Repeatability of Metabolic Imaging With Hyperpolarized Pyruvate: Back-to-Back Neuroimaging and Blood Analysis

¹³C MRI with hyperpolarized [1-¹³C]pyruvate enables noninvasive imaging of metabolic pathways. Considering the high dose of pyruvate used in hyperpolarized ¹³C-pyruvate studies, circulating ¹³C-pyruvate and the resulting ¹³C-lactate in plasma may influence subsequent pyruvate metabolism, yet the guidance on consecutive injections does not exist. This study is to characterize blood pyruvate and lactate dynamics following [1-¹³C]pyruvate injection and to evaluate the repeatability of ¹³C neuroimaging with consecutive pyruvate injections.

Sixteen healthy adults (mean age, 39.0 ± 15.9 years; 8 men) underwent blood sampling or MRI. Eight participants received bolus injections of non-hyperpolarized [1-¹³C]pyruvate following both overnight fasting and postprandial states. Blood samples were collected at baseline and up to 60 min post-injection to quantify pyruvate and lactate concentrations and ¹³C fractional enrichments using mass spectrometry. In parallel, eight participants underwent ¹³C/¹H MRI that included two injections of hyperpolarized [1-¹³C]pyruvate with intervals of 6-55 min for time-resolved measurement of ¹³C-pyruvate and ¹³C-lactate in the brain.

Plasma ¹³C-pyruvate peaked within 30 s and returned to baseline within 5-10 min, while ¹³C-lactate peaked at 2-3 min. Lactate ¹³C enrichment was higher in fasting versus fed states, and total lactate concentration in blood was unchanged by pyruvate injection. Brain ¹³C-lactate/pyruvate showed excellent repeatability (ICC = 0.9842), with all points within the 95% Bland-Altman limits. Voxel-wise Pearson's correlation between injections was 0.72 ± 0.22 and within-subject coefficient of variation was 17.6% ± 4.6%.

Consecutive injections of hyperpolarized [1-¹³C]pyruvate yield repeatable blood and brain metabolic measurements in humans, supporting multi-injection protocols in ¹³C MRI studies.