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) 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 D 1 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 (T 1 ∼38 min and ∼5.9 h at ∼1.5 mT and 3 T, respectively)-more than sufficient for a variety of applications.hyperpolarization | laser-polarized xenon | lung imaging | optical pumping O wing to the detection sensitivity provided by their high, nonequilibrium nuclear spin polarization, hyperpolarized (HP) noble gases (e.g., Xe is of particular interest. Moreover, xenon is soluble in blood (6), other tissues (7, 8), and many biologically compatible liquids (9), and its proclivity for interacting with other substances and its wide chemical shift range make HP 129 Xe a sensitive NMR probe of molecular and material surfaces (1,(10)(11)(12) Xe is usually created via spin-exchange optical pumping (SEOP) (23), whereby the unpaired electronic spins of an alkali metal vapor (e.g., Rb) are polarized via optical pumping with circularly polarized light, and the polarization is transferred to noble gas nuclear spins during collisions. It is generally anticipated that high P Xe is achievable only in the low xenon-density regime (18, 24), because (i) higher Xe densities increase the destruction of Rb polarization from nonspin-conserving collisions at a rate that is orders of magnitude worse than those of other gases like N 2 and He (25-27); and (ii) higher total pressures tend to quench the threebody van der Waals contribution to Rb-Xe spin exchange-leaving the less-efficient two-body term (18,23). Most large-scale polarizers, in particular all that are available commercially, operate in this low-Xe density ...

Here we provide a full report on the construction, components, and capabilities of our consortium's "open-source" large-scale (~1 L/hr) 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 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript 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 129 Xe nuclear spin polarization values of ~30-90% have been measured for Xe loadings of ~300-1600 Torr. Typical 129 Xe polarization build-up and T 1 relaxation time constants were ~8.5 min and ~1.9 hr respectively under our SEOP conditions; such ratios, combined with near-unity Rb electron spin polarizations enabled by the high resonant laser power (up to ~200 W), permits such high P Xe 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 6 hr) 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 COPD 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.

Spin-exchange optical pumping (SEOP) has 12 been widely used to produce enhancements in nuclear spin 13 polarisation for hyperpolarised noble gases. However, some 14 key fundamental physical processes underlying SEOP 15 remain poorly understood, particularly in regards to how 16 pump laser energy absorbed during SEOP is thermalised, 17 distributed, and dissipated. This study uses in situ ultra-low 18 frequency Raman spectroscopy to probe rotational temper-19 atures of nitrogen buffer gas during optical pumping under 20 conditions of high resonant laser flux and binary Xe/N 2 gas 21 mixtures. We compare two methods of collecting the Raman 22 scattering signal from the SEOP cell: a conventional 23 orthogonal arrangement combining intrinsic spatial filtering 24 with the utilisation of the internal baffles of the Raman 25 spectrometer, eliminating probe laser light and Rayleigh 26 scattering, versus a new in-line modular design that uses 27 ultra-narrowband notch filters to remove such unwanted 28 contributions. We report a *23-fold improvement in detection sensitivity using the in-line module, which leads to faster data acquisition and more accurate real-time monitoring of energy transport processes during optical pumping. The utility of this approach is demonstrated via measurements of the local internal gas temperature (which can greatly exceed the externally measured temperature) as a function of incident laser power and position within the cell.

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