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High-resolution hyperpolarized in vivo metabolic 13C spectroscopy at low magnetic field (48.7mT) following murine tail-vein injection.

ABSTRACT: High-resolution 13C NMR spectroscopy of hyperpolarized succinate-1-13C-2,3-d2 is reported in vitro and in vivo using a clinical-scale, biplanar (80cm-gap) 48.7mT permanent magnet with a high homogeneity magnetic field. Non-localized 13C NMR spectra were recorded at 0.52MHz resonance frequency over the torso of a tumor-bearing mouse every 2s. Hyperpolarized 13C NMR signals with linewidths of ?3Hz (corresponding to ?6ppm) were recorded in vitro (2mL in a syringe) and in vivo (over a mouse torso). Comparison of the full width at half maximum (FWHM) for 13C NMR spectra acquired at 48.7mT and at 4.7T in a small-animal MRI scanner demonstrates a factor of ?12 improvement for the 13C resonance linewidth attainable at 48.7mT compared to that at 4.7T in vitro. 13C hyperpolarized succinate-1-13C resonance linewidths in vivo are at least one order of magnitude narrower at 48.7mT compared to those observed in high-field (?3T) studies employing HP contrast agents. The demonstrated high-resolution 13C in vivo spectroscopy could be useful for high-sensitivity spectroscopic studies involving monitoring HP agent uptake or detecting metabolism using HP contrast agents with sufficiently large 13C chemical shift differences.

SUBMITTER: Coffey AM

PROVIDER: S-EPMC5544012 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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High-resolution hyperpolarized in vivo metabolic 13C spectroscopy at low magnetic field (48.7mT) following murine tail-vein injection.

Coffey Aaron M AM Feldman Matthew A MA Shchepin Roman V RV Barskiy Danila A DA Truong Milton L ML Pham Wellington W Chekmenev Eduard Y EY

Journal of magnetic resonance (San Diego, Calif. : 1997) 20170615

High-resolution 13C NMR spectroscopy of hyperpolarized succinate-1-13C-2,3-d2 is reported in vitro and in vivo using a clinical-scale, biplanar (80cm-gap) 48.7mT permanent magnet with a high homogeneity magnetic field. Non-localized 13C NMR spectra were recorded at 0.52MHz resonance frequency over the torso of a tumor-bearing mouse every 2s. Hyperpolarized 13C NMR signals with linewidths of ∼3Hz (corresponding to ∼6ppm) were recorded in vitr ...[more]

PMID: 28651245

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Project description:IntroductionThe normal heart has remarkable metabolic flexibility that permits rapid switching between mitochondrial glucose oxidation and fatty acid (FA) oxidation to generate ATP. Loss of metabolic flexibility has been implicated in the genesis of contractile dysfunction seen in cardiomyopathy. Metabolic flexibility has been imaged in experimental models, using hyperpolarized (HP) [2-13C]pyruvate MRI, which enables interrogation of metabolites that reflect tricarboxylic acid (TCA) cycle flux in cardiac myocytes. This study aimed to develop methods, demonstrate feasibility for [2-13C]pyruvate MRI in the human heart for the first time, and assess cardiac metabolic flexibility.MethodsGood Manufacturing Practice [2-13C]pyruvic acid was polarized in a 5T polarizer for 2.5-3 hours. Following dissolution, QC parameters of HP pyruvate met all safety and sterility criteria for pharmacy release, prior to administration to study subjects. Three healthy subjects each received two HP injections and MR scans, first under fasting conditions, followed by oral glucose load. A 5cm axial slab-selective spectroscopy approach was prescribed over the left ventricle and acquired at 3s intervals on a 3T clinical MRI scanner.ResultsThe study protocol which included HP substrate injection, MR scanning and oral glucose load, was performed safely without adverse events. Key downstream metabolites of [2-13C]pyruvate metabolism in cardiac myocytes include the glycolytic derivative [2-13C]lactate, TCA-associated metabolite [5-13C]glutamate, and [1-13C]acetylcarnitine, catalyzed by carnitine acetyltransferase (CAT). After glucose load, 13C-labeling of lactate, glutamate, and acetylcarnitine from 13C-pyruvate increased by 39.3%, 29.5%, and 114%, respectively in the three subjects, that could result from increases in lactate dehydrogenase (LDH), pyruvate dehydrogenase (PDH), and CAT enzyme activity as well as TCA cycle flux (glucose oxidation).ConclusionsHP [2-13C]pyruvate imaging is safe and permits non-invasive assessment of TCA cycle intermediates and the acetyl buffer, acetylcarnitine, which is not possible using HP [1-13C]pyruvate. Cardiac metabolite measurement in the fasting/fed states provides information on cardiac metabolic flexibility and the acetylcarnitine pool.

Dataset Information

High-resolution hyperpolarized in vivo metabolic 13C spectroscopy at low magnetic field (48.7mT) following murine tail-vein injection.

Publications

High-resolution hyperpolarized in vivo metabolic <sup>13</sup>C spectroscopy at low magnetic field (48.7mT) following murine tail-vein injection.

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