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Singlet-contrast magnetic resonance imaging: unlocking hyperpolarization with metabolism

revised on 09.09.2020 and posted on 10.09.2020 by James Eills, Eleonora Cavallari, Raphael Kircher, Ginevra Di Matteo, Carla Carrera, Laurynas Dagys, Malcolm H. Levitt, Konstantin Ivanov, Silvio Aime, Francesca Reineri, Kerstin Münnemann, Dmitry Budker, Gerd Buntkowsky, Stephan Knecht
Hyperpolarization-enhanced magnetic resonance imaging can be used to study biomolecular processes in the body, but typically requires nuclei such as 13C, 15N, or 129Xe 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 1H 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 D2O. 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 1H‑imaging modality presented here can allow for hyperpolarized imaging without the need for low‑abundance, low‑sensitivity heteronuclei.


Zero and ultra-low field nuclear magnetic resonance

European Commission

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Functionalized Magnetic Resonance Beacons for Enhanced Spectroscopy and Imaging

European Research Council

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Athenaeum Research 2016, CSTO164550

DFG grant number BU 911/22-2

DFG grant number BU 911/29-1

Development and Application of Novel Parahydrogen based NMR Techniques

Russian Science Foundation

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Email Address of Submitting Author


Johannes Gutenberg Universität Mainz



ORCID For Submitting Author


Declaration of Conflict of Interest

The authors declare no conflict of interest.



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