Cardiac metabolic imaging using hyperpolarized [1-13C]lactate as a substrate

Abstract

Hyperpolarized [1-13C]lactate is an attractive alternative to [1-13C]pyruvate as a substrate to investigate cardiac metabolism in vivo; it can be administered safely at a higher dose and can be polarized to a similar degree as pyruvate via dynamic nuclear polarization. While 13C cardiac experiments using HP lactate have been performed in small animal models, it has not been demonstrated in large animal models or humans. Utilizing the same hardware and data acquisition methods used in the first human HP 13C cardiac study, 13C metabolic images were acquired following injections of HP [1-13C]lactate in porcine hearts. Data were also acquired using HP [1-13C]pyruvate for comparison. The 13C bicarbonate signal was localized to the myocardium and had a similar appearance with both substrates for all animals. No 13C pyruvate signal was detected in the experiments following injection of hyperpolarized 13C lactate. The SNR of injected lactate was 88 +/-14% of the SNR of injected pyruvate, and the SNR of bicarbonate in the experiments using lactate as the substrate was 52+/-19% of the SNR in the experiments using pyruvate as the substrate. The lower SNR was likely due to the shorter T1 of [1-13C]lactate as compared to [1-13C]pyruvate and the additional enzyme-catalyzed metabolic conversion step before the 13C nuclei from [1-13C]lactate were detected as 13C bicarbonate. While challenges remain, the potential of HP lactate as a substrate for clinical metabolic imaging of human heart was demonstrated.

Regional quantification of cardiac metabolism with hyperpolarized [1-13C]-pyruvate CMR evaluated in an oral glucose challenge

“…This potentially has an impact on all hyperpolarized 13 C-pyruvate studies, as it implies that the 13 C-lactate observed can be coming from blood pool metabolic conversion instead of the tissue of interest. This circulating 13 C-lactate could also be a source of contrast as it can be used as a fuel source [ 30 – 32 ]. It will also introduce partial volume errors in voxels containing myocardium and blood pool, originating from the chambers and potentially coronary arteries, where the additional blood lactate would likely increase the 13 C-lactate/pyruvate and k PL .…”

Regional quantification of cardiac metabolism with hyperpolarized [1 -13C]-pyruvate MRI evaluated in an oral glucose challenge

“…This potentially has an impact on all hyperpolarized 13 C-pyruvate studies, as it implies that the 13 C-lactate observed can be coming from blood pool metabolic conversion instead of the tissue of interest. This circulating 13 C-lactate could also be a source of contrast as it can be used as a fuel source [30][31][32] . It will also introduce partial volume errors in voxels containing myocardium and blood pool, originating from the chambers and potentially coronary arteries, where the additional blood lactate would likely increase the 13 Clactate/pyruvate and k PL .…”