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 language | English |
|---|---|
| Article number | 19 |
| Journal | Journal of Cardiovascular Magnetic Resonance |
| Volume | 15 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 1 Jan 2013 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - In vivo mouse cardiac hyperpolarized magnetic resonance spectroscopy
AU - Dodd, Michael S.
AU - Ball, Vicky
AU - Bray, Rosalind
AU - Ashrafian, Houman
AU - Watkins, Hugh
AU - Clarke, Kieran
AU - Tyler, Damian J.
PY - 2013/1/1
Y1 - 2013/1/1
N2 - 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.
AB - 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.
KW - Magnetic Resonance Spectroscopy
KW - Mouse Heart
KW - Dynamic Nuclear Polarization
KW - Label Incorporation
KW - Human Heart Disease
UR - http://www.scopus.com/inward/record.url?scp=84873939752&partnerID=8YFLogxK
U2 - 10.1186/1532-429X-15-19
DO - 10.1186/1532-429X-15-19
M3 - Article
VL - 15
JO - Journal of Cardiovascular Magnetic Resonance
JF - Journal of Cardiovascular Magnetic Resonance
SN - 1097-6647
IS - 1
M1 - 19
ER -