Biochemical Specificity in Human Cardiac Imaging by 13C Magnetic Resonance Imaging
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Energy contained in lactate, glucose, ketones, and fatty acids is captured by metabolic processes in the heart to produce mechanical and electric work.1 The actual contribution of each substrate to energy production and the specific metabolic pathways involved is sensitive to both physiological conditions and disease. This knowledge of cardiac biochemistry is derived primarily from studies in isolated hearts and from invasive in vivo studies in experimental animals. Animal models of some diseases, notably acute ischemia and reperfusion, provided valuable insights, but in general, the relevance of animal studies to human disease is uncertain because it is difficult to meaningfully model heart failure, hypertrophy, cardiomyopathies, hibernating myocardium, and other complex conditions. Methods to quantify biochemical events in the heart are important because it is becoming increasingly apparent that chronic adaptations in metabolism may drive processes with adverse consequences, such as impaired energy capture and oxidative stress. Positron tomography provides some metabolic information in patients. However, in spite of the popularity and the high sensitivity for detecting a radionuclide, the fit between metabolic complexity and the information accessible by positron tomography is actually poor. For example, uptake, phosphorylation, and trapping of 18FDG is widely accepted as a biomarker of glucose metabolism. Yet, the positron tomography signal does not inherently make the simple distinction between metabolism of glucose to acetyl-CoA and subsequent oxidation in the Krebs cycle versus anaerobic glycolysis to pyruvate and lactate. For basic science studies, an alternative to radiotracers is the use of 13C-enriched substrates with detection by nuclear magnetic resonance (NMR) spectroscopy. 13C is a stable isotope of carbon that is normally present at ≈1% of carbon nuclei. After enriching a compound with 13C to ≈99%, intermediary metabolism has been studied for decades using 13C NMR spectroscopy.2 Aside from the convenience …