¹⁵N Hyperpolarization by Reversible Exchange Using SABRE-SHEATH

Abstract

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. <i>J. Am. Chem. Soc.</i><b>2015</b>, <i>137</i>, 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 (<i>T</i>₁), and reversible oxygen quenching are studied on a test system of ¹⁵N-pyridine in methanol-<i>d</i>₄. 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 <i>T</i>₁ relaxation times suitable for biomedical imaging and spectroscopy.