Rapid and simple 13C-hyperpolarization by 1H dissolution dynamic nuclear polarization followed by an in-line magnetic field inversion

Dissolution dynamic nuclear polarization (dDNP) is a method of choice for preparing hyperpolarized 13C metabolites such as [1-13C]-pyruvate used for in vivo applications including the real-time monitoring of cancer cell metabolism in human patients. The approach consists of transferring the high polarization of electron spins to nuclear spins via microwave irradiation at low temperatures (1.0-1.5 K) and moderate magnetic fields (3.3-7 T). The solid sample is then dissolved and transferred to an NMR spectrometer or MRI scanner for detection in the liquid state. Common dDNP protocols use direct hyperpolarization of13C spins reaching polarizations of >50% in ~1-2 hours. Alternatively, 1H spins are polarized before transferring their polarization to 13C spins using cross-polarization (CP), reaching similar polarization levels as direct DNP in only ~20 min. However, it relies on more complex instrumentation, requiring highly skilled personnel. Here, we explore an alternative route using 1H dDNP followed by an inline adiabatic magnetic field inversion in the liquid state during the transfer. 1H polarizations of >70% in the solid-state are obtained in ~5-10 min. As the hyperpolarized sample travels from the dDNP polarizer to the NMR spectrometer, it goes through a field inversion chamber, which causes 1H→13C polarization transfer. This transfer is made possible by the J-coupling between the heteronuclei, which mixes the Zeeman states at zero-field and causes an anti-level crossing. We report liquid-state 13C polarization up to ~17% for [3-13C]-pyruvate and 13C-formate. The instrumentation needed to perform this experiment in addition to a conventional dDNP polarizer is simple and readily assembled.