Quantitative studies of human cardiac metabolism by 31P rotating-frame NMR.

Abstract

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...

Human primary brain tumour metabolism in vivo: a phosphorus magnetic resonance spectroscopy study

“…The two coils were isolated from each other using a circuit described previously (Styles, 1988). In all studies the magnetic field homogeneity was first optimised using the proton signal from the region of brain to be studied.The PMRFI technique has been described in detail elsewhere (Blackledge et al, 1987). The pulse sequence consisted of 0+x±, Ay, acquire, relaxation delay.…”

“…The phase modulated rotating frame imaging (PMRFI) technique was used (Blackledge et al, 1987) in which a double surface coil, placed over the region of interest, receives signal from a defined cylinder of tissue 6 cm in diameter to a depth of 6cm. The cylinder is resolved into small biconvex discs, approximately 6cm wide and 0.5cm deep.…”

Mitral Regurgitation

“…Metabolite ratios were cross-checked blindly by two independent investigators. All PCr/ATP calculations were based on the gamma ATP resonance 4,8 because of off-resonance effects on the ␤ATP peak in some patients.…”

“…The latter plot (Figure 3) reveals the prominent PCr and higher PCr/ATP in the chest wall and demonstrates the transition to the lower ratios characteristic of the myocardium. 3,4,7,26 Spectral analysis: PMRFI and 1D CSI spectra were quantified by measuring peak areas by triangulation and by automated curve fitting in the frequency domain with standard Bruker Instrument integration software. Metabolite ratios were cross-checked blindly by two independent investigators.…”

“…Abnormal high-energy phosphorus and other metabolism appears to play a role, 1,2 and several recent reports using 31 P MRS [3][4][5][6] describe altered PCr/ATP among patients with aortic valve disease, 7,8 cardiomyopathy, 9,10 ischemia, [11][12][13] and other disorders affecting the LV (for reviews, see References 14 through 16).…”