Advertisement

Imaging Myocardial Metabolism

  • Robert J. GroplerEmail author
  • Craig R. Malloy
Chapter

Abstract

Metabolism of exogenous and endogenous substrates, under baseline conditions and in response to metabolic and physiological stimuli, is central to cardiac myocyte health. The ever-burgeoning body of evidence demonstrating the primacy of perturbations in intermediary metabolism in the pathogenesis of common cardiovascular diseases such as ischemic heart disease, heart failure, and diabetic cardiomyopathy further supports this contention. It is becoming increasingly apparent that chronic adaptations in cellular metabolism initiates a host of pleiotropic actions detrimental to cellular health such as impaired energetics, increases in inflammation, oxidative stress, and apoptosis [1, 2]. Our understanding of metabolic pathways continues to evolve with the acquisition of vast quantities of information from metabolomics, proteomics, and transcriptomics that are integrated from “big-data” sets such as the Kyoto Encyclopedia of Genes and Genomes [3]. The importance of myocardial metabolism was highlighted in a recent scientific statement from the American Heart Association [4]. Finally, interest in modifying intermediary metabolism underlying human cardiovascular disease is exemplified by the robust drug discovery and development efforts to identify new metabolic modulators [5].

Abbreviations

ATP

Adenosine triphosphate

DNP

Dynamic nuclear polarization

HP

Hyperpolarization

LV

Left ventricle

MRI

Magnetic resonance imaging

MRS

Magnetic resonance spectroscopy

PDH

Pyruvate dehydrogenase

PET

Positron emission computed tomography

PPP

Pentose phosphate pathway

RV

Right ventricle

SPECT

Single photon emission computed tomography

TCA

Tricarboxylic acid

TG

Triglycerides

References

  1. 1.
    Ardenkjaer-Larsen JH, et al. Increase in signal-to-noise ratio of > 10,000 times in liquid-state NMR. Proc Natl Acad Sci U S A. 2003;100(18):10158–63.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Golman K, et al. Molecular imaging with endogenous substances. Proc Natl Acad Sci U S A. 2003;100(18):10435–9.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Nelson SJ, et al. Metabolic imaging of patients with prostate cancer using hyperpolarized [1-(1)(3)C]pyruvate. Sci Transl Med. 2013; 5(198): 198ra108.Google Scholar
  4. 4.
    Taegtmeyer H. Six blind men explore an elephant: aspects of fuel metabolism and the control of tricarboxylic acid cycle activity in heart muscle. Basic Res Cardiol. 1984;79(3):322–36.PubMedCrossRefGoogle Scholar
  5. 5.
    Moreno KX, et al. Competition of pyruvate with physiological substrates for oxidation by the heart: implications for studies with hyperpolarized [1-13C]pyruvate. Am J Physiol Heart Circ Physiol. 2010;298(5):H1556–64.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Jeffrey FM, et al. Substrate selection in the isolated working rat heart: effects of reperfusion, afterload, and concentration. Basic Res Cardiol. 1995;90(5):388–96.PubMedCrossRefGoogle Scholar
  7. 7.
    Jeffrey FM, et al. Direct evidence that perhexiline modifies myocardial substrate utilization from fatty acids to lactate. J Cardiovasc Pharmacol. 1995;25(3):469–72.PubMedCrossRefGoogle Scholar
  8. 8.
    Drake AJ, Haines JR, Noble MI. Preferential uptake of lactate by the normal myocardium in dogs. Cardiovasc Res. 1980;14(2):65–72.PubMedCrossRefGoogle Scholar
  9. 9.
    Banke NH, et al. Preferential oxidation of triacylglyceride-derived fatty acids in heart is augmented by the nuclear receptor PPARalpha. Circ Res. 2010;107(2):233–41.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Saddik M, Lopaschuk GD. Myocardial triglyceride turnover and contribution to energy substrate utilization in isolated working rat hearts. J Biol Chem. 1991;266(13):8162–70.PubMedGoogle Scholar
  11. 11.
    Armbrecht JJ, Buxton DB, Schelbert HR. Validation of [1-11C]acetate as a tracer for noninvasive assessment of oxidative metabolism with positron emission tomography in normal, ischemic, postischemic, and hyperemic canine myocardium. Circulation. 1990;81(5):1594–605.PubMedCrossRefGoogle Scholar
  12. 12.
    Abbas AS, Wu G, Schulz H. Carnitine acetyltransferase is not a cytosolic enzyme in rat heart and therefore cannot function in the energy-linked regulation of cardiac fatty acid oxidation. J Mol Cell Cardiol. 1998;30(7):1305–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Bakker A, et al. Ultrastructural localisation of carnitine acetyltransferase activity in mitochondria of rat myocardium. Biochim Biophys Acta. 1994;1185(1):97–102.PubMedCrossRefGoogle Scholar
  14. 14.
    Remesy C, Demigne C. Changes in availability of glucogenic and ketogenic substrates and liver metabolism in fed or starved rats. Ann Nutr Metab. 1983;27(1):57–70.PubMedCrossRefGoogle Scholar
  15. 15.
    Owen OE, et al. Liver and kidney metabolism during prolonged starvation. J Clin Invest. 1969;48(3):574–83.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Hansford RG, Cohen L. Relative importance of pyruvate dehydrogenase interconversion and feed-back inhibition in the effect of fatty acids on pyruvate oxidation by rat heart mitochondria. Arch Biochem Biophys. 1978;191(1):65–81.PubMedCrossRefGoogle Scholar
  17. 17.
    Latipaa PM, et al. Regulation of pyruvate dehydrogenase during infusion of fatty acids of varying chain lengths in the perfused rat heart. J Mol Cell Cardiol. 1985;17(12):1161–71.PubMedCrossRefGoogle Scholar
  18. 18.
    Purmal C, et al. Propionate stimulates pyruvate oxidation in the presence of acetate. Am J Physiol Heart Circ Physiol. 2014;307(8):H1134–41.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Bunger R. Compartmented pyruvate in perfused working heart. Am J Phys. 1985;249(3 Pt 2):H439–49.Google Scholar
  20. 20.
    Malloy CR, Sherry AD, Jeffrey FM. Evaluation of carbon flux and substrate selection through alternate pathways involving the citric acid cycle of the heart by 13C NMR spectroscopy. J Biol Chem. 1988;263(15):6964–71.PubMedGoogle Scholar
  21. 21.
    Peuhkurinen KJ, et al. Role of pyruvate carboxylation in the energy-linked regulation of pool sizes of tricarboxylic acid-cycle intermediates in the myocardium. Biochem J. 1982;208(3):577–81.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Depre C, Vanoverschelde JL, Taegtmeyer H. Glucose for the heart. Circulation. 1999;99(4):578–88.PubMedCrossRefGoogle Scholar
  23. 23.
    Zimmer HG. Regulation of and intervention into the oxidative pentose phosphate pathway and adenine nucleotide metabolism in the heart. Mol Cell Biochem. 1996;160-161:101–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Zimmer HG. The oxidative pentose phosphate pathway in the heart: regulation, physiological significance, and clinical implications. Basic Res Cardiol. 1992;87(4):303–16.PubMedCrossRefGoogle Scholar
  25. 25.
    Vimercati C, et al. Beneficial effects of acute inhibition of the oxidative pentose phosphate pathway in the failing heart. Am J Physiol Heart Circ Physiol. 2014;306(5):H709–17.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Nuutinen EM, et al. Elimination and replenishment of tricarboxylic acid-cycle intermediates in myocardium. Biochem J. 1981;194(3):867–75.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Peuhkurinen KJ, Hiltunen JK, Hassinen IE. Metabolic compartmentation of pyruvate in the isolated perfused rat heart. Biochem J. 1983;210(1):193–8.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Peuhkurinen KJ, Hassinen IE. Pyruvate carboxylation as an anaplerotic mechanism in the isolated perfused rat heart. Biochem J. 1982;202(1):67–76.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Sherry AD, et al. Propionate metabolism in the rat heart by 13C n.M.R. Spectroscopy. Biochem J. 1988;254(2):593–8.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Chatham JC, Forder JR. Metabolic compartmentation of lactate in the glucose-perfused rat heart. Am J Phys. 1996;270(1 Pt 2):H224–9.Google Scholar
  31. 31.
    Mowbray J, Ottaway JH. The flux of pyruvate in perfused rat heart. Eur J Biochem. 1973;36(2):362–8.PubMedCrossRefGoogle Scholar
  32. 32.
    Mowbray J, Ottaway JH. The effect of insulin and growth hormone on the flux of tracer from labelled lactate in perfused rat heart. Eur J Biochem. 1973;36(2):369–79.PubMedCrossRefGoogle Scholar
  33. 33.
    Li Q, et al. Multiple mass isotopomer tracing of acetyl-CoA metabolism in Langendorff-perfused rat hearts: channeling of acetyl-CoA from pyruvate dehydrogenase to carnitine acetyltransferase. J Biol Chem. 2015;290(13):8121–32.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Anousis N, et al. Compartmentation of glycolysis and glycogenolysis in the perfused rat heart. NMR Biomed. 2004;17(2):51–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Khemtong C, et al. Hyperpolarized 13C NMR detects rapid drug-induced changes in cardiac metabolism. Magn Reson Med. 2015;74(2):312–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Schinkel AF, et al. Hibernating myocardium: diagnosis and patient outcomes. Curr Probl Cardiol. 2007;32(7):375–410.PubMedCrossRefGoogle Scholar
  37. 37.
    DeGrado TR, et al. Quantitative analysis of myocardial kinetics of 15-p-[iodine-125] iodophenylpentadecanoic acid. J Nucl Med. 1989;30(7):1211–8.PubMedGoogle Scholar
  38. 38.
    Dormehl IC, et al. Planar myocardial imaging in the baboon model with iodine-123-15-(iodophenyl)pentadecanoic acid (IPPA) and iodine-123-15-(P-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP), using time-activity curves for evaluation of metabolism. Nucl Med Biol. 1995;22(7):837–47.PubMedCrossRefGoogle Scholar
  39. 39.
    Eckelman WC, Babich JW. Synthesis and validation of fatty acid analogs radiolabeled by nonisotopic substitution. J Nucl Cardiol. 2007;14(3 Suppl):S100–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Ambrose KR, et al. Evaluation of the metabolism in rat hearts of two new radioiodinated 3-methyl-branched fatty acid myocardial imaging agents. Eur J Nucl Med. 1987;12(10):486–91.PubMedCrossRefGoogle Scholar
  41. 41.
    Goodman MM, Kirsch G, Knapp FF Jr. Synthesis and evaluation of radioiodinated terminal p-iodophenyl-substituted alpha- and beta-methyl-branched fatty acids. J Med Chem. 1984;27(3):390–7.PubMedCrossRefGoogle Scholar
  42. 42.
    Reske SN, et al. Metabolism of 15 (p 123I iodophenyl-)pentadecanoic acid in heart muscle and noncardiac tissues. Eur J Nucl Med. 1985;10(5-6):228–34.PubMedGoogle Scholar
  43. 43.
    He ZX, et al. Direct imaging of exercise-induced myocardial ischemia with fluorine-18-labeled deoxyglucose and Tc-99m-sestamibi in coronary artery disease. Circulation. 2003;108(10):1208–13.PubMedCrossRefGoogle Scholar
  44. 44.
    Iida H, et al. Noninvasive quantification of regional myocardial metabolic rate for oxygen by use of 15O2 inhalation and positron emission tomography. Theory, error analysis, and application in humans. Circulation. 1996;94(4):792–807.PubMedCrossRefGoogle Scholar
  45. 45.
    Laine H, et al. Myocardial oxygen consumption is unchanged but efficiency is reduced in patients with essential hypertension and left ventricular hypertrophy. Circulation. 1999;100(24):2425–30.PubMedCrossRefGoogle Scholar
  46. 46.
    Yamamoto Y, et al. Noninvasive quantification of regional myocardial metabolic rate of oxygen by 15O2 inhalation and positron emission tomography, experimental validation. Circulation. 1996;94(4):808–16.PubMedCrossRefGoogle Scholar
  47. 47.
    Brown M, et al. Delineation of myocardial oxygen utilization with carbon-11-labeled acetate. Circulation. 1987;76(3):687–96.PubMedCrossRefGoogle Scholar
  48. 48.
    Brown MA, Myears DW, Bergmann SR. Noninvasive assessment of canine myocardial oxidative metabolism with carbon-11 acetate and positron emission tomography. J Am Coll Cardiol. 1988;12(4):1054–63.PubMedCrossRefGoogle Scholar
  49. 49.
    Buck A, et al. Effect of carbon-11-acetate recirculation on estimates of myocardial oxygen consumption by PET. J Nucl Med. 1991;32(10):1950–7.PubMedGoogle Scholar
  50. 50.
    Sun KT, et al. Simultaneous measurement of myocardial oxygen consumption and blood flow using [1-carbon-11]acetate. J Nucl Med. 1998;39(2):272–80.PubMedGoogle Scholar
  51. 51.
    Choi Y, et al. Parametric images of myocardial metabolic rate of glucose generated from dynamic cardiac PET and 2-[18F]fluoro-2-deoxy-d-glucose studies. J Nucl Med. 1991;32(4):733–8.PubMedGoogle Scholar
  52. 52.
    Gambert S, et al. Adverse effects of free fatty acid associated with increased oxidative stress in postischemic isolated rat hearts. Mol Cell Biochem. 2006;283(1-2):147–52.PubMedCrossRefGoogle Scholar
  53. 53.
    Iozzo P, et al. Regional myocardial blood flow and glucose utilization during fasting and physiological hyperinsulinemia in humans. Am J Physiol Endocrinol Metab. 2002;282(5):E1163–71.PubMedCrossRefGoogle Scholar
  54. 54.
    Krivokapich J, et al. Fluorodeoxyglucose rate constants, lumped constant, and glucose metabolic rate in rabbit heart. Am J Phys. 1987;252(4 Pt 2):H777–87.Google Scholar
  55. 55.
    Botker HE, et al. Glucose uptake and lumped constant variability in normal human hearts determined with [18F]fluorodeoxyglucose. J Nucl Cardiol. 1997;4(2 Pt 1):125–32.PubMedCrossRefGoogle Scholar
  56. 56.
    Hariharan R, et al. Fundamental limitations of [18F]2-deoxy-2-fluoro-D-glucose for assessing myocardial glucose uptake. Circulation. 1995;91(9):2435–44.PubMedCrossRefGoogle Scholar
  57. 57.
    Hashimoto K, et al. Lumped constant for deoxyglucose is decreased when myocardial glucose uptake is enhanced. Am J Phys. 1999;276(1 Pt 2):H129–33.Google Scholar
  58. 58.
    Herrero P, et al. L-3-11C-lactate as a PET tracer of myocardial lactate metabolism: a feasibility study. J Nucl Med. 2007;48(12):2046–55.PubMedCrossRefGoogle Scholar
  59. 59.
    Bergmann SR, et al. Quantitation of myocardial fatty acid metabolism using PET. J Nucl Med. 1996;37(10):1723–30.PubMedGoogle Scholar
  60. 60.
    Herrero P, et al. Increased myocardial fatty acid metabolism in patients with type 1 diabetes mellitus. J Am Coll Cardiol. 2006;47(3):598–604.PubMedCrossRefGoogle Scholar
  61. 61.
    Kisrieva-Ware Z, et al. Assessment of myocardial triglyceride oxidation with PET and 11C-palmitate. J Nucl Cardiol.Google Scholar
  62. 62.
    DeGrado TR. Synthesis of 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid (FTHA). J Label Comp Radiopharm. 1991;29:989–95.CrossRefGoogle Scholar
  63. 63.
    DeGrado TR, Coenen HH, Stocklin G. 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid (FTHA): evaluation in mouse of a new probe of myocardial utilization of long chain fatty acids. J Nucl Med. 1991;32(10):1888–96.PubMedGoogle Scholar
  64. 64.
    DeGrado TR, et al. Synthesis and preliminary evaluation of (18)F-labeled 4-thia palmitate as a PET tracer of myocardial fatty acid oxidation. Nucl Med Biol. 2000;27(3):221–31.PubMedCrossRefGoogle Scholar
  65. 65.
    DeGrado TR, et al. Validation of 18F-fluoro-4-thia-palmitate as a PET probe for myocardial fatty acid oxidation: effects of hypoxia and composition of exogenous fatty acids. J Nucl Med. 2006;47(1):173–81.PubMedGoogle Scholar
  66. 66.
    DeGrado TR, et al. Synthesis and preliminary evaluation of 18-(18)F-fluoro-4-thia-oleate as a PET probe of fatty acid oxidation. J Nucl Med. 2010;51(8):1310–7.PubMedCrossRefGoogle Scholar
  67. 67.
    Shoup TM, et al. Evaluation of trans-9-18F-fluoro-3,4-Methyleneheptadecanoic acid as a PET tracer for myocardial fatty acid imaging. J Nucl Med. 2005;46(2):297–304.PubMedGoogle Scholar
  68. 68.
    Demeure F, et al. A new F-18 labeled PET tracer for fatty acid imaging. J Nucl Cardiol. 2015;22(2):391–4.PubMedCrossRefGoogle Scholar
  69. 69.
    Labbe SM, et al. Increased myocardial uptake of dietary fatty acids linked to cardiac dysfunction in glucose-intolerant humans. Diabetes. 2012;61(11):2701–10.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Labbe SM, et al. Organ-specific dietary fatty acid uptake in humans using positron emission tomography coupled to computed tomography. Am J Physiol Endocrinol Metab. 2011;300(3):E445–53.PubMedCrossRefGoogle Scholar
  71. 71.
    Shoghi KI, Gropler RJ. PET measurements of organ metabolism: the devil is in the details. Diabetes. 2015;64(7):2332–4.PubMedCrossRefGoogle Scholar
  72. 72.
    O'Donnell JM, et al. The absence of endogenous lipid oxidation in early stage heart failure exposes limits in lipid storage and turnover. J Mol Cell Cardiol. 2008;44(2):315–22.PubMedCrossRefGoogle Scholar
  73. 73.
    Saddik M, Lopaschuk GD. Triacylglycerol turnover in isolated working hearts of acutely diabetic rats. Can J Physiol Pharmacol. 1994;72(10):1110–9.PubMedCrossRefGoogle Scholar
  74. 74.
    Wisneski JA, et al. Myocardial metabolism of free fatty acids. Studies with 14C-labeled substrates in humans. J Clin Invest. 1987;79(2):359–66.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Wicklmayr M, et al. Inhibition of muscular triglyceride lipolysis by ketone bodies: a mechanism for energy-preservation in starvation. Horm Metab Res. 1986;18(7):476–8.PubMedCrossRefGoogle Scholar
  76. 76.
    Kisrieva-Ware Z, et al. Assessment of myocardial triglyceride oxidation with PET and 11C-palmitate. J Nucl Cardiol. 2009;16(3):411–21.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Bucci M, et al. Trimetazidine reduces endogenous free fatty acid oxidation and improves myocardial efficiency in obese humans. Cardiovasc Ther. 2012;30(6):333–41.PubMedCrossRefGoogle Scholar
  78. 78.
    Brindle KM. Imaging metabolism with hyperpolarized (13)C-labeled cell substrates. J Am Chem Soc. 2015;137(20):6418–27.PubMedCrossRefGoogle Scholar
  79. 79.
    Comment A, Merritt ME. Hyperpolarized magnetic resonance as a sensitive detector of metabolic function. Biochemistry. 2014;53(47):7333–57.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Kurhanewicz J, et al. Analysis of cancer metabolism by imaging hyperpolarized nuclei: prospects for translation to clinical research. Neoplasia. 2011;13(2):81–97.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Bhattacharya P, Ross BD, Bunger R. Cardiovascular applications of hyperpolarized contrast media and metabolic tracers. Exp Biol Med (Maywood). 2009;234(12):1395–416.CrossRefGoogle Scholar
  82. 82.
    Tyler DJ. Cardiovascular applications of hyperpolarized MRI. Curr Cardiovasc Imaging Rep. 2011;4(2):108–15.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Rider OJ, Tyler DJ. Clinical implications of cardiac hyperpolarized magnetic resonance imaging. J Cardiovasc Magn Reson. 2013;15:93.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Keshari KR, Wilson DM. Chemistry and biochemistry of 13C hyperpolarized magnetic resonance using dynamic nuclear polarization. Chem Soc Rev. 2014;43(5):1627–59.PubMedCrossRefGoogle Scholar
  85. 85.
    Lau AZ, et al. Simultaneous assessment of cardiac metabolism and perfusion using copolarized [1-13 C]pyruvate and 13 C-urea. Magn Reson Med. 2016.Google Scholar
  86. 86.
    Golman K, Petersson JS. Metabolic imaging and other applications of hyperpolarized 13C1. Acad Radiol. 2006;13(8):932–42.PubMedCrossRefGoogle Scholar
  87. 87.
    Golman K, et al. Cardiac metabolism measured noninvasively by hyperpolarized 13C MRI. Magn Reson Med. 2008;59(5):1005–13.PubMedCrossRefGoogle Scholar
  88. 88.
    Lau AZ, et al. Rapid multislice imaging of hyperpolarized 13C pyruvate and bicarbonate in the heart. Magn Reson Med. 2010;64(5):1323–31.PubMedCrossRefGoogle Scholar
  89. 89.
    Schroeder MA, et al. Hyperpolarized (13)C magnetic resonance reveals early- and late-onset changes to in vivo pyruvate metabolism in the failing heart. Eur J Heart Fail. 2013;15(2):130–40.PubMedCrossRefGoogle Scholar
  90. 90.
    Merritt ME, et al. Hyperpolarized 13C allows a direct measure of flux through a single enzyme-catalyzed step by NMR. Proc Natl Acad Sci U S A. 2007;104(50):19773–7.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Lau, A.Z., J.J. Miller, and D.J. Tyler, Mapping of intracellular pH in the in vivo rodent heart using hyperpolarized [1-13C]pyruvate. Magn Reson Med, 2016.Google Scholar
  92. 92.
    Dominguez-Viqueira W, et al. Intensity correction for multichannel hyperpolarized 13C imaging of the heart. Magn Reson Med. 2016;75(2):859–65.PubMedCrossRefGoogle Scholar
  93. 93.
    Schroeder MA, et al. Real-time assessment of Krebs cycle metabolism using hyperpolarized 13C magnetic resonance spectroscopy. FASEB J. 2009;23(8):2529–38.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Chen AP, et al. Simultaneous investigation of cardiac pyruvate dehydrogenase flux, Krebs cycle metabolism and pH, using hyperpolarized [1,2-(13)C2]pyruvate in vivo. NMR Biomed. 2012;25(2):305–11.PubMedCrossRefGoogle Scholar
  95. 95.
    Chen AP, et al. Using [1-(13) C]lactic acid for hyperpolarized (13) C MR cardiac studies. Magn Reson Med. 2015;73(6):2087–93.PubMedCrossRefGoogle Scholar
  96. 96.
    Jensen PR, et al. Tissue-specific short chain fatty acid metabolism and slow metabolic recovery after ischemia from hyperpolarized NMR in vivo. J Biol Chem. 2009;284(52):36077–82.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Bastiaansen JA, et al. Direct noninvasive estimation of myocardial tricarboxylic acid cycle flux in vivo using hyperpolarized (1)(3)C magnetic resonance. J Mol Cell Cardiol. 2015;87:129–37.PubMedCrossRefGoogle Scholar
  98. 98.
    Flori A, et al. Real-time cardiac metabolism assessed with hyperpolarized [1-(13) C]acetate in a large-animal model. Contrast Media Mol Imaging. 2015;10(3):194–202.PubMedCrossRefGoogle Scholar
  99. 99.
    Ball DR, et al. Hyperpolarized butyrate: a metabolic probe of short chain fatty acid metabolism in the heart. Magn Reson Med. 2014;71(5):1663–9.PubMedCrossRefGoogle Scholar
  100. 100.
    Vary TC, Reibel DK, Neely JR. Control of energy metabolism of heart muscle. Annu Rev Physiol. 1981;43:419–30.PubMedCrossRefGoogle Scholar
  101. 101.
    Neely JR, Morgan HE. Relationship between carbohydrate and lipid metabolism and the energy balance of heart muscle. Annu Rev Physiol. 1974;36:413–59.PubMedCrossRefGoogle Scholar
  102. 102.
    Lopaschuk G. Regulation of carbohydrate metabolism in ischemia and reperfusion. Am Heart J. 2000;139(2 Pt 3):S115–9.PubMedCrossRefGoogle Scholar
  103. 103.
    Araujo LI, et al. Abnormalities in myocardial metabolism in patients with unstable angina as assessed by positron emission tomography. Cardiovasc Drugs Ther. 1988;2(1):41–6.PubMedCrossRefGoogle Scholar
  104. 104.
    Camici P, et al. Increased uptake of 18F-fluorodeoxyglucose in postischemic myocardium of patients with exercise-induced angina. Circulation. 1986;74(1):81–8.PubMedCrossRefGoogle Scholar
  105. 105.
    Tamaki N, et al. The role of fatty acids in cardiac imaging. J Nucl Med. 2000;41(9):1525–34.PubMedGoogle Scholar
  106. 106.
    Kawai Y, et al. Diagnostic value of 123I-betamethyl-p-iodophenyl-pentadecanoic acid (BMIPP) single photon emission computed tomography (SPECT) in patients with chest pain. Comparison with rest-stress 99mTc-tetrofosmin SPECT and coronary angiography. Circ J. 2004;68(6):547–52.PubMedCrossRefGoogle Scholar
  107. 107.
    Kontos MC, et al. Iodofiltic acid I 123 (BMIPP) fatty acid imaging improves initial diagnosis in emergency department patients with suspected acute coronary syndromes: a multicenter trial. J Am Coll Cardiol. 2010;56(4):290–9.PubMedCrossRefGoogle Scholar
  108. 108.
    Moroi M, et al. Association between abnormal myocardial fatty acid metabolism and cardiac-derived death among patients undergoing hemodialysis: results from a cohort study in Japan. Am J Kidney Dis. 2013;61(3):466–75.PubMedCrossRefGoogle Scholar
  109. 109.
    Dou KF, et al. Myocardial 18F-FDG uptake after exercise-induced myocardial ischemia in patients with coronary artery disease. J Nucl Med. 2008;49(12):1986–91.PubMedCrossRefGoogle Scholar
  110. 110.
    Merritt ME, et al. Inhibition of carbohydrate oxidation during the first minute of reperfusion after brief ischemia: NMR detection of hyperpolarized 13CO2 and H13CO3. Magn Reson Med. 2008;60(5):1029–36.PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Rupp H, Jacob R. Metabolically-modulated growth and phenotype of the rat heart. Eur Heart J. 1992;13(Suppl D):56–61.PubMedCrossRefGoogle Scholar
  112. 112.
    Barger PM, Kelly DP. Fatty acid utilization in the hypertrophied and failing heart: molecular regulatory mechanisms. Am J Med Sci. 1999;318(1):36–42.PubMedCrossRefGoogle Scholar
  113. 113.
    Tuder RM, Davis LA, Graham BB. Targeting energetic metabolism: a new frontier in the pathogenesis and treatment of pulmonary hypertension. Am J Respir Crit Care Med. 2012;185(3):260–6.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Kolwicz SC Jr. And R. Tian, glucose metabolism and cardiac hypertrophy. Cardiovasc Res. 2011;90(2):194–201.PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Taegtmeyer H, et al. Linking gene expression to function: metabolic flexibility in the normal and diseased heart. Ann N Y Acad Sci. 2004;1015:202–13.PubMedCrossRefGoogle Scholar
  116. 116.
    Jamshidi Y, et al. Peroxisome proliferator-activated receptor alpha gene regulates left ventricular growth in response to exercise and hypertension. Circulation. 2002;105(8):950–5.PubMedCrossRefGoogle Scholar
  117. 117.
    Blair E, et al. Mutations in the gamma(2) subunit of AMP-activated protein kinase cause familial hypertrophic cardiomyopathy: evidence for the central role of energy compromise in disease pathogenesis. Hum Mol Genet. 2001;10(11):1215–20.PubMedCrossRefGoogle Scholar
  118. 118.
    Razeghi P, et al. Downregulation of myocardial myocyte enhancer factor 2C and myocyte enhancer factor 2C-regulated gene expression in diabetic patients with nonischemic heart failure. Circulation. 2002;106(4):407–11.PubMedCrossRefGoogle Scholar
  119. 119.
    Buttrick PM, et al. Alterations in gene expression in the rat heart after chronic pathological and physiological loads. J Mol Cell Cardiol. 1994;26(1):61–7.PubMedCrossRefGoogle Scholar
  120. 120.
    Ouwens DM, et al. Cardiac contractile dysfunction in insulin-resistant rats fed a high-fat diet is associated with elevated CD36-mediated fatty acid uptake and esterification. Diabetologia. 2007;50(9):1938–48.PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Handa N, et al. Quantitative FDG-uptake by positron emission tomography in progressive hypertrophy of rat hearts in vivo. Ann Nucl Med. 2007;21(10):569–76.PubMedCrossRefGoogle Scholar
  122. 122.
    Banke NH, et al. Sexual dimorphism in cardiac triacylglyceride dynamics in mice on long term caloric restriction. J Mol Cell Cardiol. 2012;52(3):733–40.PubMedCrossRefGoogle Scholar
  123. 123.
    Hollingsworth KG, et al. Left ventricular torsion, energetics, and diastolic function in normal human aging. Am J Physiol Heart Circ Physiol. 2012;302(4):H885–92.PubMedCrossRefGoogle Scholar
  124. 124.
    van der Meer RW, et al. The ageing male heart: myocardial triglyceride content as independent predictor of diastolic function. Eur Heart J. 2008;29(12):1516–22.PubMedCrossRefGoogle Scholar
  125. 125.
    Zhong M, et al. Quantitative PET imaging detects early metabolic remodeling in a mouse model of pressure-overload left ventricular hypertrophy in vivo. J Nucl Med. 2013;54(4):609–15.PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    de las Fuentes L, et al. Myocardial fatty acid metabolism: independent predictor of left ventricular mass in hypertensive heart disease. Hypertension. 2003; 41(1): 83–7.Google Scholar
  127. 127.
    Hamirani YS, et al. Noninvasive detection of early metabolic left ventricular remodeling in systemic hypertension. Cardiology. 2016;133(3):157–62.PubMedCrossRefGoogle Scholar
  128. 128.
    Lundgrin EL, et al. Fasting 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography to detect metabolic changes in pulmonary arterial hypertension hearts over 1 year. Ann Am Thorac Soc. 2013;10(1):1–9.PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Bokhari S, et al. PET imaging may provide a novel biomarker and understanding of right ventricular dysfunction in patients with idiopathic pulmonary arterial hypertension. Circ Cardiovasc Imaging. 2011;4(6):641–7.PubMedCrossRefGoogle Scholar
  130. 130.
    Fang W, et al. Comparison of 18F-FDG uptake by right ventricular myocardium in idiopathic pulmonary arterial hypertension and pulmonary arterial hypertension associated with congenital heart disease. Pulm Circ. 2012;2(3):365–72.PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Tatebe S, et al. Enhanced [18F]fluorodeoxyglucose accumulation in the right ventricular free wall predicts long-term prognosis of patients with pulmonary hypertension: a preliminary observational study. Eur Heart J Cardiovasc Imaging. 2014;15(6):666–72.PubMedCrossRefGoogle Scholar
  132. 132.
    Oikawa M, et al. Increased [18F]fluorodeoxyglucose accumulation in right ventricular free wall in patients with pulmonary hypertension and the effect of epoprostenol. J Am Coll Cardiol. 2005;45(11):1849–55.PubMedCrossRefGoogle Scholar
  133. 133.
    Mielniczuk LM, et al. Relation between right ventricular function and increased right ventricular [18F]fluorodeoxyglucose accumulation in patients with heart failure. Circ Cardiovasc Imaging. 2011;4(1):59–66.PubMedCrossRefGoogle Scholar
  134. 134.
    Nakae I, et al. Iodine-123 BMIPP scintigraphy in the evaluation of patients with heart failure. Acta Radiol. 2006;47(8):810–6.PubMedCrossRefGoogle Scholar
  135. 135.
    Davila-Roman VG, et al. Altered myocardial fatty acid and glucose metabolism in idiopathic dilated cardiomyopathy. J Am Coll Cardiol. 2002;40(2):271–7.PubMedCrossRefGoogle Scholar
  136. 136.
    Kadkhodayan, A., et al., Sex affects myocardial blood flow and fatty acid substrate metabolism in humans with nonischemic heart failure. J Nucl Cardiol, 2016.Google Scholar
  137. 137.
    Tuunanen H, et al. Decreased myocardial free fatty acid uptake in patients with idiopathic dilated cardiomyopathy: evidence of relationship with insulin resistance and left ventricular dysfunction. J Card Fail. 2006;12(8):644–52.PubMedCrossRefGoogle Scholar
  138. 138.
    Sharma S, et al. Intramyocardial lipid accumulation in the failing human heart resembles the lipotoxic rat heart. FASEB J. 2004;18(14):1692–700.PubMedCrossRefGoogle Scholar
  139. 139.
    Thackery J, dR, Beanlands R, DaSilva J. Early diabetes therapy does not prevent sympathetic dysinnervation in the streptozocin diabetic rat. J Nucl Cardiol. 2014.Google Scholar
  140. 140.
    Vinik AI, Maser RE, Ziegler D. Neuropathy: the crystal ball for cardiovascular disease? Diabetes Care. 2010;33(7):1688–90.PubMedPubMedCentralCrossRefGoogle Scholar
  141. 141.
    Boulton AJ, et al. Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care. 2005;28(4):956–62.PubMedCrossRefGoogle Scholar
  142. 142.
    Tuunanen H, et al. Trimetazidine, a metabolic modulator, has cardiac and extracardiac benefits in idiopathic dilated cardiomyopathy. Circulation. 2008;118(12):1250–8.PubMedCrossRefGoogle Scholar
  143. 143.
    Lepore, J.J., et al., Effects of the novel long-acting GLP-1 agonist, Albiglutide, on cardiac function, cardiac metabolism, and exercise capacity in patients with chronic heart failure and reduced ejection fraction. JACC Heart Fail, 2016.Google Scholar
  144. 144.
    Atherton HJ, et al. Role of pyruvate dehydrogenase inhibition in the development of hypertrophy in the hyperthyroid rat heart: a combined magnetic resonance imaging and hyperpolarized magnetic resonance spectroscopy study. Circulation. 2011;123(22):2552–61.PubMedPubMedCentralCrossRefGoogle Scholar
  145. 145.
    Brown MA, Myears DW, Bergmann SR. Validity of estimates of myocardial oxidative metabolism with carbon-11 acetate and positron emission tomography despite altered patterns of substrate utilization. J Nucl Med. 1989;30(2):187–93.PubMedGoogle Scholar
  146. 146.
    Walsh MN, et al. Noninvasive estimation of regional myocardial oxygen consumption by positron emission tomography with carbon-11 acetate in patients with myocardial infarction. J Nucl Med. 1989;30(11):1798–808.PubMedGoogle Scholar
  147. 147.
    Buxton DB, et al. Radiolabeled acetate as a tracer of myocardial tricarboxylic acid cycle flux. Circ Res. 1988;63(3):628–34.PubMedCrossRefGoogle Scholar
  148. 148.
    Koellisch U, et al. Metabolic imaging of hyperpolarized [1-(13) C]acetate and [1-(13) C]acetylcarnitine - investigation of the influence of dobutamine induced stress. Magn Reson Med. 2015;74(4):1011–8.PubMedCrossRefGoogle Scholar
  149. 149.
    Bastiaansen JA, Merritt ME, Comment A. Measuring changes in substrate utilization in the myocardium in response to fasting using hyperpolarized [1-(13)C]butyrate and [1-(13)C]pyruvate. Sci Rep. 2016;6:25573.PubMedPubMedCentralCrossRefGoogle Scholar
  150. 150.
    Erguven M, et al. A case of early diagnosed carnitine deficiency presenting with respiratory symptoms. Ann Nutr Metab. 2007;51(4):331–4.PubMedCrossRefGoogle Scholar
  151. 151.
    Rinaldo P, Matern D, Bennett MJ. Fatty acid oxidation disorders. Annu Rev Physiol. 2002;64:477–502.PubMedCrossRefGoogle Scholar
  152. 152.
    Palmieri F. Diseases caused by defects of mitochondrial carriers: a review. Biochim Biophys Acta. 2008;1777(7-8):564–78.PubMedCrossRefGoogle Scholar
  153. 153.
    Cave MC, et al. Obesity, inflammation, and the potential application of pharmaconutrition. Nutr Clin Pract. 2008;23(1):16–34.PubMedCrossRefGoogle Scholar
  154. 154.
    Kenchaiah S, et al. Obesity and the risk of heart failure. N Engl J Med. 2002;347(5):305–13.PubMedCrossRefGoogle Scholar
  155. 155.
    Wong CY, et al. Alterations of left ventricular myocardial characteristics associated with obesity. Circulation. 2004;110(19):3081–7.PubMedCrossRefGoogle Scholar
  156. 156.
    Zhou YT, et al. Lipotoxic heart disease in obese rats: implications for human obesity. Proc Natl Acad Sci U S A. 2000;97(4):1784–9.PubMedPubMedCentralCrossRefGoogle Scholar
  157. 157.
    Commerford SR, et al. Fat oxidation, lipolysis, and free fatty acid cycling in obesity-prone and obesity-resistant rats. Am J Physiol Endocrinol Metab. 2000;279(4):E875–85.PubMedGoogle Scholar
  158. 158.
    Boudina S, Abel ED. Diabetic cardiomyopathy revisited. Circulation. 2007;115(25): 3213–23.Google Scholar
  159. 159.
    Severson DL. Diabetic cardiomyopathy: recent evidence from mouse models of type 1 and type 2 diabetes. Can J Physiol Pharmacol. 2004;82(10):813–23.PubMedCrossRefGoogle Scholar
  160. 160.
    Stanley WC, Lopaschuk GD, McCormack JG. Regulation of energy substrate metabolism in the diabetic heart. Cardiovasc Res. 1997;34(1):25–33.PubMedCrossRefGoogle Scholar
  161. 161.
    Taegtmeyer H, McNulty P, Young ME. Adaptation and maladaptation of the heart in diabetes: part I: general concepts. Circulation. 2002;105(14):1727–33.PubMedCrossRefGoogle Scholar
  162. 162.
    Young ME, McNulty P, Taegtmeyer H. Adaptation and maladaptation of the heart in diabetes: part II: potential mechanisms. Circulation. 2002;105(15):1861–70.PubMedCrossRefGoogle Scholar
  163. 163.
    Itani SI, et al. Involvement of protein kinase C in human skeletal muscle insulin resistance and obesity. Diabetes. 2000;49(8):1353–8.PubMedCrossRefGoogle Scholar
  164. 164.
    Ruderman NB, et al. Malonyl-CoA, fuel sensing, and insulin resistance. Am J Phys. 1999;276(1 Pt 1):E1–E18.Google Scholar
  165. 165.
    Schmitz-Peiffer C, Craig DL, Biden TJ. Ceramide generation is sufficient to account for the inhibition of the insulin-stimulated PKB pathway in C2C12 skeletal muscle cells pretreated with palmitate. J Biol Chem. 1999;274(34):24202–10.PubMedCrossRefGoogle Scholar
  166. 166.
    Oakes ND, et al. Cardiac metabolism in mice: tracer method developments and in vivo application revealing profound metabolic inflexibility in diabetes. Am J Physiol Endocrinol Metab. 2006;290(5):E870–81.PubMedCrossRefGoogle Scholar
  167. 167.
    Young ME, et al. Impaired long-chain fatty acid oxidation and contractile dysfunction in the obese Zucker rat heart. Diabetes. 2002;51(8):2587–95.PubMedCrossRefGoogle Scholar
  168. 168.
    Peterson LR, et al. Effect of obesity and insulin resistance on myocardial substrate metabolism and efficiency in young women. Circulation. 2004;109(18):2191–6.PubMedCrossRefGoogle Scholar
  169. 169.
    Buchanan J, et al. Reduced cardiac efficiency and altered substrate metabolism precedes the onset of hyperglycemia and contractile dysfunction in two mouse models of insulin resistance and obesity. Endocrinology. 2005;146(12):5341–9.PubMedCrossRefGoogle Scholar
  170. 170.
    Mazumder PK, et al. Impaired cardiac efficiency and increased fatty acid oxidation in insulin-resistant ob/ob mouse hearts. Diabetes. 2004;53(9):2366–74.PubMedCrossRefGoogle Scholar
  171. 171.
    Boudina S, Abel ED. Mitochondrial uncoupling: a key contributor to reduced cardiac efficiency in diabetes. Physiology (Bethesda). 2006;21:250–8.CrossRefGoogle Scholar
  172. 172.
    Boudina S, et al. Reduced mitochondrial oxidative capacity and increased mitochondrial uncoupling impair myocardial energetics in obesity. Circulation. 2005;112(17):2686–95.PubMedCrossRefGoogle Scholar
  173. 173.
    How OJ, et al. Increased myocardial oxygen consumption reduces cardiac efficiency in diabetic mice. Diabetes. 2006;55(2):466–73.PubMedCrossRefGoogle Scholar
  174. 174.
    Peterson LR, et al. Impact of gender on the myocardial metabolic response to obesity. J Am Coll Cardiol Imaging. 2008;1:424–33.CrossRefGoogle Scholar
  175. 175.
    Peterson LR, et al. Type 2 diabetes, obesity, and sex difference affect the fate of glucose in the human heart. Am J Physiol Heart Circ Physiol. 2015;308(12):H1510–6.PubMedPubMedCentralCrossRefGoogle Scholar
  176. 176.
    Viljanen AP, et al. Effect of caloric restriction on myocardial fatty acid uptake, left ventricular mass, and cardiac work in obese adults. Am J Cardiol. 2009;103(12):1721–6.PubMedCrossRefGoogle Scholar
  177. 177.
    Lin CH, et al. Myocardial oxygen consumption change predicts left ventricular relaxation improvement in obese humans after weight loss. Obesity (Silver Spring). 2011;19(9):1804–12.CrossRefGoogle Scholar
  178. 178.
    Finck BN, et al. The cardiac phenotype induced by PPARalpha overexpression mimics that caused by diabetes mellitus. J Clin Invest. 2002;109(1):121–30.PubMedPubMedCentralCrossRefGoogle Scholar
  179. 179.
    Burkart EM, et al. Nuclear receptors PPARbeta/delta and PPARalpha direct distinct metabolic regulatory programs in the mouse heart. J Clin Invest. 2007;117(12):3930–9.PubMedPubMedCentralGoogle Scholar
  180. 180.
    Shoghi KI, et al. Time course of alterations in myocardial glucose utilization in the Zucker diabetic fatty rat with correlation to gene expression of glucose transporters: a small-animal PET investigation. J Nucl Med. 2008;49(8):1320–7.PubMedPubMedCentralCrossRefGoogle Scholar
  181. 181.
    van den Brom CE, et al. Altered myocardial substrate metabolism is associated with myocardial dysfunction in early diabetic cardiomyopathy in rats: studies using positron emission tomography. Cardiovasc Diabetol. 2009;8:39.PubMedPubMedCentralCrossRefGoogle Scholar
  182. 182.
    Thorn SL, et al. Repeatable noninvasive measurement of mouse myocardial glucose uptake with 18F-FDG: evaluation of tracer kinetics in a type 1 diabetes model. J Nucl Med. 2013;54(9):1637–44.PubMedCrossRefGoogle Scholar
  183. 183.
    Herrero P, et al. PET detection of the impact of dobutamine on myocardial glucose metabolism in women with type 1 diabetes mellitus. J Nucl Cardiol. 2008;15(6):791–9.PubMedPubMedCentralCrossRefGoogle Scholar
  184. 184.
    Peterson LR, et al. Fatty acids and insulin modulate myocardial substrate metabolism in humans with type 1 diabetes. Diabetes. 2008;57(1):32–40.PubMedCrossRefGoogle Scholar
  185. 185.
    Rijzewijk LJ, et al. Altered myocardial substrate metabolism and decreased diastolic function in nonischemic human diabetic cardiomyopathy: studies with cardiac positron emission tomography and magnetic resonance imaging. J Am Coll Cardiol. 2009;54(16):1524–32.PubMedCrossRefGoogle Scholar
  186. 186.
    Peterson LR, et al. Sex and type 2 diabetes: obesity-independent effects on left ventricular substrate metabolism and relaxation in humans. Obesity (Silver Spring). 2012;20(4):802–10.CrossRefGoogle Scholar
  187. 187.
    Monti LD, et al. Myocardial insulin resistance associated with chronic hypertriglyceridemia and increased FFA levels in type 2 diabetic patients. Am J Physiol Heart Circ Physiol. 2004;287(3):H1225–31.PubMedCrossRefGoogle Scholar
  188. 188.
    McGill JB, et al. Potentiation of abnormalities in myocardial metabolism with the development of diabetes in women with obesity and insulin resistance. J Nucl Cardiol. 2011;18(3):421–9. quiz 432-3PubMedCrossRefGoogle Scholar
  189. 189.
    Rijzewijk LJ, et al. Myocardial steatosis is an independent predictor of diastolic dysfunction in type 2 diabetes mellitus. J Am Coll Cardiol. 2008;52(22):1793–9.PubMedCrossRefGoogle Scholar
  190. 190.
    Rijzewijk LJ, et al. Effects of hepatic triglyceride content on myocardial metabolism in type 2 diabetes. J Am Coll Cardiol. 2010;56(3):225–33.PubMedCrossRefGoogle Scholar
  191. 191.
    Ng AC, et al. Myocardial steatosis and biventricular strain and strain rate imaging in patients with type 2 diabetes mellitus. Circulation. 2010;122(24):2538–44.PubMedCrossRefGoogle Scholar
  192. 192.
    MacDonald MR, et al. Discordant short- and long-term outcomes associated with diabetes in patients with heart failure: importance of age and sex: a population study of 5.1 million people in Scotland. Circ Heart Fail. 2008;1(4):234–41.PubMedCrossRefGoogle Scholar
  193. 193.
    Ho KK, et al. The epidemiology of heart failure: the Framingham study. J Am Coll Cardiol. 1993;22(4 Suppl A):6A–13A.PubMedCrossRefGoogle Scholar
  194. 194.
    Gu K, Cowie CC, Harris MI. Diabetes and decline in heart disease mortality in US adults. JAMA. 1999;281(14):1291–7.PubMedCrossRefGoogle Scholar
  195. 195.
    van der Meer RW, et al. Pioglitazone improves cardiac function and alters myocardial substrate metabolism without affecting cardiac triglyceride accumulation and high-energy phosphate metabolism in patients with well-controlled type 2 diabetes mellitus. Circulation. 2009;119(15):2069–77.PubMedCrossRefGoogle Scholar
  196. 196.
    Hallsten K, et al. Enhancement of insulin-stimulated myocardial glucose uptake in patients with type 2 diabetes treated with rosiglitazone. Diabet Med. 2004;21(12):1280–7.PubMedCrossRefGoogle Scholar
  197. 197.
    Koellisch U, et al. Investigation of metabolic changes in STZ-induced diabetic rats with hyperpolarized [1-13C]acetate. Physiol Rep. 2015;3(8):e12474.PubMedPubMedCentralCrossRefGoogle Scholar
  198. 198.
    Wilson CR, et al. Western diet, but not high fat diet, causes derangements of fatty acid metabolism and contractile dysfunction in the heart of Wistar rats. Biochem J. 2007;406(3):457–67.PubMedPubMedCentralCrossRefGoogle Scholar
  199. 199.
    Qin F, et al. The polyphenols resveratrol and S17834 prevent the structural and functional sequelae of diet-induced metabolic heart disease in mice. Circulation. 2012;125(14):1757–64. S1-6PubMedPubMedCentralCrossRefGoogle Scholar
  200. 200.
    Vasanji Z, et al. Alterations in cardiac contractile performance and sarcoplasmic reticulum function in sucrose-fed rats is associated with insulin resistance. Am J Physiol Cell Physiol. 2006;291(4):C772–80.PubMedCrossRefGoogle Scholar
  201. 201.
    Crewe C, Kinter M, Szweda LI. Rapid inhibition of pyruvate dehydrogenase: an initiating event in high dietary fat-induced loss of metabolic flexibility in the heart. PLoS One. 2013;8(10):e77280.PubMedPubMedCentralCrossRefGoogle Scholar
  202. 202.
    Seymour AM, et al. In vivo assessment of cardiac metabolism and function in the abdominal aortic banding model of compensated cardiac hypertrophy. Cardiovasc Res. 2015;106(2):249–60.PubMedPubMedCentralCrossRefGoogle Scholar
  203. 203.
    Mankoff DA, et al. Molecular imaging research in the outcomes era: measuring outcomes for individualized cancer therapy. Acad Radiol. 2007;14(4):398–405.PubMedPubMedCentralCrossRefGoogle Scholar
  204. 204.
    McShane LM, Hayes DF. Publication of tumor marker research results: the necessity for complete and transparent reporting. J Clin Oncol. 2012;30(34):4223–32.PubMedPubMedCentralCrossRefGoogle Scholar
  205. 205.
    Henry NL, Hayes DF. Cancer biomarkers. Mol Oncol. 2012;6(2):140–6.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Division of Radiological SciencesMallinckrodt Institute of Radiology, Washington University School of MedicineSt. LouisUSA
  2. 2.Departments of Radiology and Internal MedicineAdvanced Imaging Research Center, University of Texas Southwestern Medical CenterDallasUSA
  3. 3.VA North Texas Health Care SystemDallasUSA

Personalised recommendations