Doublet asymmetry for estimating polarization in hyperpolarized 13 C-pyruvate studies.

Hyperpolarized 13 C MRS allows in vivo interrogation of key metabolic pathways, with pyruvate (Pyr) the substrate of choice for current clinical studies. Knowledge of the liquid-state polarization is needed for full quantitation, and asymmetry of the C2 doublet, arising from 1% naturally abundant [1,2-13 C]Pyr in any hyperpolarized [1-13 C]Pyr sample, has been suggested as a direct measure of in vivo C1 polarization via the use of an in vitro calibration curve. Here we show that different polarization levels can yield the same C2 -doublet asymmetry, thus limiting the utility of this metric for quantitation. Furthermore, although the time evolution of doublet asymmetry is poorly modeled using the expected dominant relaxation mechanisms of carbon-proton dipolar coupling and chemical shift anisotropy, the inclusion of a C-C dipolar coupling term can explain the observed initial evolution of the C2 doublet asymmetry beyond its expected thermal equilibrium value.