We have developed 31P NMR spectroscopic methods to determine quantitatively relative levels of phosphorous-containing metabolites in the human myocardium. We have used localization techniques based on the rotating-frame imaging experiment and carried out with a double-surface coil probe. Information is obtained from selected slices by rotatingframe depth selection and from a complete one-dimensional spectroscopic image using phase-modulated rotating-frame imaging. The methods collect biochemical information from metabolites in human heart, and we use the fact that the phosphocreatine/ATP molar ratio in skeletal muscle at rest is higher than that in working heart to demonstrate that localization has been achieved for each investigation. The phosphocreatine/ATP molar ratio in normal human heart has been measured as 1.55 ± 0.20 (mean + SD) (3.5-sec interpulse delay) in six subjects using depth selection and as 1.53 ± 0.25 (mean + SD) in four subjects using spectroscopic imaging. Measurement of this ratio is expected to give a useful and reproducible index of myocardial energetics in normal and pathological states.It has been shown that 31P NMR spectroscopy provides a useful insight into myocardial energetics using isolated and perfused rat hearts (1-3). In particular, the relative concentrations of phosphocreatine (PCr), ATP, and Pi, as well as intracellular pH, can yield information about the relationship between ATP supply and demand and give insight into metabolic control. It has also been shown that 31P NMR spectra from the hearts of live rats were qualitatively similar to those of the isolated perfused organ, but differed quantitatively in that the PCr/ATP molar ratio was 30% higher in vivo than for the isolated heart (4). A similarly high PCr/ATP molar ratio of 1.7 was observed in the canine heart, by using a catheter coil, which removed the necessity for surgery (5).The first spectroscopic investigation of human heart was performed on infants, where localization was achieved by simply using a surface coil probe. A PCr/ATP molar ratio of 2.0 ± 0.1 was reported in a healthy 18-month-old child compared to a lower value of 1.3 in an 8-month-old child with cardiomegaly (6). In contrast, using depth-resolved spectroscopy, the PCr/ATP molar ratio was found to be 1.3 ± 0.4 in a single adult (7). Accurate, rapid, and reproducible measurements of PCr/ATP ratio will be essential in the investigation of human heart disease by 31P NMR. The development of differential localization techniques have made such measurements theoretically possible in human subjects (8)(9)(10)(11)(12).The specific problems associated with investigating the human heart using 31P NMR include the achievement of adequate spatial localization and establishment of objective criteria to ensure that the data obtained are representative of cardiac muscle. Any contamination by a signal from overlying skeletal muscle will distort the measured PCr/ATP ratio, as studies show that this ratio in skeletal muscle is very different from that in cardiac mu...
Phosphorus 31 magnetic resonance (MR) spectroscopy was used for the study of liver metabolism in vivo in seven healthy subjects. Subjects were examined in a 1.6 T whole-body magnet using surface coils for data acquisition. The region of the liver from which MR signals were collected was selected by magnetic-field profiling. The concentration ratios of adenosine triphosphate (ATP), inorganic phosphate (Pi) and sugar phosphates contained in liver cells could be reproducibly assessed. Cytosolic pH and the free magnesium concentration were determined to be 7.18 and 300 microM, respectively. During intravenous fructose tolerance tests the hepatic concentrations of sugar phosphates, ATP and Pi altered markedly. During the first 5 min following bolus injection of 250 mg fructose/kg body weight the concentration of sugar phosphates increased sevenfold whereas Pi and ATP decreased by three- to fourfold. Metabolism of sugar phosphates was complete within 20 min and could be followed by 31P MR with a time resolution of 5 min. Thus, 31P MR spectroscopy yields insight into liver metabolism which has not been accessible so far using conventional non-invasive methods. In conjunction with intravenous fructose loading, 31P MR spectroscopy may provide a means for the functional assessment of the liver.
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