Parahydrogen is demonstrated to efficiently transfer its nuclear spin hyperpolarization to nitrogen-15 in pyridine and nicotinamide (vitamin B₃ amide) by conducting “signal amplification by reversible exchange” (SABRE) at microtesla fields within a magnetic shield. Following transfer of the sample from the magnetic shield chamber to a conventional NMR spectrometer, the ¹⁵N NMR signals for these molecules are enhanced by ∼30,000- and ∼20,000-fold at 9.4 T, corresponding to ∼10% and ∼7% nuclear spin polarization, respectively. This method, dubbed “SABRE in shield enables alignment transfer to heteronuclei” or “SABRE-SHEATH”, promises to be a simple, cost-effective way to hyperpolarize heteronuclei. It may be particularly useful for in vivo applications because of longer hyperpolarization lifetimes, lack of background signal, and facile chemical-shift discrimination of different species.

NMR signal amplification by reversible exchange (SABRE) is a NMR hyperpolarization technique that enables nuclear spin polarization enhancement of molecules via concurrent chemical exchange of a target substrate and parahydrogen (the source of spin order) on an iridium catalyst. Recently, we demonstrated that conducting SABRE in microtesla fields provided by a magnetic shield enables up to 10% ¹⁵N-polarization (Theis, T.; et al. J. Am. Chem. Soc.2015, 137, 1404). Hyperpolarization on ¹⁵N (and heteronuclei in general) may be advantageous because of the long-lived nature of the hyperpolarization on ¹⁵N relative to the short-lived hyperpolarization of protons conventionally hyperpolarized by SABRE, in addition to wider chemical shift dispersion and absence of background signal. Here we show that these unprecedented polarization levels enable ¹⁵N magnetic resonance imaging. We also present a theoretical model for the hyperpolarization transfer to heteronuclei, and detail key parameters that should be optimized for efficient ¹⁵N-hyperpolarization. The effects of parahydrogen pressure, flow rate, sample temperature, catalyst-to-substrate ratio, relaxation time (T₁), and reversible oxygen quenching are studied on a test system of ¹⁵N-pyridine in methanol-d₄. Moreover, we demonstrate the first proof-of-principle ¹³C-hyperpolarization using this method. This simple hyperpolarization scheme only requires access to parahydrogen and a magnetic shield, and it provides large enough signal gains to enable one of the first ¹⁵N images (2 × 2 mm² resolution). Importantly, this method enables hyperpolarization of molecular sites with NMR T₁ relaxation times suitable for biomedical imaging and spectroscopy.

The exquisite NMR spectral sensitivity and negligible reactivity of hyperpolarized xenon-129 (HP¹²⁹Xe) make it attractive for a number of magnetic resonance applications; moreover, HP¹²⁹Xe embodies an alternative to rare and nonrenewable ³He. However, the ability to reliably and inexpensively produce large quantities of HP¹²⁹Xe with sufficiently high ¹²⁹Xe 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 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” ¹²⁹Xe 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.