In vivo MR imaging and spectroscopy using hyperpolarized 129Xe

Hyperpolarized ¹²⁹Xe has been used to obtain gas phase images of mouse lung in vivo, showing distinct ventilation variation as a function of the breathing cycle. Spectra of ¹²⁹Xe in the thorax show complex structure in both the gas phase (−4 to 3 ppm) and tissue-dissolved (190-205 ppm) regions. The alveolar gas peak shows correlated intensity and frequency oscillations, both attributable to changes in lung volume during breathing. The two major dissolved peaks near 195-200 ppm are attributed to lung parenchyma and to blood; they reach maximum intensity in 5-10 s and decay with an apparent T₁ of 30 s. Another peak at 190 ppm takes 20-30 s to reach maximum; this must represent other well-vascularized tissue (e.g., heart and other muscles) in the thorax. The maximum integrated area of the tissue components reaches 30–80% of the maximum alveolar gas area, indicating that imaging at tissue frequencies can be achieved.     

Direct imaging of hyperpolarized 129Xe alveolar gas uptake in a mouse model of emphysema

MRI of hyperpolarized ¹²⁹Xe dissolved in pulmonary tissues, and blood has the potential to offer a new tool for regional evaluation of pulmonary gas exchange and perfusion; however, the extremely short T and low magnetization density make it difficult to acquire the image. In this study, an ultrashort echo‐time sequence was introduced, and its feasibility to quantitatively assess emphysema‐like pulmonary tissue destruction by a combination of dissolved‐ and gas‐phase ¹²⁹Xe lung MRI was investigated. The ultrashort echo‐time has made it possible to acquire dissolved ¹²⁹Xe images with reasonably high spatial resolution of 0.625 × 0.625 mm² and to obtain T of 0.67 ± 0.30 ms in a spontaneously breathing mouse at 9.4 T. The regional dynamic alveolar gas uptake as well as subsequent transport by pulmonary blood flow was also visualized. The ratio of ¹²⁹Xe magnetization that diffused into the septa relative to the gas‐phase magnetization F was regionally evaluated. The mean F value of elastase‐treated mice was 2.28 ± 0.46%, which was significantly reduced from that of control mice 3.41 ± 0.48% (P = 0.0052). This reflects the reduced uptake efficiency due to alveolar tissue destruction and is correlated with the histologically derived alveolar surface‐to‐volume ratio. Magn Reson Med, 2013. © 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.     

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.     

Large production system for hyperpolarized 129Xe for human lung imaging studies

RATIONALE AND OBJECTIVES: Hyperpolarized gases such as (129)Xe and (3)He have high potential as imaging agents for functional lung magnetic resonance imaging (MRI). We present new technology offering (129)Xe production rates with order-of-magnitude improvement over existing systems, to liter per hour at 50% polarization. Human lung imaging studies with xenon, initially limited by the modest quantity and quality of hyperpolarized gas available, can now be performed with multiliter quantities several times daily. MATERIALS AND METHODS: The polarizer is a continuous-flow system capable of producing large quantities of highly-polarized (129)Xe through rubidium spin-exchange optical pumping. The low-pressure, high-velocity operating regime takes advantage of the enhancement in the spin exchange rate provided by van der Waals molecules dominating the atomic interactions. The long polarizing column moves the flow of the gas opposite to the laser direction, allowing efficient extraction of the laser light. Separate sections of the system assure full rubidium vapor saturation and removal. RESULTS: The system is capable of producing 64% polarization at 0.3 L/hour Xe production rate. Increasing xenon flow reduces output polarization. Xenon polarization was studied as a function of different system operating parameters. A novel xenon trapping design was demonstrated to allow full recovery of the xenon polarization after the freeze-thaw cycle. Delivery methods of the gas to an offsite MRI facility were demonstrated in both frozen and gas states. CONCLUSIONS: We demonstrated a new concept for producing large quantities of highly polarized xenon. The system is operating in an MRI facility producing liters of hyperpolarized gas for human lung imaging studies.     

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.     

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.     

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.