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

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 in situ hyper-polarization-based spectroscopy and imaging without sample shuttling. Here, we show efficient polarization transfer from parahydrogen (para-H-2) to the N-15 atoms of imidazole-N-15(2) and nicotinamide-N-15 achieved via high-field SABRE (HF-SABRE). Spontaneous transfer of spin order from the para-H-2 protons to N-15 atoms at the high magnetic field of an MRI scanner allows one not only to record enhanced N-15 NMR spectra of in situ hyperpolarized biomolecules but also to perform imaging using conventional MRI sequences. 2D N-15 MRI of high-field SABRE-hyperpolarized imidazole with spatial resolution of 0.3 x 0.3 mm(2) at 9.4 T magnetic field and a high signal-to-noise ratio (SNR) of similar to 99 was demonstrated. We show that H-1 MRI of in situ HF-SABRE hyperpolarized biomolecules (e.g., imidazole-N-15(2)) is also feasible. Taken together, these results show that heteronuclear (N-15) and H-1 spectroscopic detection and imaging of high-field-SABRE-hyperpolarized molecules are promising tools for a number of emerging applications.