Imaging alveolar–capillary gas transfer using hyperpolarized ¹²⁹ Xe MRI

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 Ϸ5 m. 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.diffusing capacity ͉ fibrosis ͉ gas exchange ͉ blood-gas barrier

Bleomycin‐induced lung injury assessed noninvasively and in spontaneously breathing rats by proton MRI

“…Similar results were also obtained in dogs (39). Recently Driehuys et al (40) applied hyperpolarized 129 Xe MRI to a rat model of unilateral BLM lung injury. The 129 Xe signal is detectable in the gas phase (airspace compartment) and once the gas is absorbed into the tissue and red blood cells.…”

Development of an antibody-based, modular biosensor for129Xe NMR molecular imaging of cells at nanomolar concentrations

“…spin hyperpolarization | targeted imaging W hen referring to xenon magnetic resonance imaging (MRI), the best-known application is the use of the isotope 129 Xe for facilitating the direct visualization of the airspaces and function of the lung (1)(2)(3)(4). However, in the past few years, the scope for using 129 Xe for targeted biosensor imaging has notably increased (5).…”

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

“…In particular, xenon's relatively high solubility in biological tissues (2), along with its exquisite sensitivity to its environment that results in an enormous range of chemical shifts upon solution (3), make hyperpolarized Xe129 particularly attractive for exploring certain characteristics of lung function, such as gas exchange and uptake (4,5), not accessible with the use of hyperpolarized He3. Upon inhalation, Xe129 gives rise to multiple MRI spectral peaks in the lung (6)(7)(8)(9), each associated with a physically different compartment.…”