Singlet‐Contrast Magnetic Resonance Imaging: Unlocking Hyperpolarization with Metabolism

Hyperpolarization‐enhanced magnetic resonance imaging can be used to study biomolecular processes in the body, but typically requires nuclei such as (13)C, (15)N, or (129)Xe due to their long spin‐polarization lifetimes and the absence of a proton‐background signal from water and fat in the images. Here we present a novel type of (1)H imaging, in which hyperpolarized spin order is locked in a nonmagnetic long‐lived correlated (singlet) state, and is only liberated for imaging by a specific biochemical reaction. In this work we produce hyperpolarized fumarate via chemical reaction of a precursor molecule with para‐enriched hydrogen gas, and the proton singlet order in fumarate is released as antiphase NMR signals by enzymatic conversion to malate in D(2)O. Using this model system we show two pulse sequences to rephase the NMR signals for imaging and suppress the background signals from water. The hyperpolarization‐enhanced (1)H‐imaging modality presented here can allow for hyperpolarized imaging without the need for low‐abundance, low‐sensitivity heteronuclei.