Dataset Information

Evaluation of Active Brown Adipose Tissue by the Use of Hyperpolarized [1-¹³C]Pyruvate MRI in Mice.

ABSTRACT: The capacity to increase energy expenditure makes brown adipose tissue (BAT) a putative target for treatment of metabolic diseases such as obesity. Presently, investigation of BAT in vivo is mainly performed by fluoro-d-glucose positron emission tomography (FDG PET)/CT. However, non-radioactive methods that add information on, for example, substrate metabolism are warranted. Thus, the aim of this study was to evaluate the potential of hyperpolarized [1-¹³C]pyruvate Magnetic Resonance Imaging (HP-MRI) to determine BAT activity in mice following chronic cold exposure. Cold (6 °C) and thermo-neutral (30 °C) acclimated mice were scanned with HP-MRI for assessment of the interscapular BAT (iBAT) activity. Comparable mice were scanned with the conventional method FDG PET/MRI. Finally, iBAT was evaluated for gene expression and protein levels of the specific thermogenic marker, uncoupling protein 1 (UCP1). Cold exposure increased the thermogenic capacity 3?4 fold (p < 0.05) as measured by UCP1 gene and protein analysis. Furthermore, cold exposure as compared with thermo-neutrality increased iBAT pyruvate metabolism by 5.5-fold determined by HP-MRI which is in good agreement with the 5-fold increment in FDG uptake (p < 0.05) measured by FDG PET/MRI. iBAT activity is detectable in mice using HP-MRI in which potential changes in intracellular metabolism may add useful information to the conventional FDG PET studies. HP-MRI may also be a promising radiation-free tool for repetitive BAT studies in humans.

SUBMITTER: Riis-Vestergaard MJ

PROVIDER: S-EPMC6164296 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Evaluation of Active Brown Adipose Tissue by the Use of Hyperpolarized [1-<sup>13</sup>C]Pyruvate MRI in Mice.

Riis-Vestergaard Mette Ji MJ Breining Peter P Pedersen Steen Bønløkke SB Laustsen Christoffer C Stødkilde-Jørgensen Hans H Borghammer Per P Jessen Niels N Richelsen Bjørn B Richelsen Bjørn B

International journal of molecular sciences 20180901 9

The capacity to increase energy expenditure makes brown adipose tissue (BAT) a putative target for treatment of metabolic diseases such as obesity. Presently, investigation of BAT in vivo is mainly performed by fluoro-d-glucose positron emission tomography (FDG PET)/CT. However, non-radioactive methods that add information on, for example, substrate metabolism are warranted. Thus, the aim of this study was to evaluate the potential of hyperpolarized [1-<sup>13</sup>C]pyruvate Magnetic Resonance ...[more]

PMID: 30200469

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Project description:MRI using hyperpolarized (HP) carbon-13 pyruvate is being investigated in clinical trials to provide non-invasive measurements of metabolism for cancer and cardiac imaging. In this project, we applied HP [1-13 C]pyruvate dynamic MRI in prostate cancer to measure the conversion from pyruvate to lactate, which is expected to increase in aggressive cancers. The goal of this work was to develop and test analysis methods for improved quantification of this metabolic conversion. In this work, we compared specialized kinetic modeling methods to estimate the pyruvate-to-lactate conversion rate, kPL , as well as the lactate-to-pyruvate area-under-curve (AUC) ratio. The kinetic modeling included an "inputless" method requiring no assumptions regarding the input function, as well as a method incorporating bolus characteristics in the fitting. These were first evaluated with simulated data designed to match human prostate data, where we examined the expected sensitivity of metabolism quantification to variations in kPL , signal-to-noise ratio (SNR), bolus characteristics, relaxation rates, and B1 variability. They were then applied to 17 prostate cancer patient datasets. The simulations indicated that the inputless method with fixed relaxation rates provided high expected accuracy with no sensitivity to bolus characteristics. The AUC ratio showed an undesired strong sensitivity to bolus variations. Fitting the input function as well did not improve accuracy over the inputless method. In vivo results showed qualitatively accurate kPL maps with inputless fitting. The AUC ratio was sensitive to bolus delivery variations. Fitting with the input function showed high variability in parameter maps. Overall, we found the inputless kPL fitting method to be a simple, robust approach for quantification of metabolic conversion following HP [1-13 C]pyruvate injection in human prostate cancer studies. This study also provided initial ranges of HP [1-13 C]pyruvate parameters (SNR, kPL , bolus characteristics) in the human prostate.

Dataset Information

Evaluation of Active Brown Adipose Tissue by the Use of Hyperpolarized [1-¹³C]Pyruvate MRI in Mice.

Publications

Evaluation of Active Brown Adipose Tissue by the Use of Hyperpolarized [1-<sup>13</sup>C]Pyruvate MRI in Mice.

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Dataset Information

Evaluation of Active Brown Adipose Tissue by the Use of Hyperpolarized [1-13C]Pyruvate MRI in Mice.

Publications

Evaluation of Active Brown Adipose Tissue by the Use of Hyperpolarized [1-<sup>13</sup>C]Pyruvate MRI in Mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Evaluation of Active Brown Adipose Tissue by the Use of Hyperpolarized [1-¹³C]Pyruvate MRI in Mice.