(15)N Hyperpolarization by Reversible Exchange Using SABRE-SHEATH

[Image: see text] 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% (15)N-polarization (Theis, T.; et al. J. Am. Chem. Soc.2015, 137, 1404). Hyperpolarization on (15)N (and heteronuclei in general) may be advantageous because of the long-lived nature of the hyperpolarization on (15)N 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 (15)N 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 (15)N-hyperpolarization. The effects of parahydrogen pressure, flow rate, sample temperature, catalyst-to-substrate ratio, relaxation time (T(1)), and reversible oxygen quenching are studied on a test system of (15)N-pyridine in methanol-d(4). Moreover, we demonstrate the first proof-of-principle (13)C-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 (15)N images (2 × 2 mm(2) resolution). Importantly, this method enables hyperpolarization of molecular sites with NMR T(1) relaxation times suitable for biomedical imaging and spectroscopy.