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Journal of Cardiovascular Magnetic Resonance
Published in: Journal of Cardiovascular Magnetic Resonance 1/2013

Open Access 01-12-2013 | Research

In vivo mouse cardiac hyperpolarized magnetic resonance spectroscopy

Authors: Michael S Dodd, Vicky Ball, Rosalind Bray, Houman Ashrafian, Hugh Watkins, Kieran Clarke, Damian J Tyler

Published in: Journal of Cardiovascular Magnetic Resonance | Issue 1/2013

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Abstract

Background

Alterations in cardiac metabolism accompany many diseases of the heart. The advent of cardiac hyperpolarized magnetic resonance spectroscopy (MRS), via dynamic nuclear polarization (DNP), has enabled a greater understanding of the in vivo metabolic changes that occur as a consequence of myocardial infarction, hypertrophy and diabetes. However, all cardiac studies performed to date have focused on rats and larger animals, whereas more information could be gained through the study of transgenic mouse models of heart disease. Translation from the rat to the mouse is challenging, due in part to the reduced heart size (1/10th) and the increased heart rate (50%) in the mouse compared to the rat.

Methods and Results

In this study, we have investigated the in vivo metabolism of [1-13C]pyruvate in the mouse heart. To demonstrate the sensitivity of the method to detect alterations in pyruvate dehydrogenase (PDH) flux, two well characterised methods of PDH modulation were performed; overnight fasting and infusion of sodium dichloroacetate (DCA). Fasting resulted in an 85% reduction in PDH flux, whilst DCA infusion increased PDH flux by 123%. A comparison of three commonly used control mouse strains was performed revealing significant metabolic differences between strains.

Conclusions

We have successfully demonstrated a hyperpolarized DNP protocol to investigate in vivo alterations within the diseased mouse heart. This technique offers a significant advantage over existing in vitro techniques as it reduces animal numbers and decreases biological variability. Thus [1-13C]pyruvate can be used to provide an in vivo cardiac metabolic profile of transgenic mice.
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Metadata
Title
In vivo mouse cardiac hyperpolarized magnetic resonance spectroscopy
Authors
Michael S Dodd
Vicky Ball
Rosalind Bray
Houman Ashrafian
Hugh Watkins
Kieran Clarke
Damian J Tyler
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Journal of Cardiovascular Magnetic Resonance / Issue 1/2013
Electronic ISSN: 1532-429X
DOI
https://doi.org/10.1186/1532-429X-15-19

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