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Probing hepatic metabolism of [2-13C]dihydroxyacetone in vivo with 1H-decoupled hyperpolarized 13C-MR

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.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1007/s10334-020-00884-y

Authors

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Role:
Author
ORCID:
0000-0001-5076-8526
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Institution:
University of Oxford
Division:
MSD
Department:
Physiology Anatomy & Genetics
Role:
Author
ORCID:
0000-0002-6258-1299


Publisher:
Springer
Journal:
Magnetic Resonance Materials in Physics, Biology and Medicine More from this journal
Volume:
34
Pages:
49-56
Publication date:
2020-09-10
Acceptance date:
2020-08-27
DOI:
EISSN:
1352-8661
ISSN:
0968-5243
Pmid:
32910316


Language:
English
Keywords:
Pubs id:
1132011
Local pid:
pubs:1132011
Deposit date:
2020-11-25
ARK identifier:

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