Overcoming the Challenges of Hyperpolarizing Substrates with Parahydrogen-Induced Polarization in an MRI System

Hyperpolarization of ¹³C nuclei in biomolecules and their administration as imaging agents enables in-vivo monitoring of metabolism. This approach has demonstrated potential for deriving imaging biomarkers for cancer detection, differentiation, and therapy efficacy assessment. The in situ generation of polarized substrates using a permanent addition of parahydrogen to an unsaturated precursor inside the bore of an MRI system used for subsequent imaging circumvents the need for a dedicated external polarizer. This approach reduces polarization loss associated with sample transfer, minimizes hardware requirements and cost, and results in reduced spatial requirements. However, performing INEPT-like pulsed sequences for heteronuclear spin-order transfer in the bore of an MRI system is challenged by poor uniformity of static and excitation magnetic field and molecular convection during the polarization transfer. Therefore, here we characterize these effects, implement a robust modification to the pulse sequence, and measure experimentally the polarization improvement upon modification of the sequence. After rigorous optimization of the parameters, we obtained a ¹³C polarization of 44.5 % for 50 mM of the 1-¹³C site of ethyl acetate-d₆. Our parahydrogen-induced polarization approach enhances the accessibility to hyperpolarized MRI, circumventing the need for an external polarizer.