Hyperpolarized Xe MR imaging of alveolar gas uptake in humans

Abstract

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.

Conflict of interest statement

Competing Interests: BD receives royalties for several patents related to hyperpolarized gas MRI and received consulting fees from GE Healthcare. JW is an employee of GE Healthcare. The stated competing interest will in no way alter the authors' adherence to all of the PLoS ONE policies on sharing data and materials.

Figures

Figure 1. HP 129Xe MR signal intensity in human lungs.

(A) NMR spectrum obtained using a hard, 7° RF pulse. The gaseous HP 129Xe signal is used as a 0 ppm reference. (B) Spectrum from a selective, 7° pulse centered at 218 ppm. The 218-ppm peak arises from 129Xe dissolved in the red blood cells (RBC), and the 197-ppm arises from 129Xe in the blood plasma and semi-solid parenchymal tissues. (C) Dissolved HP 129Xe signal dynamics during single breath-hold radial imaging. Data points represent the magnitude of k-zero from each radial view weighted by the initial HP 129Xe polarization (P). Even using a relatively large flip angle of α∼17° and a rapid TR of 4.2 ms, substantial dissolved signal is still observed at the end of the breath-hold period due to rapid, diffusive replenishment of dissolved 129Xe magnetization.

Figure 2. HP 129Xe MR imaging.

Panels are arranged with the more anterior portions of the lungs shown to the left and posterior portions to the right. (A) 15-mm-thick sections from a dissolved-phase HP 129Xe image (12.5×12.5 mm2 in-plane resolution) of a healthy human volunteer. (B) Corresponding 15-mm-thick slices from a gas-phase HP 129Xe image of the same subject (3.2×3.2 mm2 in-plane resolution). (C) Dissolved 129Xe image from (A) displayed in color and overlaid on the grayscale ventilation image from (B).

Figure 3. Off-resonant excitation of gas-phase 129Xe magnetization.

(A) Representative 15-mm-thick section from a standard dissolved HP 129Xe image (α = 8°, RF centered 3826 Hz above the gas-phase resonance) of a supine subject. (B) Corresponding 15-mm-thick section from a control image of the same supine subject. The MRI acquisition parameters were identical to those used to produce the image in (A) except that the RF pulse was centered 3826 Hz below the gas-phase resonance. Windowing and leveling were identical for both (A) and (B).

Figure 4. Postural dissolved HP 129Xe image heterogeneity.

Dissolved 129Xe images displayed in grayscale (top) and overlaid in color (bottom) on the corresponding ventilation images. For the color overlays, the dissolved image signal intensity (arbitrary units) is indicated in the legend. The ventilation image was obtained in the supine position. (A) Dissolved image acquired after the subject had been supine for 1 hour. Note, the more gravitationally dependent, posterior portions of the lungs exhibited higher signal intensities than did the less dependent anterior regions. (B) Same subject imaged 10 minutes after moving to the prone position. Again, the gravitationally dependent (now anterior) regions display increased signal intensity.