Oxidation of [U‐¹³C]glucose in the human brain at 7T under steady state conditions

Abstract

Purpose Disorders of brain energy metabolism and neurotransmitter recycling have been implicated in multiple neurological conditions. 13C Magnetic Resonance Spectroscopy (MRS) during intravenous administration of 13C-labeled compounds has been used to measure turnover rates of brain metabolites. This approach, however, requires prolonged infusion inside the magnet. Proton decoupling is typically required but may be difficult to implement with standard equipment. We examined an alternative approach to monitor glucose metabolism in human brain. Methods 13C-enriched glucose was infused in healthy subjects outside the magnet to a steady-state level of 13C enrichment. Subsequently, the subjects were scanned at 7T for 60 min, without 1H decoupling. Metabolic modelling was used to calculate anaplerosis. Results Biomarkers of energy metabolism and anaplerosis were detected. The glutamate C5 doublet provided information about glucose-derived acetyl-CoA flux into the TCA cycle via pyruvate dehydrogenase, while the bicarbonate signal reflected overall TCA cycle activity. The glutamate C1/C5 ratio is sensitive to anaplerosis. Conclusions Brain 13C MRS at 7T provides information about glucose oxidation and anaplerosis without the need of prolonged 13C infusions inside the scanner and without technical challenges of 1H decoupling, making it a feasible approach for clinical research.

Selective proton‐observed, carbon‐edited (selPOCE) MRS method for measurement of glutamate and glutamine 13C‐labeling in the human frontal cortex

“…1a) is based on 1.0-ms asymmetric Shinnar-Le Roux excitation pulses (6.1 kHz bandwidth) (19) The traditional STEAM mixing time is used to play out various pulse-sequence elements to provide distinction between 13 C-labeled and unlabeled compounds (b, c) and between compounds with different 13 C chemical shifts (d, e). Protons attached to 12 C and 13 C are separated by subtracting signal acquired with a 13 C inversion pulse (c) from that acquired without any 13 C pulses (b). Compounds with a Dn chemical shift difference (in hertz) can be separated through evolution over a time period 1/2Dn followed by a 13 C excitation pulse along the þx (d) or -x (e) axis.…”

“…Detection of 13 C-labeling in brain metabolites using 13 C magnetic resonance spectroscopy (MRS) during administration of a 13 C-labeled substrate (e.g., [1][2][3][4][5][6][7][8][9][10][11][12][13] C]-glucose) is a powerful, noninvasive method for quantifying rates of metabolism and glutamate/glutamine (Glu/Gln) neurotransmitter cycling in the brain (1,2). In vivo 13 C MRS methods can be classified as either direct or indirect detection techniques.…”

“…There are few reports of 1 H-[ 13 C] MRS applications in human brain, mostly limited to acquisitions in the occipital lobe (7)(8)(9), with some application in other brain regions emphasized on the detection of labeling in Glu (10,11). Due to concerns about RF heating and difficulties in obtaining adequate B 0 homogeneity, applications of 13 C MRS in the frontal lobe of human brain have relied on direct 13 C MRS and 13 C-labeling strategies that enrich the carboxylic carbons (12)(13)(14)(15). The carboxylic carbons can be detected without localization schemes, as peaks of natural abundance lipids do not overlap with the Glu and Gln peaks.…”

“…Furthermore, decoupling the long-range 1 H-13 C couplings of the carboxylic carbons can be achieved with low RF power (14). This robust, direct 13 C MRS technique can also be applied at 7 T with (16) or without low power decoupling (12).…”

“…The difference spectrum shows the 1 H signals bound to a 13 C nucleus, which only occurs for the 1.1% natural abundance of Glu and Gln. Note that even though 1 H-[12 C] and 1 H-[ 13 C] signals are effectively separated, [4-13 C]-Glu-H4 and [4-13 C]-Gln-H4 are still strongly overlapping. c: Difference 1 H MR spectrum between the data acquired with a heteronuclear single-quantum coherence module optimized for [4-13 C]-Glu-H4 and [4-13 C]-Gln-H4 phase modulation.…”