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- Title
Probing hepatic metabolism of [2-13C]dihydroxyacetone in vivo with 1H-decoupled hyperpolarized 13C-MR.
- Authors
Marco-Rius, Irene; Wright, Alan J.; Hu, De-en; Savic, Dragana; Miller, Jack J.; Timm, Kerstin N.; Tyler, Damian; Brindle, Kevin M.; Comment, Arnaud
- Abstract
Objectives: To enhance detection of the products of hyperpolarized [2-13C]dihydroxyacetone metabolism for assessment of three metabolic pathways in the liver in vivo. Hyperpolarized [2-13C]DHAc emerged as a promising substrate to follow gluconeogenesis, glycolysis and the glycerol pathways. However, the use of [2-13C]DHAc in vivo has not taken off because (i) the chemical shift range of [2-13C]DHAc and its metabolic products span over 144 ppm, and (ii) 1H decoupling is required to increase spectral resolution and sensitivity. While these issues are trivial for high-field vertical-bore NMR spectrometers, horizontal-bore small-animal MR scanners are seldom equipped for such experiments. Methods: Real-time hepatic metabolism of three fed mice was probed by 1H-decoupled 13C-MR following injection of hyperpolarized [2-13C]DHAc. The spectra of [2-13C]DHAc and its metabolic products were acquired in a 7 T small-animal MR scanner using three purpose-designed spectral-spatial radiofrequency pulses that excited a spatial bandwidth of 8 mm with varying spectral bandwidths and central frequencies (chemical shifts). Results: The metabolic products detected in vivo include glycerol 3-phosphate, glycerol, phosphoenolpyruvate, lactate, alanine, glyceraldehyde 3-phosphate and glucose 6-phosphate. The metabolite-to-substrate ratios were comparable to those reported previously in perfused liver. Discussion: Three metabolic pathways can be probed simultaneously in the mouse liver in vivo, in real time, using hyperpolarized DHAc.
- Subjects
DIHYDROXYACETONE; SPECTRAL sensitivity; METABOLISM; NMR spectrometers; DYNAMIC nuclear polarisation; ALANINE
- Publication
MAGMA: Magnetic Resonance Materials in Physics, Biology & Medicine, 2021, Vol 34, Issue 1, p49
- ISSN
0968-5243
- Publication type
Article
- DOI
10.1007/s10334-020-00884-y