13C and 15N NMR Detection of Metabolites via Relayed Hyperpolarization at 1 T and 1.4 T

Nuclear-spin hyperpolarization allows various magnetic-resonance applications in chemistry and medicine that are unattainable by standard methods. For such applications, parahydrogen-based hyperpolarization approaches are particularly attractive because of their technical simplicity, low cost, and ability to quickly (in seconds) produce large volumes of hyperpolarized material. Although many parahydrogen-based techniques have emerged, some of them remain unexplored due to the lack of careful optimization studies. In this work, we investigate and optimize a novel parahydrogen-induced polarization (PHIP) technique that relies on proton exchange referred to below as PHIP-relay. An INEPT (insensitive nuclei enhanced by polarization transfer) sequence is employed to transfer polarization from hyperpolarized protons to heteronuclei (15N and 13C) and nuclear signals are detected using benchtop NMR spectrometers (1 T and 1.4 T, respectively). We demonstrate the applicability of the PHIP-relay technique for hyperpolarization of a wide range of biochemicals by examining such key metabolites as urea, ammonium, glucose, amino acid glycine, and a drug precursor benzamide. By optimizing chemical and NMR parameters of the PHIP-relay, we achieve a 17,100-fold enhancement of 15N signal of [13C, 15N2]-urea compared to the thermal signal measured at 1 T. We also show that repeated measurements with shorter exposure to parahydrogen provide a higher effective signal-to-noise ratio compared to longer parahydrogen bubbling.