Quantum coherences as origin and source for further optimization of signal amplification by reversible exchange

Parahydrogen-induced polarization (PHIP) is a quickly developing, cost-efficient hyperpolarization method to enhance MR signals. Here, we study the spin order transfer of parahydrogen (pH2) and a substrate at ultralow-fields (ULF, < 10 mT) using a PHIP variant called signal amplification by reversible exchange (SABRE). PHIP and SABRE already feature high 13C and 15N polarization levels above 20%, however, not for all substrates. We used a magnetic field cycling SQUID-based NMR spectrometer that operates at B0 ≈ 55 μT. SQUID- NMR allows several heteronuclei to be measured simultaneously. Two substrates: 3-19F-pyridine and 15N-acetonitrile were polarized by SABRE in methanol using the [IrIMesCODCl] catalyst system. We observed that high order spin states are generated in the SABRE experiment with a polarization field Bp = 5.2 mT. Using correlation spectroscopy (COSY), we were able to measure multiple quantum coherences (MQC) and differentiate them using a 4-step phase cycle technique. Homonuclear (TH or TF) and heteronuclear 1H-19F (THF) coherences of 19F-pyridine from -3 to +3 were detectable experimentally. Alternating magnetic fields between Blow ~ 1 μT and B0 (alt-SABRE-SHEATH) make use of the strong coupling at Blow and the fast coherent evolution at B0. The spin order flow between pH2 and 15N of 15N-acetonitrile were measured with the frequency of ν_low≈119.0 Hz at Blow and ν_high≈2541 Hz at B0. The resulting alt-SABRE-SHEATH 15N polarization was up to 30% higher than in the SABRE-SHEATH experiment with an optimal constant hyperpolarization field. Both experiments were reproduced using spin dynamics simulations. The observation of MQCs confirmed the general understanding that at ULF, high order multi-spin states are populated. As a result, polarization is distributed among many spins, resulting in lower polarization for a specific nucleus. Applying new alt-SABRE-SHEATH protocols to other labeled metabolites (e.g. nicotinamide) and drugs (e.g. metronidazole) might further improve this technique towards in vivo applications