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Monitoring acute metabolic changes in the liver and kidneys induced by fructose and glucose using hyperpolarized [2-13 C]dihydroxyacetone.

ABSTRACT: To investigate acute changes in glucose metabolism in liver and kidneys in vivo after a bolus injection of either fructose or glucose, using hyperpolarized [2-13 C]dihydroxyacetone.Spatially registered, dynamic, multislice MR spectroscopy was acquired for the metabolic products of [2-13 C]dihydroxyacetone in liver and kidneys. Metabolism was probed in 13 fasted rats at three time points: 0, 70, and 140?min. At 60?min, rats were injected intravenously with fructose (n?=?5) or glucose (n?=?4) at 0.8?g/kg to initiate acute response. Controls (n?=?4) did not receive a carbohydrate challenge.Ten minutes after fructose infusion, levels of [2-13 C]phosphoenolpyruvate and [2-13 C]glycerol-3-phosphate halved in liver: 51% (P?=?0.0010) and 47% (P?=?0.0001) of baseline, respectively. Seventy minutes later, levels returned to baseline. The glucose challenge did not alter the signals significantly, nor did repeated administration of the dihydroxyacetone imaging bolus. In kidneys, no statistically significant changes were detected after sugar infusion other than a 20% increase of the glycerol-3-phosphate signal between 10 and 80?min after fructose injection (P?=?0.0028).Hyperpolarized [2-13 C]dihydroxyacetone detects a real-time, transient metabolic response of the liver to an acute fructose challenge. Observed effects possibly include ATP depletion and changes in the unlabeled pool sizes of glycolytic intermediates. Magn Reson Med 77:65-73, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

SUBMITTER: Marco-Rius I

PROVIDER: S-EPMC5191913 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Monitoring acute metabolic changes in the liver and kidneys induced by fructose and glucose using hyperpolarized [2-<sup>13</sup> C]dihydroxyacetone.

Marco-Rius Irene I von Morze Cornelius C Sriram Renuka R Cao Peng P Chang Gene-Yuan GY Milshteyn Eugene E Bok Robert A RA Ohliger Michael A MA Pearce David D Kurhanewicz John J Larson Peder E Z PE Vigneron Daniel B DB Merritt Matthew M

Magnetic resonance in medicine 20161117 1

<h4>Purpose</h4>To investigate acute changes in glucose metabolism in liver and kidneys in vivo after a bolus injection of either fructose or glucose, using hyperpolarized [2-<sup>13</sup> C]dihydroxyacetone.<h4>Methods</h4>Spatially registered, dynamic, multislice MR spectroscopy was acquired for the metabolic products of [2-<sup>13</sup> C]dihydroxyacetone in liver and kidneys. Metabolism was probed in 13 fasted rats at three time points: 0, 70, and 140 min. At 60 min, rats were injected intra ...[more]

PMID: 27859575

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Project description:BackgroundHyperpolarized carbon-13 (HP-13C) MRI is a non-invasive imaging technique for probing brain metabolism, which may improve clinical cancer surveillance. This work aimed to characterize the consistency of serial HP-13C imaging in patients undergoing treatment for brain tumors and determine whether there is evidence of aberrant metabolism in the tumor lesion compared to normal-appearing tissue.MethodsSerial dynamic HP [1-13C]pyruvate MRI was performed on 3 healthy volunteers (6 total examinations) and 5 patients (21 total examinations) with diffuse infiltrating glioma during their course of treatment, using a frequency-selective echo-planar imaging (EPI) sequence. HP-13C imaging at routine clinical timepoints overlapped treatment, including radiotherapy (RT), temozolomide (TMZ) chemotherapy, and anti-angiogenic/investigational agents. Apparent rate constants for [1-13C]pyruvate conversion to [1-13C]lactate (kPL) and [13C]bicarbonate (kPB) were simultaneously quantified based on an inputless kinetic model within normal-appearing white matter (NAWM) and anatomic lesions defined from 1H MRI. The inter/intra-subject consistency of kPL-NAWM and kPB-NAWM was measured in terms of the coefficient of variation (CV).ResultsWhen excluding scans following anti-angiogenic therapy, patient values of kPL-NAWM and kPB-NAWM were 0.020 s-1 ± 23.8% and 0.0058 s-1 ± 27.7% (mean ± CV) across 17 HP-13C MRIs, with intra-patient serial kPL-NAWM/kPB-NAWM CVs ranging 6.8-16.6%/10.6-40.7%. In 4/5 patients, these values (0.018 s-1 ± 13.4% and 0.0058 s-1 ± 24.4%; n = 13) were more similar to those from healthy volunteers (0.018 s-1 ± 5.0% and 0.0043 s-1 ± 12.6%; n = 6) (mean ± CV). The anti-angiogenic agent bevacizumab was associated with global elevations in apparent rate constants, with maximum kPL-NAWM in 2 patients reaching 0.047 ± 0.001 and 0.047 ± 0.003 s-1 (±model error). In 3 patients with progressive disease, anatomic lesions showed elevated kPL relative to kPL-NAWM of 0.024 ± 0.001 s-1 (±model error) in the absence of gadolinium enhancement, and 0.032 ± 0.008, 0.040 ± 0.003 and 0.041 ± 0.009 s-1 with gadolinium enhancement. The lesion kPB in patients was reduced to unquantifiable values compared to kPB-NAWM.ConclusionSerial measures of HP [1-13C]pyruvate metabolism displayed consistency in the NAWM of healthy volunteers and patients. Both kPL and kPB were globally elevated following bevacizumab treatment, while progressive disease demonstrated elevated kPL in gadolinium-enhancing and non-enhancing lesions. Larger prospective studies with homogeneous patient populations are planned to evaluate metabolic changes following treatment.

Dataset Information

Monitoring acute metabolic changes in the liver and kidneys induced by fructose and glucose using hyperpolarized [2-13 C]dihydroxyacetone.

Publications

Monitoring acute metabolic changes in the liver and kidneys induced by fructose and glucose using hyperpolarized [2-<sup>13</sup> C]dihydroxyacetone.

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