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.

We present a systematic, multiparameter study of Rb/129Xe 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 129Xe polarization as a function of SEOP-cell operating temperature, photon flux, and xenon partial pressure to maximize 129Xe 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 129Xe 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 129Xe production efficiency.

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Spin-exchange optical pumping (SEOP) can enhance the NMR sensitivity of noble gases by up to five orders of magnitude at Tesla-strength magnetic fields. SEOP-generated hyperpolarised (HP) 129 Xe is a promising contrast agent for lung imaging but an ongoing barrier to widespread clinical usage has been eco-

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