We present spin-exchange optical pumping (SEOP) using a third-generation (GEN-3) automated batch-mode clinicalscale 129 Xe hyperpolarizer utilizing continuous high-power (∼170 W) pump laser irradiation and a novel aluminum jacket design for rapid temperature ramping of xenon-rich gas mixtures (up to 2 atm partial pressure). The aluminum jacket design is capable of heating SEOP cells from ambient temperature (typically 25°C) to 70°C (temperature of the SEOP process) in 4 min, and perform cooling of the cell to the temperature at which the hyperpolarized gas mixture can be released from the hyperpolarizer (with negligible amounts of Rb metal leaving the cell) in approximately 4 min, substantially faster (by a factor of 6) than previous hyperpolarizer designs relying on air heat exchange. These reductions in temperature cycling time will likely be highly advantageous for the overall increase of production rates of batch-mode (i.e., stopped-flow) 129 Xe hyperpolarizers, which is particularly beneficial for clinical applications. The additional advantage of the presented design is significantly improved thermal management of the SEOP cell. Accompanying the heating jacket design and performance, we also evaluate the repeatability of SEOP experiments conducted using this new architecture, and present typically achievable hyperpolarization levels exceeding 40% at exponential build-up rates on the order of 0.1 min −1 .

Prof. Eduard Y. Chekmenev received his PhD in Physical Chemistry (supervisor Prof. Richard J. Wittebort) in 2003 at the University of Louisville, KY (USA). He conducted postdoctoral research at the National High Magnetic Field Laboratory in Tallahassee, FL (with Prof. Timothy Cross), Caltech (Prof. Daniel P. Weitekamp) and HMRI in Pasadena, CA (USA) (with Dr.B rian D. Ross). In 2009, Dr.C hekmenev started his hyperpolarization program at Vanderbilt University (Nashville, TN) and he was tenured in 2015. In 2018, he moved to Wayne State University (Detroit, MI) to continue his research on MR hyperpolarization.Figure 1. Thermal equilibrium polarizationp roduces asmall excess of spins in one state. When the sample undergoes hyperpolarization, alarge excess of spins exists in one state producingaconsiderably stronger signal since more spins contribute.

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We present on the utility of in situ nuclear magnetic resonance (NMR) and near-infrared (NIR) spectroscopic techniques for automated advanced analysis of the 129Xe hyperpolarization process during spin-exchange optical pumping (SEOP). The developed software protocol, written in the MATLAB programming language, facilitates detailed characterization of hyperpolarized contrast agent production efficiency based on determination of key performance indicators, including the maximum achievable 129Xe polarization, steady-state Rb–129Xe spin-exchange and 129Xe polarization build-up rates, 129Xe spin-relaxation rates, and estimates of steady-state Rb electron polarization. Mapping the dynamics of 129Xe polarization and relaxation as a function of SEOP temperature enables systematic optimization of the batch-mode SEOP process. The automated analysis of a typical experimental data set, encompassing ∼300 raw NMR and NIR spectra combined across six different SEOP temperatures, can be performed in under 5 min on a laptop computer. The protocol is designed to be robust in operation on any batch-mode SEOP hyperpolarizer device. In particular, we demonstrate the implementation of a combination of low-cost NIR and low-frequency NMR spectrometers (∼$1,100 and ∼$300 respectively, ca. 2020) for use in the described protocols. The demonstrated methodology will aid in the characterization of NMR hyperpolarization hardware in the context of SEOP and other hyperpolarization techniques for more robust and less expensive clinical production of HP 129Xe and other contrast agents.

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Hyperpolarization is a technique that can increase nuclear spin polarization with the corresponding gains in nuclear magnetic resonance (NMR) signals by 4–8 orders of magnitude. When this process is applied to biologically relevant samples, the hyperpolarized molecules can be used as exogenous magnetic resonance imaging (MRI) contrast agents. A technique called spin‐exchange optical pumping (SEOP) can be applied to hyperpolarize noble gases such as 129Xe. Techniques based on hyperpolarized 129Xe are poised to revolutionize clinical lung imaging, offering a non‐ionizing, high‐contrast alternative to computed tomography (CT) imaging and conventional proton MRI. Moreover, CT and conventional proton MRI report on lung tissue structure but provide little functional information. On the other hand, when a subject breathes hyperpolarized 129Xe gas, functional lung images reporting on lung ventilation, perfusion and diffusion with 3D readout can be obtained in seconds. In this Review, the physics of SEOP is discussed and the different production modalities are explained in the context of their clinical application. We also briefly compare SEOP to other hyperpolarization methods and conclude this paper with the outlook for biomedical applications of hyperpolarized 129Xe to lung imaging and beyond.