Parahydrogen-Induced ¹³C Hyperpolarizer Using a Flow Guide for Magnetic Field Cycling to Evoke ¹H-¹³C Spin Order Transfer Toward Metabolic MRI.

Abstract

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 ¹³C hyperpolarizer system using a flow guide for MFC. 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. 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. A fully automated PHIP-based ¹³C polarizer was developed using a unique flow guide to conduct the MFC for ¹H to ¹³C SOT. 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.