Exploring Limits of [1-¹³C]Pyruvate Nuclear Spin Relaxation: Impact of Field, Deuteration, Degassing, and Additives

Limited lifetime is the most prominent hurdle for hyperpolarized magnetic resonance imaging. Today, [1-¹³C]pyruvate is the most widely used metabolic hyperpolarized probe, but low signal-to-noise ratio (SNR) for metabolites such as lactate remains a critical challenge. As post-administration relaxation is difficult to affect, reducing polarization losses during delivery, purification, and administration is key for increasing SNR. To elucidate the relaxation mechanisms governing [1-¹³C]pyruvate T ₁, we evaluate 35 sample compositions across magnetic fields from a few µT to 9.4 T, varying solvent and agent deuteration, buffer type and concentration, degassing, and additives. Field-dependent T ₁ profiles reveal distinct mechanistic contributions from each factor, with degassing and deuteration exerting the strongest effects at low fields relevant to clinical transfer conditions. Notably, buffer composition has an unexpected and substantial impact on T ₁, a finding largely overlooked in prior literature. Under optimized conditions, [1-¹³C]pyruvate T ₁ at Earth's field is extended by almost 8 times, from ~30 to ~230 s. This reduces polarization losses after a 20-60 s transfer interval by 3.6-5.6-fold, thus increasing SNR. These findings are also important for hyperpolarized probes beyond pyruvate, which exhibit faster low-field relaxation and stand to benefit even more substantially from systematic control of sample composition.