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.