Parahydrogen-induced 13C hyperpolarizer using a flow guide for magnetic field cycling to evoke 1H-13C spin order transfer toward metabolic MRI

Objective: The pair-wise addition of parahydrogen, the singlet form of molecular hydrogen, to unsaturated precursors evokes the hyperpolarization of two parahydrogen-derived 1H nuclear spins through a process known as parahydrogen-induced polarization (PHIP). Subsequent spin order transfer (SOT) from the 1H to the surrounding 13C nuclear spins via magnetic field cycling (MFC) results in substantial signal enhancement in 13C magnetic resonance imaging (MRI). Here, we report the development of a unique PHIP
¹³
C hyperpolarizer system using a flow guide for MFC. Methods: The optimal MFC scheme for 1H to 13C spin order transfer was quantum-chemically simulated using the J-coupling values of 13C-labeled metabolic tracers. The flow guide system was three-dimensionally designed based on the simulated MFC scheme and pre-measured magnetic field distribution in a zero-field chamber. Results: The system efficiently transfers the spin order of hyperpolarized 1H to a particular 13C spin when the parahydrogenated tracer passes through the flow guide at a designated flow rate. The 13C MRI signal is enhanced more than 40,000 times in 13C-labeled pyruvate and fumarate, compared to the thermal equilibrium level at 1.5 T, was achieved for conducting in vivo metabolic MRI of mice. Conclusion: A fully automated PHIP-based 13C polarizer was developed using a unique flow guide to conduct the MFC for 1H to 13C SOT. Significance: The PHIP hyperpolarizer with a flow guide can conduct efficient 1H-13C SOT without a MFC magnetic field sweep system and offers a cost-effective alternative to conventional dynamic nuclear polarization.