Hyperpolarized 129Xe MRI of the human lung

By permitting direct visualization of the airspaces of the lung, magnetic resonance imaging (MRI) using hyperpolarized gases provides unique strategies for evaluating pulmonary structure and function. Although the vast majority of research in humans has been performed using hyperpolarized ³He, recent contraction in the supply of ³He and consequent increases in price have turned attention to the alternative agent, hyperpolarized ¹²⁹Xe. Compared to ³He, ¹²⁹Xe yields reduced signal due to its smaller magnetic moment. Nonetheless, taking advantage of advances in gas‐polarization technology, recent studies in humans using techniques for measuring ventilation, diffusion, and partial pressure of oxygen have demonstrated results for hyperpolarized ¹²⁹Xe comparable to those previously demonstrated using hyperpolarized ³He. In addition, xenon has the advantage of readily dissolving in lung tissue and blood following inhalation, which makes hyperpolarized ¹²⁹Xe particularly attractive for exploring certain characteristics of lung function, such as gas exchange and uptake, which cannot be accessed using ³He. Preliminary results from methods for imaging ¹²⁹Xe dissolved in the human lung suggest that these approaches will provide new opportunities for quantifying relationships among gas delivery, exchange, and transport, and thus show substantial potential to broaden our understanding of lung disease. Finally, recent changes in the commercial landscape of the hyperpolarized‐gas field now make it possible for this innovative technology to move beyond the research laboratory. J. Magn. Reson. Imaging 2013;37:313–331. © 2012 Wiley Periodicals, Inc.     

Hyperpolarized 129 Xe MRI of the mouse lung at a low xenon concentration using a continuous flow-type hyperpolarizing system

PURPOSE: To apply a continuous flow-type hyperpolarizing (CF-HP) system to lung imaging and investigate the feasibility of hyperpolarized (129)Xe MRI at a low xenon concentration. MATERIALS AND METHODS: Under two conditions where a 3% or 70% xenon gas mixture was constantly supplied, gas- and dissolved-phase (129)Xe images and diffusion-weighted (129)Xe-gas images were obtained from the mouse lung. Signal-to-noise ratio (SNR) of the (129)Xe images and the apparent diffusion coefficient (ADC) of xenon were compared between the two gas mixtures. RESULTS: The SNR of gas- and dissolved-phase images were 28.9 +/- 5.2 and 12.0 +/- 2.0, respectively, using the 70% xenon gas mixture, while they were 22.9 +/- 4.8 and 6.8 +/- 0.6, using the 3% mixture. The ADC of xenon using the 3% xenon gas mixture was approximately 1.5 times higher than that using the 70% one. These results indicated that the high ADC increases the apparent replenishment rate of gas-phase magnetization, thus resulting in a reduction of the SNR loss induced by diluting xenon with quenching gases. CONCLUSION: The CF-HP system is useful for lung imaging at an extremely low concentration of xenon, which enables one to fully restrain an anesthetic effect of xenon and to reduce consumption of xenon in a measurement.     

Exploring lung function with hyperpolarized (129)Xe nuclear magnetic resonance.

With the use of polarization-transfer pulse sequences and hyperpolarized (129)Xe NMR, gas exchange in the lung can be measured quantitatively. However, harnessing the inherently high sensitivity of this technique as a tool for exploring lung function requires a fundamental understanding of the xenon gas-exchange and diffusion processes in the lung, and how these may differ between healthy and pathological conditions. Toward this goal, we employed NMR spectroscopy and imaging techniques in animal models to investigate the dependence of the relative xenon gas exchange rate on the inflation level of the lung and the tissue density. The spectroscopic results indicate that gas exchange occurs on a time scale of milliseconds, with an average effective diffusion constant of about 3.3 x 10(-6)cm(2)/s in the lung parenchyma. Polarization-transfer imaging pulse sequences, which were optimized based on the spectroscopic results, detected regionally increased gas-exchange rates in the lung, indicative of increased tissue density secondary to gravitational compression. By exploiting the gas-exchange process in the lung to encode physiologic parameters, these methods may be extended to noninvasive regional assessments of lung-tissue density and the alveolar surface-to-volume ratio, and allow lung pathology to be detected at an earlier stage than is currently possible.     

MOXE: A model of gas exchange for hyperpolarized 129Xe magnetic resonance of the lung

We present a model of gas exchange for hyperpolarized ¹²⁹Xe in the lung, which we refer to as the Model of Xenon Exchange. The model consists of two expressions and characterizes uptake of dissolved xenon in the lung at two different resonance frequencies. The two expressions are governed by the following five critical pulmonary parameters that characterize both lung function and structure: the surface‐area‐to‐volume ratio, barrier‐to‐septum ratio (ratio between air–blood barrier thickness and septal thickness), hematocrit, gas‐exchange time constant, and pulmonary capillary transit time. The model is first validated by computer simulation. We show that Model of Xenon Exchange can be used to measure the pulmonary parameters mentioned above under various pathological or physiological conditions and is robust against moderate noise. Model of Xenon Exchange is further used to fit an existing data set of xenon uptake, thereby we demonstrate that the data can be well interpreted with Model of Xenon Exchange and reasonable parameters from the fitting routine. The good results obtained in both simulation and fitting to real data indicate that the model is sensitive to various functional and structural changes of the lung, and that it will allow for screening for a variety of pulmonary diseases by using hyperpolarized ¹²⁹Xe of the lung. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Measurement of 129Xe gas apparent diffusion coefficient anisotropy in an elastase‐instilled rat model of emphysema

Hyperpolarized noble gas (³He and ¹²⁹Xe) apparent diffusion coefficient (ADC) measurements have shown remarkable sensitivity to microstructural (i.e., alveolar) changes in the lung, particularly emphysema. The ADC of hyperpolarized noble gases depends strongly on the diffusion time (Δ), and ³He ADC has been shown to be anisotropic for Δ ranging from a few milliseconds down to a few hundred microseconds. In this study, the anisotropic nature of ¹²⁹Xe diffusion and its dependence on Δ were investigated both numerically, in a budded cylinder model, and in vivo, in an elastase‐instilled rat model of emphysema. Whole lung longitudinal ADC (D_L) and transverse ADC (D_T) were measured for Δ = 6, 50, and 100 ms at 73.5 mT, and correlated with measurements of the mean linear intercept (L_m) obtained from lung histology. A significant increase (P = 0.0021) in D_T was measured for Δ = 6 ms between the sham (0.0021 ± 0.0005 cm²/s) and elastase‐instilled (0.005 ± 0.001 cm²/s) cohorts, and a strong correlation was measured between D_T (Δ = 6 ms) and L_m, with a Pearson's correlation coefficient of 0.90. This study confirms that ¹²⁹Xe D_T increases correlate with alveolar space enlargement due to elastase instillation in rats. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

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

The ability to quantify pulmonary diffusing capacity and perfusion using dynamic hyperpolarized ¹²⁹Xe NMR spectroscopy is demonstrated. A model of alveolar gas exchange was developed, which, in conjunction with ¹²⁹Xe 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 μm, LPS 9.9 ± 0.6 μm, P < 0.001), in capillary diffusion length (control 2.9 ± 0.4 μm, LPS 3.9 ± 1.0 μm, 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. Magn Reson Med 50:1170–1179, 2003. © 2003 Wiley‐Liss, Inc.