Assessment of Human-Liver Metabolism by P-31 Magnetic-Resonance Spectroscopy

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 (P(i)) 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 μM, respectively. During intravenous fructose tolerance tests the hepatic concentrations of sugar phosphates, ATP and P(i) 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 P(i) and ATP decreased by three- to fourfold. Metabolism of sugar phosphates was complete within 20 min and could be followed by P MR with a time resolution of 5 min. Thus, P 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, P MR spectroscopy may provide a means for the functional assessment of the liver

Biochemical investigation of human tumours in vivo with phosphorus-31 magnetic resonance spectroscopy.

The bioenergetic state of 15 human tumours was examined with phosphorus-31 magnetic resonance spectroscopy. A striking diversity in metabolic patterns was observed, and significant differences from normal tissue were seen in all cases. A common feature was an elevation of intracellular pH, which may be related to an increase in Na+/H+ exchange during cell activation. It is unlikely that the patterns observed directly correlate with malignancy, but characterisation of the energetic state of a given tumour in a given physiological environment may help in the design and evaluation of interventions for that specific case

The Study of Human Organs by P-31 Topical Magnetic-Resonance Spectroscopy

The potential clinical use of topical magnetic resonance spectroscopy (volume selection by static magnetic field gradients) was tested in 50 studies in volunteers. Topical magnetic resonance spectroscopy (MRS) was shown to be a straightforward method for localising 31P spectra of brain and liver. However, the spherical shape and fixed position of the selected volume posed serious limitations to the study of heart and transplanted kidney by topical MRS. Phosphorus-31 spectra of approximately 30 cm-3 of brain or liver could be obtained in 8 min. Ratios of metabolite concentrations could be determined with a coefficient of variation ranging from 10% to 30%. The ratios of phosphocreatine/ATP and inorganic phosphate/ATP in brain were 1.8 and 0.3, respectively. The ratio of inorganic phosphate/ATP in liver was 0.9. Intracellular pH was 7.03 in brain and 7.24 in liver. The T1 relaxation times of phosphocreatine, inorganic phosphate and gamma-ATP in brain were 4.8 s, 2.5 s and 1.0 s, respectively

An unusual metabolic myopathy: a malate-aspartate shuttle defect.

Studies on a 27-year-old man with a 3-year history of exercise-induced muscle pain, passage of red urine and elevated serum creatine kinase are described. Histological examination of a biopsy from quadriceps revealed non-specific myopathic changes with occasional clusters of subsarcolemmal mitochondria. The phosphorylase stain was normal. Phosphorous nuclear magnetic resonance (NMR) spectroscopy studies of gastrocnemius and flexor digitorum superficialis muscles showed no abnormalities at rest. During aerobic exercise there was an abnormally rapid decrease in phosphocreatine concentration but the pH remained within the normal range. There was a build-up of phosphomonoester (probably glucose 6-phosphate), usually indicative of a block in glycolysis. However, a primary defect in the glycolytic pathway seemed unlikely because muscle acidified normally during ischaemic exercise. Recovery from exercise was unusual in that phosphocreatine resynthesis and inorganic phosphate disappearance followed similar prolonged time courses (in control subjects the rate of inorganic phosphate disappearance was about twice as fast as the rate of phosphocreatine resynthesis). The transport of inorganic phosphate into the mitochondria appeared to be delayed. These slow recovery data suggested that oxidative metabolism was impaired. However, with all substrates tested, isolated muscle mitochondria had rates of oxygen uptake that were similar to control values, thereby ruling out a primary defect in mitochondrial respiration. A system involving several mitochondrial transport systems, the malate-aspartate shuttle, was measured. The activity in the patient's isolated mitochondria was less than 20% of the activity present in samples from control subjects. This patient is the only one so far reported with a defect involving the malate-aspartate shuttle system

Invivo High-Resolution Volume-Selected Proton Spectroscopy and T1 Measurements in the Dog Brain

Successful in vivo NMR spectroscopy requires a combination of techniques to address the problems of volume selection, water suppression, and resolution. All this needs to be done in the very heterogeneous environment found in living organisms. Previously published techniques are used to obtain H spectra from a dog brain, observing metabolites with concentrations below 1 mM. Measurements of spin‐lattice relaxation times (T) are also presented. The H relaxation times are long (T > 1.0 s) yielding information about the fluidity of the molecular environment. Comments are made concerning the achievable linewidth in vivo and the deficiencies that phase‐encoding spectroscopic methods may have in obtaining high‐resolution H spectra. © 1989 Academic Press, Inc