Efficient Transformation of Parahydrogen Spin Order into Heteronuclear Magnetization

Spin order obtained in the strong coupling regime of protons from parahydrogen-induced hyperpolarization (PHIP) is initially captured as an ensemble of singlet states. For biomedical applications of PHIP, locking this spin order on long-lived heteronuclear storage nuclei increases spectral dispersion, reduces background interference from water protons, and eliminates the need to synchronize subsequent detection pulse sequences to accrued singlet-state evolution. A variety of traditional sequences such as INEPT or HMQC are available to interconvert heteronuclear single quantum coherences at high field, but new approaches are required for converting singlet states into heteronuclear single quantum coherences at low field in the strong coupling regime of protons. Described here is a consolidated pulse sequence that achieves this transformation of singlet-state spin order into heteronuclear magnetization across a wide range of scalar couplings in AA'X spin systems. Analytic solutions to the spin evolution are presented, and performance was validated experimentally in the parahydrogen addition product, 2-hydroxyethyl 1-C-13-propionate-d(3). Hyperpolarized carbon-13 signals were enhanced by a factor of several million relative to Boltzmann polarization in a static magnetic field of 47.5 mT (similar to 13% polarization). We anticipate that this pulse sequence will provide efficient conversion of parahydrogen spin order over a broad range of emerging PHIP agents that feature AA'X spin systems.