Imaging of Biomolecular NMR Signals Amplified by Reversible Exchange with Parahydrogen Inside an MRI Scanner

Abstract

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 <i>in situ</i> hyperpolarization-based spectroscopy and imaging without sample shuttling. Here, we show efficient polarization transfer from parahydrogen (<i>para</i>-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 <i>para</i>-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 <i>in situ</i> 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 <i>in situ</i> HF-SABRE hyperpolarized biomolecules (<i>e.g</i>. 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.