In vivo measurement of ethanol metabolism in the rat liver using magnetic resonance spectroscopy of hyperpolarized [1-13C]pyruvate
β Scribed by Daniel M. Spielman; Dirk Mayer; Yi-Fen Yen; James Tropp; Ralph E. Hurd; Adolf Pfefferbaum
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 574 KB
- Volume
- 62
- Category
- Article
- ISSN
- 0740-3194
No coin nor oath required. For personal study only.
β¦ Synopsis
Abstract
[1β^13^C]Pyruvate is a readily polarizable substrate that has been the subject of numerous magnetic resonance spectroscopy (MRS) studies of in vivo metabolism. In this work ^13^CβMRS of hyperpolarized [1β^13^C]pyruvate was used to interrogate a metabolic pathway involved in neither aerobic nor anaerobic metabolism. In particular, ethanol consumption leads to altered liver metabolism, which when excessive is associated with adverse medical conditions including fatty liver disease, hepatitis, cirrhosis, and cancer. Here we present a method for noninvasively monitoring this important process in vivo. Following the bolus injection of hyperpolarized [1β^13^C]pyruvate, we demonstrate a significantly increased rat liver lactate production rate with the coadministration of ethanol (P = 0.0016 unpaired tβtest). The affect is attributable to increased liver nicotinamide adenine dinucleotide (NADH) associated with ethanol metabolism in combination with NADH's role as a coenzyme in pyruvateβtoβlactate conversion. Beyond studies of liver metabolism, this novel in vivo assay of changes in NADH levels makes hyperpolarized [1β^13^C]pyruvate a potentially viable substrate for studying the multiple in vivo metabolic pathways that use NADH (or NAD^+^) as a coenzyme, thus broadening the range of applications that have been discussed in the literature to date. Magn Reson Med, 2009. Β© 2009 WileyβLiss, Inc.
π SIMILAR VOLUMES
## Abstract Dynamic nuclear polarization can be used to increase the sensitivity of solution state ^13^C magnetic resonance spectroscopy by four orders of magnitude. We show here that [1β^13^C]glutamate can be polarized to 28%, representing a 35,000βfold increase in its sensitivity to detection at
With signalβtoβnoise ratio enhancements on the order of 10,000βfold, hyperpolarized MRSI of metabolically active substrates allows the study of both the injected substrate and downstream metabolic products __in vivo__. Although hyperpolarized [1β^13^C]pyruvate, in particular, has been used to demons
A single-voxel Carr-Purcell-Meibloom-Gill sequence was developed to measure localized T(2) relaxation times of (13)C-labeled metabolites in vivo for the first time. Following hyperpolarized [1-(13)C]pyruvate injections, pyruvate and its metabolic products, alanine and lactate, were observed in the l
We report studies of the effect of ischemia on the metabolic activity of the intact perfused lung and its restoration after a period of reperfusion. Two groups of rat lungs were studied using hyperpolarized 1β^13^C pyruvate to compare the rate of lactate labeling differing only in the temporal order