Quasi-continuous production of highly hyperpolarized carbon-13 contrast agents every 15 seconds within an MRI system

Magnetic resonance imaging of hyperpolarized contrast agents has enabled unprecedented imaging capabilities in a biomedical setting, but its widespread application is hindered by the time and costs associated with preparing hyperpolarized carbon-13 samples. Here, the authors demonstrate virtually-continuous production of batches of highly-hyperpolarized carbon-13 contrast agents every 15 s within an MRI system without a stand-alone polarizer. Hyperpolarized contrast agents (HyCAs) have enabled unprecedented magnetic resonance imaging (MRI) of metabolism and pH in vivo. Producing HyCAs with currently available methods, however, is typically time and cost intensive. Here, we show virtually-continuous production of HyCAs using parahydrogen-induced polarization (PHIP), without stand-alone polarizer, but using a system integrated in an MRI instead. Polarization of approximate to 2% for [1-C-13]succinate-d(2) or approximate to 19% for hydroxyethyl-[1-C-13]propionate-d(3) was created every 15 s, for which fast, effective, and well-synchronized cycling of chemicals and reactions in conjunction with efficient spin-order transfer was key. We addressed these challenges using a dedicated, high-pressure, high-temperature reactor with integrated water-based heating and a setup operated via the MRI pulse program. As PHIP of several biologically relevant HyCAs has recently been described, this Rapid-PHIP technique promises fast preclinical studies, repeated administration or continuous infusion within a single lifetime of the agent, as well as a prolonged window for observation with signal averaging and dynamic monitoring of metabolic alterations.

Automated summary

This study demonstrates the virtually continuous production of highly-hyperpolarized carbon-13 contrast agents within an MRI system every 15 seconds, without the need for a stand-alone polarizer. The authors addressed the challenges of efficient spin-order transfer and synchronized cycling of chemicals and reactions to achieve polarization levels of approximately 2% and 19% for various contrast agents. This Rapid-PHIP technique promises fast preclinical studies and repeated administration.