Characterization of diffusing capacity and perfusion of the rat lung in a lipopolysaccaride disease model using hyperpolarized ¹²⁹Xe

Abstract

The ability to quantify pulmonary diffusing capacity and perfusion using dynamic hyperpolarized 129 Xe NMR spectroscopy is demonstrated. A model of alveolar gas exchange was developed, which, in conjunction with 129 Xe NMR, enables quantification of average alveolar wall thickness, pulmonary perfusion, capillary diffusion length, and mean transit time. The technique was employed to compare a group of naïve rats (n ‫؍‬ 10) with a group of rats with acute inflammatory lung injury (n ‫؍‬ 10), caused by instillation of lipopolysaccaride (LPS). The measured structural and perfusion-related parameters were in agreement with reported values from studies using non-NMR methods. Significant differences between the groups were found in total diffusion length (control 8.5 ؎ 0.5 m, LPS 9.9 ؎ 0.6 m, P < 0.001), in capillary diffusion length (control 2.9 ؎ 0.4 m, LPS 3.9 ؎ 1.0 m, P < 0.05), and in pulmonary hematocrit (control 0.55 ؎ 0.06, LPS 0.43 ؎ 0.08, P < 0.01), whereas no differences were observed in alveolar wall thickness, pulmonary perfusion, and mean transit time. These results demonstrate the ability of the method to distinguish two main aspects of lung function, namely, diffusing capacity and pulmonary perfusion. Key words: hyperpolarized gas NMR; xenon-129; lung function; diffusing capacity; pulmonary perfusion Gas transfer from ambient air to the blood involves different transport mechanisms. Alveolar ventilation is accomplished by convective transport. Gas transfer within the alveolus and from the alveolus into the blood stream occurs by diffusion along concentration gradients. The blood is then transported from the lungs to peripheral tissues by the pulmonary circulation. These transport processes are affected by a number of lung diseases. Convective transport in the airways is impaired in obstructive lung diseases (1). Diffusion impairment occurs in interstitial lung diseases as well as in pulmonary edema (2). The pulmonary vasculature is affected by both primary lung disease and by left heart failure, causing abnormalities in blood flow (3).The most common method of assessment of diffusion in the alveolar-capillary unit is measurement of the diffusing capacity for carbon monoxide, DL CO (4). The diffusing capacity is defined as the total rate of gas passage across the alveolar-capillary membrane per unit of partial pressure difference of the gas. The tracer gas carbon monoxide diffuses across the alveolar-capillary barrier and is tightly bound to hemoglobin in the erythrocytes. In addition to factors determining diffusion, e.g., the available surface area and the diffusion path length, DL CO therefore depends also on the availability of binding sites, i.e., on hemoglobin concentration and on perfusion. DL CO provides information about diffusion properties of the lung as a whole, but no regional information about function is obtained. By measurement at different partial pressures for oxygen, DL CO can be subdivided into the membrane conductance and a term reflecting the availability of binding sites. This is...

Imaging alveolar–capillary gas transfer using hyperpolarized 129 Xe MRI

“…As 129 Xe leaves the barrier and reaches the RBCs, its frequency shifts to 211 ppm from the gas frequency (11); we refer to this as the ''RBC'' resonance. Collectively, we refer to the 197-and 211-ppm signals as the ''dissolved phase,'' consistent with published literature (8,12). Fig.…”

“…Because the predicted RBC replenishment delay is a spatially localized phenomenon in injured lungs, the effect has not been observed in the whole-lung 129 Xe dynamic spectroscopy studies performed to date (8,13). Adjacent regions of healthy lung would always contribute rapid RBC signal replenishment to the spectrum, thus obscuring RBC delay.…”

“…In healthy alveoli, the harmonic mean thickness [as defined by Weibel (7)] of the blood-gas barrier is 0.77 m and oxygen traverses this space in less than 1 ms, saturating the red blood cells (RBCs) in tens of milliseconds. However, in regions where the barrier is thickened, oxygen cannot diffuse across it fast enough to saturate the RBCs before they exit the gas exchange region [750 ms in humans (5), 300 ms in rats (8)]. A method to noninvasively and directly image alveolar-capillary gas transfer could be very useful to both diagnose and study interstitial lung diseases.…”

Functional lung imaging using hyperpolarized gas MRI

“…However, recent advances in parallel MRI and improvements in Xe-129 polarization (45) have encouraged studies using regional imaging techniques (Fig. 6) and whole lung spectroscopy in animal models of disease (46,97,98).…”

Small Animal Imaging with Hyperpolarized 129Xe Magnetic Resonance

“…It has been reported that several physiological quantities related to these processes were globally evaluated from measurements of alveolar gas uptake dynamics using CSSR in animals 30,[42][43][44][45] and humans. 39,46,47 Whole-lung spectroscopy, however, limits the assessments to be accepted as global measures without any information about the spatial distribution in the lung.…”