Probing hepatic metabolism of [2-13C]dihydroxyacetone in vivo with 1H-decoupled hyperpolarized 13C-MR
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,...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Springer
2020
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| _version_ | 1797080724204945408 |
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| author | Marco-Rius, I Wright, AJ Hu, D-E Savic, D Miller, JJ Timm, KN Tyler, D Brindle, KM Comment, A |
| author_facet | Marco-Rius, I Wright, AJ Hu, D-E Savic, D Miller, JJ Timm, KN Tyler, D Brindle, KM Comment, A |
| author_sort | Marco-Rius, I |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T01:04:14Z |
| format | Journal article |
| id | oxford-uuid:8ac53e8a-e14e-4652-b7d4-8ab6a0f5219f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:04:14Z |
| publishDate | 2020 |
| publisher | Springer |
| record_format | dspace |
| spelling | oxford-uuid:8ac53e8a-e14e-4652-b7d4-8ab6a0f5219f2022-03-26T22:33:46ZProbing hepatic metabolism of [2-13C]dihydroxyacetone in vivo with 1H-decoupled hyperpolarized 13C-MRJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8ac53e8a-e14e-4652-b7d4-8ab6a0f5219fEnglishSymplectic ElementsSpringer2020Marco-Rius, IWright, AJHu, D-ESavic, DMiller, JJTimm, KNTyler, DBrindle, KMComment, AOBJECTIVES: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. |
| spellingShingle | Marco-Rius, I Wright, AJ Hu, D-E Savic, D Miller, JJ Timm, KN Tyler, D Brindle, KM Comment, A Probing hepatic metabolism of [2-13C]dihydroxyacetone in vivo with 1H-decoupled hyperpolarized 13C-MR |
| title | Probing hepatic metabolism of [2-13C]dihydroxyacetone in vivo with 1H-decoupled hyperpolarized 13C-MR |
| title_full | Probing hepatic metabolism of [2-13C]dihydroxyacetone in vivo with 1H-decoupled hyperpolarized 13C-MR |
| title_fullStr | Probing hepatic metabolism of [2-13C]dihydroxyacetone in vivo with 1H-decoupled hyperpolarized 13C-MR |
| title_full_unstemmed | Probing hepatic metabolism of [2-13C]dihydroxyacetone in vivo with 1H-decoupled hyperpolarized 13C-MR |
| title_short | Probing hepatic metabolism of [2-13C]dihydroxyacetone in vivo with 1H-decoupled hyperpolarized 13C-MR |
| title_sort | probing hepatic metabolism of 2 13c dihydroxyacetone in vivo with 1h decoupled hyperpolarized 13c mr |
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