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