Structural and functional pulmonary imaging using hyperpolzarized xenon-129

We describe applications of hyperpolarized 129 Xe to pulmonary imaging. Unique characteristics of this gas such as its polarizability and diffusibility in tissue allow probing important properties of the lungs. Three methods that study structure and function of the lungs, Chemical Shift Saturation Recovery (CSSR), Xenon polarization Transfer Contrast (XTC) and Dixon, and their application to human studies for the first time are the focus of this work. CSSR measures the global fractional gas transport, F(t) in the lungs. Using this method the dynamics of gas exchange were studied. A model describing this process was derived and used to interpret data obtained with CSSR. Studies were conducted on a number of healthy subjects as well as patients with mild to moderate Interstitial Lung Disease. CSSR was able to distinguish the healthy group from the rest by the measured septal thickness. XTC is an imaging technique, in which the gas-phase signal is attenuated by inverting the spins of 129 Xe particles dissolved into the parenchyma. Using this technique 2D maps of the fractional gas transport, F(t) occurring in the lungs were obtained. Studies were performed at two lung volumes, and showed the at lower volumes, fractional gas transport and therefore the alveolar surface per unit volume is higher for all subjects. Difference in the fractional gas transport from apex to base was detected in the supine position with greater values at the bases. Comparison between health non-smokers and asymptomatic smokers was made. We observed a higher mean value of F(t) and physiological heterogeneity in smokers compared to non-smokers. Preliminary results suggest that XTC is more sensitive to the early changes in the lungs compared to the gold standard tests, such as DLCO and FEV 1. Dixon is another imaging modality, which can be used to measure local S/V. It provides a direct simultaneous measurement of the dissolved and gaseous phases of inspired Xe. It yields a 2D map of F(t). Higher values of F(t) accompanied by a larger spread was observed at lower lung volumes

Near-unity nuclear polarization with an open-source 129Xe hyperpolarizer for NMR and MRI

The exquisite NMR spectral sensitivity and negligible reactivity of hyperpolarized xenon-129 (HP129Xe) make it attractive for a number of magnetic resonance applications; moreover, HP129Xe embodies an alternative to rare and nonrenewable 3He. However, the ability to reliably and inexpensively produce large quantities of HP129Xe with sufficiently high 129Xe nuclear spin polarization (PXe) remains a significant challenge—particularly at high Xe densities. We present results from our “open-source” large-scale (∼1 L/h) 129Xe polarizer for clinical, preclinical, and materials NMR and MRI research. Automated and composed mostly of off-the-shelf components, this “hyperpolarizer” is designed to be readily implementable in other laboratories. The device runs with high resonant photon flux (up to 200 W at the Rb D1 line) in the xenon-rich regime (up to 1,800 torr Xe in 500 cc) in either single-batch or stopped-flow mode, negating in part the usual requirement of Xe cryocollection. Excellent agreement is observed among four independent methods used to measure spin polarization. In-cell PXe values of ∼90%, ∼57%, ∼50%, and ∼30% have been measured for Xe loadings of ∼300, ∼500, ∼760, and ∼1,570 torr, respectively. PXe values of ∼41% and ∼28% (with ∼760 and ∼1,545 torr Xe loadings) have been measured after transfer to Tedlar bags and transport to a clinical 3 T scanner for MR imaging, including demonstration of lung MRI with a healthy human subject. Long “in-bag” 129Xe polarization decay times have been measured (T1 ∼38 min and ∼5.9 h at ∼1.5 mT and 3 T, respectively)—more than sufficient for a variety of applications

XeNA: an automated ‘open-source’ 129Xe hyperpolarizer for clinical use

Here we provide a full report on the construction, components, and capabilities of our consortium’s “open-source” large-scale (~ 1 L/h) 129Xe hyperpolarizer for clinical, pre-clinical, and materials NMR/MRI (Nikolaou et al., Proc. Natl. Acad. Sci. USA, 110, 14150 (2013)). The ‘hyperpolarizer’ is automated and built mostly of off-the-shelf components; moreover, it is designed to be cost-effective and installed in both research laboratories and clinical settings with materials costing less than $125,000. The device runs in the xenon-rich regime (up to 1800 Torr Xe in 0.5 L) in either stopped-flow or single-batch mode—making cryo-collection of the hyperpolarized gas unnecessary for many applications. In-cell 129Xe nuclear spin polarization values of ~ 30%–90% have been measured for Xe loadings of ~ 300–1600 Torr. Typical 129Xe polarization build-up and T1 relaxation time constants were ~ 8.5 min and ~ 1.9 h respectively under our spin-exchange optical pumping conditions; such ratios, combined with near-unity Rb electron spin polarizations enabled by the high resonant laser power (up to ~ 200 W), permit such high PXe values to be achieved despite the high in-cell Xe densities. Importantly, most of the polarization is maintained during efficient HP gas transfer to other containers, and ultra-long 129Xe relaxation times (up to nearly 6 h) were observed in Tedlar bags following transport to a clinical 3 T scanner for MR spectroscopy and imaging as a prelude to in vivo experiments. The device has received FDA IND approval for a clinical study of chronic obstructive pulmonary disease subjects. The primary focus of this paper is on the technical/engineering development of the polarizer, with the explicit goals of facilitating the adaptation of design features and operative modes into other laboratories, and of spurring the further advancement of HP-gas MR applications in biomedicine

Single-breath xenon polarization transfer contrast (SB-XTC):Implementation and initial results in healthy humans

PURPOSE: To implement and characterize a single-breath xenon transfer contrast (SB-XTC) method to assess the fractional diffusive gas transport F in the lung: to study the dependence of F and its uniformity as a function of lung volume; to estimate local alveolar surface area per unit gas volume S(A)/V(Gas) from multiple diffusion time measurements of F; to evaluate the reproducibility of the measurements and the necessity of B(1) correction in cases of centric and sequential encoding. MATERIALS AND METHODS: In SB-XTC three or four gradient echo images separated by inversion/saturation pulses were collected during a breath-hold in eight healthy volunteers, allowing the mapping of F (thus S(A)/V(Gas)) and correction for other contributions such as T(1) relaxation, RF depletion and B(1) inhomogeneity from inherently registered data. RESULTS: Regional values of F and its distribution were obtained; both the mean value and heterogeneity of F increased with the decrease of lung volume. Higher values of F in the bases of the lungs in supine position were observed at lower volumes in all volunteers. Local S(A)/V(Gas) (with a mean ± standard deviation of [Formula: see text]) was estimated in vivo near functional residual capacity. Calibration of SB-XTC on phantoms highlighted the necessity for B(1) corrections when k-space is traversed sequentially; with centric ordering B(1) distribution correction is dispensable. CONCLUSION: SB-XTC technique is implemented and validated for in vivo measurements of local S(A)/V(Gas)