects of pulmonary function (ventilation and perfusion) are known to be heterogeneous, the distribution of diffusive gas exchange remains poorly characterized. A solution is offered by hyperpolarized 129Xe magnetic resonance (MR) imaging, because this gas can be separately detected in the lung's air spaces and dissolved in its tissues. Early dissolved-phase 129Xe images exhibited intensity gradients that favored the dependent lung. To quantitatively corroborate this finding, we developed an interleaved, three-dimensional radial sequence to image the gaseous and dissolved 129Xe distributions in the same breath. These images were normalized and divided to calculate "129Xe gas-transfer" maps. We hypothesized that, for healthy volunteers, 129Xe gas-transfer maps would retain the previously observed posture-dependent gradients. This was tested in nine subjects: when the subjects were supine, 129Xe gas transfer exhibited a posterior-anterior gradient of -2.00 ± 0.74%/cm; when the subjects were prone, the gradient reversed to 1.94 ± 1.14%/cm (P < 0.001). The 129Xe gas-transfer maps also exhibited significant heterogeneity, as measured by the coefficient of variation, that correlated with subject total lung capacity (r = 0.77, P = 0.015). Gas-transfer intensity varied nonmonotonically with slice position and increased in slices proximal to the main pulmonary arteries. Despite substantial heterogeneity, the mean gas transfer for all subjects was 1.00 ± 0.01 while supine and 1.01 ± 0.01 while prone (P = 0.25), indicating good "matching" between gas- and dissolved-phase distributions. This study demonstrates that single-breath gas- and dissolved-phase 129Xe MR imaging yields 129Xe gas-transfer maps that are sensitive to altered gas exchange caused by differences in lung inflation and posture.