Brain metabolism under different anesthetic conditions using hyperpolarized [1‐¹³C]pyruvate and [2‐¹³C]pyruvate

Abstract

Carbon-13 NMR spectroscopy (13C MRS) offers the unique capability to measure brain metabolic rates in vivo. Hyperpolarized 13C reduces the time required to assess brain metabolism from hours to minutes compared to conventional 13C MRS. This study investigates metabolism of hyperpolarized [1-13C]pyruvate and [2-13C]pyruvate in the rat brain in vivo under various anesthetics: pentobarbital, isoflurane, α-chloralose, and morphine. The apparent metabolic rate from pyruvate to lactate modeled using time courses obtained after injection of hyperpolarized [1-13C]pyruvate was significantly greater for isoflurane than for all other anesthetic conditions, and significantly greater for morphine than for α-chloralose. The apparent metabolic rate from pyruvate to bicarbonate was significantly greater for morphine than for all other anesthetic conditions, and significantly lower for pentobarbital than for α-chloralose. Results show that relative TCA rates determined from hyperpolarized 13C data are consistent with TCA cycle rates previously measured using conventional 13C MRS under similar anesthetic conditions, and that using morphine for sedation greatly improves detection of downstream metabolic products compared to other anesthetics.

Measuring Glycolytic Activity with Hyperpolarized [2H7, U-13C6] D-Glucose in the Naive Mouse Brain under Different Anesthetic Conditions

“…A recent HP 13 C MRS study with HP [1- 13 C] Pyr at different brain consciousness states demonstrated that the conversion rate of Pyr to bicarbonate is consistent with the TCA cycle rate determined from non-HP experiments and corresponds to what is expected under different anesthetic conditions [ 43 ]. However, when using HP [1- 13 C] Pyr, the conversion rates of Pyr to Lac did not change significantly under different anesthetic conditions [ 43 ]. HP Pyr experiments are capable to probe only a specific portion of the Glc metabolism.…”

The metabolic representation of ischemia in rat brain slices: A hyperpolarized 13C magnetic resonance study

“…In addition, confounding factors concerning in vivo rodent experiments involve the blood-brain-barrier (BBB) transport kinetics via monocarboxylate transporters, 52 and their dependence on the anesthesia used. 21,26,28 Ex vivo, the BBB is severed and thus the arrival of hyperpolarized [1- 13 C] pyruvate to the cells is likely faster, as is the case for a disturbed BBB in vivo. 34 In a previous study using a similar ex vivo preparation we used a conventional small flip angle acquisition approach to collect the data.…”

“…8,9,14 Hyperpolarized [1- 13 C]pyruvate has been previously used to observe rapid metabolic processes in many promising applications. [16][17][18][19] Specifically, real-time brain metabolism was investigated in vivo in small animals [20][21][22][23][24][25][26][27][28][29][30] and, relating to stroke, 31,32 in the human brain 10,[33][34][35][36] and in the rat brain ex vivo. 5 In the current study, hyperpolarized [1- 13 C]pyruvate was also used as the metabolic substrate.…”

LDH and PDH Activities in the Ischemic Brain and the Effect of Reperfusion—An Ex Vivo MR Study in Rat Brain Slices Using Hyperpolarized [1-13C]Pyruvate

“…Hyperpolarized [1- 13 C]pyruvate has been previously used to observe rapid metabolic processes in many promising applications [ 27 , 28 , 29 , 30 ]. Specifically, real-time brain metabolism was investigated in vivo in small animals [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ], in small animal models related to stroke [ 42 , 43 ], in the human brain [ 25 , 44 , 45 ], and in the rat brain ex vivo [ 46 ].…”