Dataset Information

Enhancing Metabolic Imaging of Energy Metabolism in Traumatic Brain Injury Using Hyperpolarized [1-13C]Pyruvate and Dichloroacetate.

ABSTRACT: Hyperpolarized magnetic resonance spectroscopic imaging (MRSI) of [1-13C]pyruvate metabolism has previously been used to assess the effects of traumatic brain injury (TBI) in rats. Here, we show that MRSI can be used in conjunction with dichloroacetate to measure the phosphorylation state of pyruvate dehydrogenase (PDH) following mild-to-moderate TBI, and that measurements can be repeated in a longitudinal study to monitor the course of injury progression and recovery. We found that the level of 13C-bicarbonate and the bicarbonate-to-lactate ratio decreased on the injured side of the brain four hours after injury and continued to decrease through day 7. Levels recovered to normal by day 28. Measurements following dichloroacetate administration showed that PDH was inhibited equally by PDH kinase (PDK) on both sides of the brain. Therefore, the decrease in aerobic metabolism is not due to inhibition by PDK.

SUBMITTER: DeVience SJ

PROVIDER: S-EPMC8225170 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Enhancing Metabolic Imaging of Energy Metabolism in Traumatic Brain Injury Using Hyperpolarized [1-<sup>13</sup>C]Pyruvate and Dichloroacetate.

DeVience Stephen J SJ Lu Xin X Proctor Julie L JL Rangghran Parisa P Medina Juliana A JA Melhem Elias R ER Gullapalli Rao P RP Fiskum Gary G Mayer Dirk D

Metabolites 20210524 6

Hyperpolarized magnetic resonance spectroscopic imaging (MRSI) of [1-<sup>13</sup>C]pyruvate metabolism has previously been used to assess the effects of traumatic brain injury (TBI) in rats. Here, we show that MRSI can be used in conjunction with dichloroacetate to measure the phosphorylation state of pyruvate dehydrogenase (PDH) following mild-to-moderate TBI, and that measurements can be repeated in a longitudinal study to monitor the course of injury progression and recovery. We found that t ...[more]

PMID: 34073714

Similar Datasets

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

Enhancing Metabolic Imaging of Energy Metabolism in Traumatic Brain Injury Using Hyperpolarized [1-13C]Pyruvate and Dichloroacetate.

Publications

Enhancing Metabolic Imaging of Energy Metabolism in Traumatic Brain Injury Using Hyperpolarized [1-<sup>13</sup>C]Pyruvate and Dichloroacetate.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets