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We present a second-generation open-source automated batch-mode 129Xe hyperpolarizer (XeUS GEN-2), designed for clinical-scale hyperpolarized (HP) 129Xe production via spin-exchange optical pumping (SEOP) in the regimes of high Xe density (0.66–2.5 atm partial pressure) and resonant photon flux (~170 W, Δλ = 0.154 nm FWHM), without the need for cryo-collection typically employed by continuous-flow hyperpolarizers. An Arduino micro-controller was used for hyperpolarizer operation. Processing open-source software was employed to program a custom graphical user interface (GUI), capable of remote automation. The Arduino Integrated Development Environment (IDE) was used to design a variety of customized automation sequences such as temperature ramping, NMR signal acquisition, and SEOP cell refilling for increased reliability. A polycarbonate 3D-printed oven equipped with a thermo-electric cooler/heater provides thermal stability for SEOP for both binary (Xe/N2) and ternary (4He-containing) SEOP cell gas mixtures. Quantitative studies of the 129Xe hyperpolarization process demonstrate that near-unity polarization can be achieved in a 0.5 L SEOP cell. For example, %PXe of 93.2 ± 2.9% is achieved at 0.66 atm Xe pressure with polarization build-up rate constant γSEOP = 0.040 ± 0.005 min−1, giving a max dose equivalent ≈ 0.11 L/h 100% hyperpolarized, 100% enriched 129Xe; %PXe of 72.6 ± 1.4% is achieved at 1.75 atm Xe pressure with γSEOP of 0.041 ± 0.001 min−1, yielding a corresponding max dose equivalent of 0.27 L/h. Quality assurance studies on this device have demonstrated the potential to refill SEOP cells hundreds of times without significant losses in performance, with average %PXe = 71.7%, (standard deviation σP = 1.52%) and mean polarization lifetime T1 = 90.5 min, (standard deviation σT = 10.3 min) over the first ~200 gas mixture refills, with sufficient performance maintained across a further ~700 refills. These findings highlight numerous technological developments and have significant translational relevance for efficient production of gaseous HP 129Xe contrast agents for use in clinical imaging and bio-sensing techniques.

The successful transfer of para-hydrogen-induced polarization to 15N spins using heterogeneous catalysts in aqueous solutions was demonstrated. Hydrogenation of a synthesized unsaturated 15N-labeled precursor (neurine) with parahydrogen (p-H2) over Rh/TiO2 heterogeneous catalysts yielded a hyperpolarized structural analogue of choline. As a result, 15N polarization enhancements of over 2 orders of magnitude were achieved for the 15N-labeled ethyltrimethylammonium ion product in deuterated water at elevated temperatures. Enhanced 15N NMR spectra were successfully acquired at 9.4 and 0.05 T. Importantly, long hyperpolarization lifetimes were observed at 9.4 T, with a 15N T1 of ∼6 min for the product molecules, and the T1 of the deuterated form exceeded 8 min. Taken together, these results show that this approach for generating hyperpolarized species with extended lifetimes in aqueous, biologically compatible solutions is promising for various biomedical applications.

We present spin-exchange optical pumping (SEOP) using a third-generation (GEN-3) automated batch-mode clinical-scale 129Xe hyperpolarizer utilizing continuous high-power (∼170 W) pump laser irradia...

The Signal Amplification by Reversible Exchange (SABRE) technique employs exchange with singlet-state parahydrogen to efficiently generate high levels of nuclear spin polarization. Spontaneous SABRE has been shown previously to be efficient in the milli-Tesla and micro-Tesla regimes. We have recently demonstrated that high-field SABRE is also possible, where proton sites of molecules that are able to reversibly coordinate to a metal center can be hyperpolarized directly within high-field magnets, potentially offering the convenience of in situ hyperpolarization-based spectroscopy and imaging without sample shuttling. Here, we show efficient polarization transfer from parahydrogen (para-H2) to the 15N atoms of imidazole-15N2 and nicotinamide-15N achieved via high-field SABRE (HF-SABRE). Spontaneous transfer of spin order from the para-H2 protons to 15N atoms at the high magnetic field of an MRI scanner allows one not only to record enhanced 15N NMR spectra of in situ hyperpolarized biomolecules, but also to perform imaging using conventional MRI sequences. 2D 15N MRI of high-field SABRE-hyperpolarized imidazole with spatial resolution of 0.3×0.3 mm2 at 9.4 T magnetic field and a high signal-to-noise ratio (SNR) of ~99 was demonstrated. We show that 1H MRI of in situ HF-SABRE hyperpolarized biomolecules (e.g. imidazole-15N2) is also feasible. Taken together, these results show that heteronuclear (15N) and 1H spectroscopic detection and imaging of high-field-SABRE-hyperpolarized molecules are promising tools for a number of emerging applications.