Lactate saturation limits bicarbonate detection in hyperpolarized C-13-pyruvate MRI of the brain

Purpose To investigate the potential effects of [1-C-13]lactate RF saturation pulses on [C-13]bicarbonate detection in hyperpolarized [1-C-13]pyruvate MRI of the brain. Methods Thirteen healthy rats underwent MRI with hyperpolarized [1-C-13]pyruvate of either the brain (n = 8) or the kidneys, heart, and liver (n = 5). Dynamic, metabolite-selective imaging was used in a cross-over experiment in which [1-C-13]lactate was excited with either 0 degrees or 90 degrees flip angles. The [C-13]bicarbonate SNR and apparent [1-C-13]pyruvate-to-[C-13]bicarbonate conversion (k(PB)) were determined. Furthermore, simulations were performed to identify the SNR optimal flip-angle scheme for detection of [1-C-13]lactate and [C-13]bicarbonate. Results In the brain, the [C-13]bicarbonate SNR was 64% higher when [1-C-13]lactate was not excited (5.8 +/- 1.5 vs 3.6 +/- 1.3; 1.2 to 3.3-point increase; p = 0.0027). The apparent k(PB) decreased 25% with [1-C-13]lactate saturation (0.0047 +/- 0.0008 s(-1) vs 0.0034 +/- 0.0006 s(-1); 95% confidence interval, 0.0006-0.0019 s(-1) increase; p = 0.0049). These effects were not present in the kidneys, heart, or liver. Simulations suggest that the optimal [C-13]bicarbonate SNR with a TR of 1 s in the brain is obtained with [C-13]bicarbonate, [1-C-13]lactate, and [1-C-13]pyruvate flip angles of 60 degrees, 15 degrees, and 10 degrees, respectively. Conclusions Radiofrequency saturation pulses on [1-C-13]lactate limit [C-13]bicarbonate detection in the brain specifically, which could be due to shuttling of lactate from astrocytes to neurons. Our results have important implications for experimental design in studies in which [C-13]bicarbonate detection is warranted.