Hyperpolarized 129Xe MR Imaging of Alveolar Gas Uptake in Humans

Abstract

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.

Simultaneous magnetic resonance imaging of ventilation distribution and gas uptake in the human lung using hyperpolarized xenon-129

“…The distributions of both ventilation and gas uptake were overall spatially uniform in healthy subjects, as expected. Nonetheless, 3D acquisitions revealed a gradient in dissolvedphase signal intensity along the anterior-posterior direction, consistent with the observation of Cleveland et al (13) and likely due to the well-described gravity-dependent gradient in lung tissue density from anterior to posterior in the supine position. Subjects with lung disease showed spatial variations in ventilation, as expected based on published studies using hyperpolarized He3 MRI (14)(15)(16)(17), as well as in gas uptake, although the variations in gas uptake differed from the variations in ventilation in many regions of the lung.…”

“…1, a simultaneous gas-phase-dissolved-phase imaging technique was implemented based on a standard radiofrequency-spoiled gradient-echo pulse sequence. Considering that the signal evolutions depend on the repetition time and flip angles, and that the signal amplitudes may decrease markedly during the course of the acquisition as the hyperpolarized magnetization is depleted (13), sequential, rather than centric, phase-encoding order was used, to reduce associated image blurring. The desired response for the excitation radiofrequency pulse (Fig.…”

“…However, with improvements in gas-polarization hardware (12), liter quantities of hyperpolarized Xe129 can be obtained with sufficient polarization to make direct dissolved-phase imaging in humans feasible during a single breath-hold period. Recently, Cleveland et al (13) produced breath-hold images of the dissolved phase in humans following inhalation of 1 L of Xe129. Nonetheless, because the absolute dissolved-phase signal intensity has no physical meaning, measurement of the dissolved-phase signal alone cannot make the critical distinction between pathological alterations in ventilation (gas delivery to the airspaces) versus those in tissue microstructure or blood flow.…”

Chronic Obstructive Pulmonary Disease: Safety and Tolerability of Hyperpolarized129Xe MR Imaging in Healthy Volunteers and Patients

“…who participated in the technical run-in phase of the trial. The run-in phase was deliberately conducted slowly to permit time to establish optimal technical imaging parameters for 129 Xe ventilation, apparent diffusion coeffi cient ( 22 ), and 129 Xe distribution in the dissolved phase ( 15 ).…”

Abnormalities in Hyperpolarized 129Xe Magnetic Resonance Imaging and Spectroscopy in two Patients with Pulmonary Vascular Disease

“…This technique has demonstrated specific patterns of airway and parenchymal lung disease. 4 In asthma, it was superior to 3 He MRI 5 and revealed ventilation abnormalities before bronchodilation. In IPF, it clearly identifies diffusion limitation along with regional defects and pattern of disease that may be unique compared with other causes of pulmonary fibrosis.…”