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

To investigate the potential effects of [1-¹³ C]lactate RF saturation pulses on [¹³ C]bicarbonate detection in hyperpolarized [1-¹³ C]pyruvate MRI of the brain.

Thirteen healthy rats underwent MRI with hyperpolarized [1-¹³ C]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 [1-¹³ C]lactate was excited with either 0° or 90° flip angles. The [¹³ C]bicarbonate SNR and apparent [1-¹³ C]pyruvate-to-[¹³ C]bicarbonate conversion (k_PB ) were determined. Furthermore, simulations were performed to identify the SNR optimal flip-angle scheme for detection of [1-¹³ C]lactate and [¹³ C]bicarbonate.

In the brain, the [¹³ C]bicarbonate SNR was 64% higher when [1-¹³ C]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 [1-¹³ C]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 [¹³ C]bicarbonate SNR with a TR of 1 s in the brain is obtained with [¹³ C]bicarbonate, [1-¹³ C]lactate, and [1-¹³ C]pyruvate flip angles of 60°, 15°, and 10°, respectively.

Radiofrequency saturation pulses on [1-¹³ C]lactate limit [¹³ C]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 [¹³ C]bicarbonate detection is warranted.