Dynamic ¹H‐MRS for detection of ¹³C‐labeled glucose metabolism in the human brain at 3T

Abstract

Purpose: In 2004, Boumezbeur et al proposed a simple yet powerful approach to detect the metabolism of 13 C-enriched substrates in the brain. Their approach consisted of dynamic 1 H-MRS, without a 13 C radiofrequency (RF) channel, and its successful application was demonstrated in monkeys. Since then, this promising method has yet to be applied rigorously in humans. In this study, we revisit the use of dynamic 1 H-MRS to measure the metabolism of 13 C-enriched substrates and demonstrate its application in the human brain. Methods: In healthy participants, 1 H-MRS data were acquired dynamically before and following a bolus infusion of [1-13 C] glucose. Data were acquired on a 3T clinical MRI scanner using a short-TE SPECIAL sequence, with regions of interest in both anterior and posterior cingulate cortex. Using simulated basis spectra to model signal changes in both 12 C-bonded and 13 C-coupled resonances, the acquired spectra were fit in LCModel to obtain labeling time courses for glutmate and glutamine at both C4 and C3 positions. Results: Presence of the 13 C label was clearly detectable, owing to the pronounced effect of heteronuclear ( 13 C-1 H) scalar coupling on the observed 1 H spectra. A decrease in signal from 12 C-bonded protons and an increase in signal from 13 C-coupled protons were observed. The fractional enrichment of Glu-C4, (Glu+Gln)-C4, and (Glu+Gln)-C3 at 30 minutes following infusion of [1-13 C] glucose was similar in both regions: 11% to 13%, 9% to 12% and 3% to 5%, respectively. Conclusion: These preliminary results confirm the feasibility of the use of dynamic 1 H-MRS to monitor 13 C labeling in the human brain, without a 13 C RF channel.[Correction added after online publication 8 February, 2020. The "Measured Spectra" in Figure 6b has been corrected to display the full peak-to-peak spectral range.] | 1141

Dynamic observation of2H labeled compounds in the human brain with1H versus2H magnetic resonance spectroscopy at 9.4T

“…27 Other studies that reported fractional enrichments used infusion of [1- 13 C]-glucose. These studies reported maximal enrichment of 15 % to 30 % 26,[31][32][33][34][35] . The value measured in this study is in a similar range.…”

Metabolic analysis in intact human-derived cerebral organoids by high-resolution magic-angle spinning NMR spectroscopy

“…This approach had the advantage that it enabled quantification of the metabolic rate of LDH activity. In the future, we hope to extend our approach to enable similar quantitative metabolic flux measures in hESC-derived COs using indirect 13 C-or 2 Hlabelled glucose administration, as demonstrated previously in in vivo magnetic resonance spectroscopy (MRS) studies [14][15][16][17] . Lastly, van der Kemp et al 18 reported a comparison between HR-MAS NMR spectroscopy of intact colorectal cancer organoids, and solution NMR spectroscopy of polar extracts.…”

Hadamard‐encoded dual‐voxel SPECIAL: Short‐TE MRS acquired in two brain regions simultaneously using Hadamard encoding

“…Thus, relative to consecutive SV-MRS measurements in two VOIs, HD-SPECIAL reduces the total scan time twofold with minimal SNR loss and with minimal penalty in terms of spectral quality. In the case of dynamic measurement of metabolites with multiple VOIs, such as 13 C labeling studies 39 or functional MRS studies, 40 simultaneous measurement from two regions may be scientifically preferable, increasing the available temporal resolution by a factor of two.…”