Abstract
NMR hyperpolarization techniques have the potential to revolutionize the field of NMR spectroscopy and molecular MRI because they can transiently enhance nuclear spin polarization by 4-8 orders of magnitude, with corresponding gains in NMR signal-to-noise ratio (SNR). The SABRE-SHEATH (Signal Amplification By Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei) technique, first demonstrated in 2015, allows for direct, efficient (>20% nuclear spin polarization), and fast (in under one minute) hyperpolarization of N-15 sites. Several classes of biologically relevant N-15 hyperpolarized contrast agents have been efficiently hyperpolarized to date including pH sensors, which can be potentially useful for non-invasive pH imaging of cancer and other diseases with altered metabolism. Here, we report the optimized N-15 enrichment of imidazole-N-15(2) - a promising invivo pH sensor with pKa similar to 7.0. A hyperpolarized 0.1M aqueous solution (epsilon(15N) similar to 146,000 fold, P-15N similar to 0.24%) was used to record (NNMR)-N-15 spectra at 0.05 T, demonstrating the feasibility of high-resolution (full width at half maximum similar to 1Hz corresponding to 5ppm at 0.05 T) NMR spectroscopy near its pKa (7.0) at ultra-low magnetic field. Given that proton-binding events modulate the chemical shift by similar to 30ppm for this pH-sensing probe, our results demonstrate the feasibility of ultra-low-field pH sensing near its pKa (7.0) with SNR approaching that of high-field (9.4 T) MR.