Proton-Only Sensing of Hyperpolarized [1,2-C]Pyruvate

Hyperpolarized MRI is emerging as a next-generation molecular imaging modality that can detect metabolic transformations in real time deep inside tissue and organs. C-hyperpolarized pyruvate is the leading hyperpolarized contrast agent that can probe cellular energetics in real time. Currently, hyperpolarized MRI requires specialized "multinuclear" MRI scanners that have the ability to excite and detect C signals. The objective of this work is the development of an approach that works on conventional (i.e., proton-only) MRI systems while taking advantage of long-lived C hyperpolarization. The long-lived singlet state of [1,2-C]pyruvate is hyperpolarized with parahydrogen in reversible exchange, and subsequently, the polarization is transferred from the C spin pair to the methyl protons of pyruvate for detection. This polarization transfer is accomplished with spin-lock induced crossing pulses that are only applied to the methyl protons yet access the hyperpolarization stored in the C singlet state. Theory and first experimental demonstrations are provided for our method, which obviates C excitation and detection for proton sensing of C-hyperpolarized pyruvate with an overall experimental-polarization transfer efficiency of ∼22% versus a theoretically predicted polarization transfer efficiency of 25%.