Multidimensional mapping of spin-exchange optical pumping in clinical-scale batch-mode 129Xe hyperpolarizers.

We present a systematic, multiparameter study of Rb/(129)Xe spin-exchange optical pumping (SEOP) in the regimes of high xenon pressure and photon flux using a 3D-printed, clinical-scale stopped-flow hyperpolarizer. In situ NMR detection was used to study the dynamics of (129)Xe polarization as a function of SEOP-cell operating temperature, photon flux, and xenon partial pressure to maximize (129)Xe polarization (PXe). PXe values of 95 ± 9%, 73 ± 4%, 60 ± 2%, 41 ± 1%, and 31 ± 1% at 275, 515, 1000, 1500, and 2000 Torr Xe partial pressure were achieved. These PXe polarization values were separately validated by ejecting the hyperpolarized (129)Xe gas and performing low-field MRI at 47.5 mT. It is shown that PXe in this high-pressure regime can be increased beyond already record levels with higher photon flux and better SEOP thermal management, as well as optimization of the polarization dynamics, pointing the way to further improvements in hyperpolarized (129)Xe production efficiency.

XeNA: an automated 'open-source' (129)Xe hyperpolarizer for clinical use.

Here we provide a full report on the construction, components, and capabilities of our consortium's "open-source" large-scale (~1L/h) (129)Xe 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 1800Torr Xe in 0.5L) in either stopped-flow or single-batch mode-making cryo-collection of the hyperpolarized gas unnecessary for many applications. In-cell (129)Xe nuclear spin polarization values of ~30%-90% have been measured for Xe loadings of ~300-1600Torr. Typical (129)Xe polarization build-up and T1 relaxation time constants were ~8.5min and ~1.9h 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 ~200W), 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 (129)Xe relaxation times (up to nearly 6h) were observed in Tedlar bags following transport to a clinical 3T 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.

A 3D-printed high power nuclear spin polarizer.

Three-dimensional printing with high-temperature plastic is used to enable spin exchange optical pumping (SEOP) and hyperpolarization of xenon-129 gas. The use of 3D printed structures increases the simplicity of integration of the following key components with a variable temperature SEOP probe: (i) in situ NMR circuit operating at 84 kHz (Larmor frequencies of (129)Xe and (1)H nuclear spins), (ii) <0.3 nm narrowed 200 W laser source, (iii) in situ high-resolution near-IR spectroscopy, (iv) thermoelectric temperature control, (v) retroreflection optics, and (vi) optomechanical alignment system. The rapid prototyping endowed by 3D printing dramatically reduces production time and expenses while allowing reproducibility and integration of "off-the-shelf" components and enables the concept of printing on demand. The utility of this SEOP setup is demonstrated here to obtain near-unity (129)Xe polarization values in a 0.5 L optical pumping cell, including ∼74 ± 7% at 1000 Torr xenon partial pressure, a record value at such high Xe density. Values for the (129)Xe polarization exponential build-up rate [(3.63 ± 0.15) × 10(-2) min(-1)] and in-cell (129)Xe spin-lattice relaxation time (T1 = 2.19 ± 0.06 h) for 1000 Torr Xe were in excellent agreement with the ratio of the gas-phase polarizations for (129)Xe and Rb (PRb ∼ 96%). Hyperpolarization-enhanced (129)Xe gas imaging was demonstrated with a spherical phantom following automated gas transfer from the polarizer. Taken together, these results support the development of a wide range of chemical, biochemical, material science, and biomedical applications.

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 (HP(129)Xe) make it attractive for a number of magnetic resonance applications; moreover, HP(129)Xe embodies an alternative to rare and nonrenewable (3)He. However, the ability to reliably and inexpensively produce large quantities of HP(129)Xe with sufficiently high (129)Xe nuclear spin polarization (P(Xe)) remains a significant challenge--particularly at high Xe densities. We present results from our "open-source" large-scale (∼1 L/h) (129)Xe 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 P(Xe) values of ∼90%, ∼57%, ∼50%, and ∼30% have been measured for Xe loadings of ∼300, ∼500, ∼760, and ∼1,570 torr, respectively. P(Xe) 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" (129)Xe 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.