In vivo mouse cardiac hyperpolarized magnetic resonance spectroscopy

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

Research output: Contribution to journalArticle

25 Citations (Scopus)

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.

Original languageEnglish
Article number19
JournalJournal of Cardiovascular Magnetic Resonance
Volume15
Issue number1
DOIs
Publication statusPublished - 1 Jan 2013
Externally publishedYes

Fingerprint

Pyruvic Acid
Magnetic Resonance Spectroscopy
Oxidoreductases
Heart Diseases
Transgenic Mice
Fasting
Dichloroacetic Acid
Metabolome
Hypertrophy
Heart Rate
Myocardial Infarction

Keywords

  • Magnetic Resonance Spectroscopy
  • Mouse Heart
  • Dynamic Nuclear Polarization
  • Label Incorporation
  • Human Heart Disease

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

Cite this

In vivo mouse cardiac hyperpolarized magnetic resonance spectroscopy. / Dodd, Michael S.; Ball, Vicky; Bray, Rosalind; Ashrafian, Houman; Watkins, Hugh; Clarke, Kieran; Tyler, Damian J.

In: Journal of Cardiovascular Magnetic Resonance, Vol. 15, No. 1, 19, 01.01.2013.

Research output: Contribution to journalArticle

Dodd, Michael S. ; Ball, Vicky ; Bray, Rosalind ; Ashrafian, Houman ; Watkins, Hugh ; Clarke, Kieran ; Tyler, Damian J. / In vivo mouse cardiac hyperpolarized magnetic resonance spectroscopy. In: Journal of Cardiovascular Magnetic Resonance. 2013 ; Vol. 15, No. 1.
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