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.     

In vivo MRI using real-time production of hyperpolarized 129Xe

MR imaging of hyperpolarized (HP) nuclei is challenging because they are typically delivered in a single dose of nonrenewable magnetization, from which the entire image must be derived. This problem can be overcome with HP (129)Xe, which can be produced sufficiently rapidly to deliver in dilute form (1%) continuously and on-demand. We demonstrate a real-time in vivo delivery of HP (129)Xe mixture to rats, a capability we now routinely use for setting frequency, transmitter gain, shimming, testing pulse sequences, scout imaging, and spectroscopy. Compared to images acquired using conventional fully concentrated (129)Xe, real-time (129)Xe images have 26-fold less signal, but clearly depict ventilation abnormalities. Real-time (129)Xe MRI could be useful for time-course studies involving acute injury or response to treatment. Ultimately, real-time (129)Xe MRI could be done with more highly concentrated (129)Xe, which could increase the signal-to-noise ratio by 100 relative to these results to enable a new class of gas imaging applications.     

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.     

MR imaging and spectroscopy using hyperpolarized 129Xe gas: Preliminary human results

Using a new method of xenon laser-polarization that permits the generation of liter quantities of hyperpolarized ¹²⁹Xe gas, the first ¹²⁹Xe imaging results from the human chest and the first ¹²⁹Xe spectroscopy results from the human chest and head have been obtained. With polarization levels of approximately 2%, cross-sectional images of the lung gas-spaces with a voxel volume of 0.9 cm³ (signal-to-noise ratio (SNR), 28) were acquired and three dissolved-phase resonances in spectra from the chest were detected. In spectra from the head, one prominent dissolved-phase resonance, presumably from brain parenchyma, was detected. With anticipated improvements in the ¹²⁹Xe polarization system, pulse sequences, RF coils, and breathing maneuvers, these results suggest the possibility for ¹²⁹Xe gas-phase imaging of the lungs with a resolution approaching that of current conventional thoracic proton imaging. Moreover, the results suggest the feasibility of dissolved-phase imaging of both the chest and brain with a resolution similar to that obtained with the gas-phase images.     

Diffusion‐weighted hyperpolarized 129Xe MRI in healthy volunteers and subjects with chronic obstructive pulmonary disease

Given its greater availability and lower cost, ¹²⁹Xe apparent diffusion coefficient (ADC) MRI offers an alternative to ³He ADC MRI. To demonstrate the feasibility of hyperpolarized ¹²⁹Xe ADC MRI, we present results from healthy volunteers (HV), chronic obstructive pulmonary disease (COPD) subjects, and age‐matched healthy controls (AMC). The mean parenchymal ADC was 0.036 ± 0.003 cm² sec^?1 for HV, 0.043 ± 0.006 cm² sec^?1 for AMC, and 0.056 ± 0.008 cm² sec^?1 for COPD subjects with emphysema. In healthy individuals, but not the COPD group, ADC decreased significantly in the anterior–posterior direction by ～22% (P = 0.006, AMC; 0.0059, HV), likely because of gravity‐induced tissue compression. The COPD group exhibited a significantly larger superior–inferior ADC reduction (～28%) than the healthy groups (～24%) (P = 0.00018, HV; P = 3.45 × 10^?5, AMC), consistent with smoking‐related tissue destruction in the superior lung. Superior–inferior gradients in healthy subjects may result from regional differences in xenon concentration. ADC was significantly correlated with pulmonary function tests (forced expiratory volume in 1 sec, r = ?0.77, P = 0.0002; forced expiratory volume in 1 sec/forced vital capacity, r = ?0.77, P = 0.0002; diffusing capacity of carbon monoxide in the lung/alveolar volume (V_A), r = ?0.77, P = 0.0002). In healthy groups, ADC increased with age by 0.0002 cm² sec^?1 year^?1 (r = 0.56, P = 0.02). This study shows that ¹²⁹Xe ADC MRI is clinically feasible, sufficiently sensitive to distinguish HV from subjects with emphysema, and detects age‐ and posture‐dependent changes. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Measurement of xenon diffusing capacity in the rat lung by hyperpolarized 129Xe MRI and dynamic spectroscopy in a single breath-hold.

We used the dual capability of hyperpolarized 129Xe for spectroscopy and imaging to develop new measures of xenon diffusing capacity in the rat lung that (analogously to the diffusing capacity of carbon monoxide or DLCO) are calculated as a product of total lung volume and gas transfer rate constants divided by the pressure gradient. Under conditions of known constant pressure breath-hold, the volume is measured by hyperpolarized 129Xe MRI, and the transfer rate is measured by dynamic spectroscopy. The new quantities (xenon diffusing capacity in lung parenchyma (DLXeLP)), xenon diffusing capacity in RBCs (DLXeRBC), and total lung xenon diffusing capacity (DLXe)) were measured in six normal rats and six rats with lung inflammation induced by instillation of fungal spores of Stachybotrys chartarum. DLXeLP, DLXeRBC, and DLXe were 56 +/- 10 ml/min/mmHg, 64 +/- 35 ml/min/mmHg, and 29 +/- 9 ml/min/mmHg, respectively, for normal rats, and 27 +/- 9 ml/min/mmHg, 42 +/- 27 ml/min/mmHg, and 16 +/- 7 ml/min/mmHg, respectively, for diseased rats. Lung volumes and gas transfer times for LP (TtrLP) were 16 +/- 2 ml and 22 +/- 3 ms, respectively, for normal rats and 12 +/- 2 ml and 35 +/- 8 ms, respectively, for diseased rats. Xenon diffusing capacities may be useful for measuring changes in gas exchange associated with inflammation and other lung diseases.