Probing hepatic metabolism of [2- 13 C]dihydroxyacetone in vivo with 1 H-decoupled hyperpolarized 13 C-MR
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RESEARCH ARTICLE
Probing hepatic metabolism of [2‑13C]dihydroxyacetone in vivo with 1H‑decoupled hyperpolarized 13C‑MR Irene Marco‑Rius1,6 · Alan J. Wright1 · De‑en Hu1 · Dragana Savic2,4 · Jack J. Miller2,3,4 · Kerstin N. Timm2 · Damian Tyler2,4 · Kevin M. Brindle1 · Arnaud Comment1,5 Received: 1 June 2020 / Revised: 7 August 2020 / Accepted: 27 August 2020 © The Author(s) 2020
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. Keywords Carbon-13 magnetic resonance spectroscopy · Gluconeogenesis · Glycolysis · Liver · Metabolism · Dynamic Nuclear Polarisation · Hyperpolarisation
Introduction
Irene Marco-Rius and Alan Wright have contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10334-020-00884-y) contains supplementary material, which is available to authorized users. * Irene Marco‑Rius [email protected] 1
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
2
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK
3
Clarendon Laboratory, Department of Physics, University of Oxford, Oxford, UK
The human liver performs a broad range of tasks that affect the function of the whole body, from maintaining plasma glucose homeostasis to filtering toxic chemicals from food and drinks [1]. In most cases, the liver can regenerate after an insult and recover functionality. However, recurrent
4
Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Division of Medicine, University of Oxfor
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