Electrocardiogram monitoring at rest and during exercise in 31P magnetic resonance spectroscopy studies of the human heart at 1.9 tesla.

An electrocardiogram (ECG) monitoring system has been developed and evaluated in normal volunteers (n = 7) and patients with various cardiac diseases (n = 24) in a 1.9 tesla magnet during magnetic resonance spectroscopy studies. To minimize an ECG signal path, and thus to reduce motion-related artifacts on the ECG during a dynamic exercise test, one coaxial cable was used to obtain the ECG signal from two electrodes placed parallel to the longitudinal body axis on the left side of the chest. A fiber optic link and an inductor-capacitor low-pass filter were used to remove extraneous radiofrequency (RF) noise and RF pulse artifacts respectively, and the examination bed was solidly supported on the base of the magnet. The ECG monitoring system provided a useful means for continuous recording of the ECG independently of the R-R interval in the high magnetic field, and permitted reliable monitoring of the QRS complex of the subject at rest and during exercise.

Global and depth resolved phosphorus magnetic resonance spectroscopy to predict outcome after birth asphyxia.

Twelve normal and 32 asphyxiated neonates were studied using global and depth resolved phosphorus magnetic resonance spectroscopy (31PMRS). Eight of the asphyxiated group died or survived with major neurodevelopmental abnormalities. A global phosphocreatinine/inorganic phosphate (PCr/Pi) ratio below the range of values from normal infants predicted adverse outcome after asphyxia with a positive predictive value of 64%, sensitivity 88%, and specificity 83%. Corresponding values for global inorganic orthophosphate/adenosine triphosphate (Pi/ATP) ratios were positive predictive value 88%, sensitivity 96%, and specificity 88%. Spatially localised MRS data, obtained using phase modulated rotating frame imaging, showed cerebral energy metabolism to be more abnormal in deep than superficial regions after birth asphyxia. However, in this population of full term infants none of the regional metabolite concentrations were superior to global data for prediction of outcome.

31P-NMR study of brain phospholipid structures in vivo.

31P-NMR has been used extensively for the study of cytosolic small molecule phosphates in vivo and phospholipid structures in vitro. We present in this paper a series of studies of the brain by 31P-NMR, both in vivo and in extracts, showing the information that can be derived about phospholipids. 31P-NMR spectra of mouse brain at 73 mHz are characterised by almost a complete absence of the large phosphodiester peak in comparison to equivalent spectra at 32 mHz. Proton decoupled spectra in vivo, and spectra of extracts, show that the phosphodiester peak observed in 32 mHz spectra in vivo is mainly due to phospholipid bilayers. Homogenates of quaking and control mouse brains, and of bovine grey matter, show another narrower phosphodiester peak possibly from small phospholipid vesicles. This peak is increased in intensity in the affected mice. These experiments demonstrate the presence of three major components contributing to the phosphodiester resonance: bilayer phospholipids, more mobile phospholipids, and the freely soluble cytosolic molecules glycerophosphocholine and glycerophosphoethanolamine. These NMR methods for non-invasive investigation of phospholipid structures in the brain might be extended to studies of patients with membrane involved diseases such as multiple sclerosis.

Spatially localized magnetic resonance spectroscopy of the brains of normal and asphyxiated newborns.

Phase-modulated rotating frame imaging is a modification of magnetic resonance spectroscopy, which uses a linear radiofrequency field gradient to obtain spatially localized biochemical information. Phase-modulated rotating frame imaging was used to study regional cerebral energy metabolism in the brains of 9 normal newborns and 25 newborns after birth asphyxia. Relative concentrations of phosphorus-containing metabolites and intracellular pH were determined for brain tissue at three specified depths below the brain surface for all neonates. Wide variations in metabolite ratios were seen among normal neonates, and considerable metabolic heterogeneity was demonstrated in individual neonates by depth-resolved spectroscopy. Asphyxiated neonates with severe hypoxic-ischemic encephalopathy and a poor neurodevelopmental outcome showed the expected rise in inorganic orthophosphate and fall in phosphocreatine concentrations in both global and spatially localized spectra. Phase-modulated rotating frame imaging showed that metabolic derangement was less in superficial than in deeper brain tissue. The inorganic orthophosphate-adenosine triphosphate ratio from 1 to 2 cm below the brain surface was more accurate than any global metabolite ratio for the identification of neonates with a poor short-term outcome. These data are consistent with the known vulnerability of subcortical brain tissue to hypoxic-ischemic injury in the full-term neonate.

The effects of bilirubin on brain energy metabolism during hyperosmolar opening of the blood-brain barrier: an in vivo study using 31P nuclear magnetic resonance spectroscopy.

Despite intensive investigation it remains uncertain how bilirubin enters the brain and how it exerts a toxic effect on neurones. Studies of induced hyperbilirubinemia in animal models in vivo have failed to reproduce bilirubin encephalopathy without additional factors such as hypoxia, asphyxia, hypercapnia, and disruption of the blood-brain barrier. The aim of this study was to investigate, using 31P NMRS, whether hyperbilirubinemia alone or in association with hyperosmolar opening of the blood-brain barrier caused any disturbance of cerebral energy metabolism in vivo. Spectra were acquired using a surface coil positioned over the right cerebral hemisphere of anaesthetized adult rats placed in the bore of a 1.9 Tesla magnet. Hyperbilirubinemia alone at a maximum mean serum concentration of 1063 +/- 175 mumol/L (mean +/- SD, n = 7) caused no apparent disruption in brain energy metabolism. However, in combination with hyperosmolar blood-brain barrier opening a serum bilirubin concentration of 483 +/- 52 mumol/L (mean +/- SD, n = 9) was associated with a reduction in PCr/(PCr + Pi) ratio from 0.68 +/- 0.06 to 0.44 +/- 0.14 (mean +/- SD, p less than 0.001). A significant correlation was demonstrated between cerebral hemisphere bilirubin content and the reduction in PCr/(PCr + Pi) (r = 0.84, n = 9, p less than 0.01). These results demonstrate in vivo a disruptive effect of bilirubin on cerebral energy metabolism in the presence of an open BBB. This mode of entry and mechanism of toxicity may be factors in the pathophysiology of bilirubin encephalopathy in the newborn infant.

Metabolic changes during experimental cerebral ischemia in hyperglycemic rats, observed by 31P and 1H magnetic resonance spectroscopy.

Progressive cerebral ischemia was induced in seven anesthetized hyperglycemic rats by carotid artery ligation and hemorrhagic hypotension. Phosphorus metabolites, intracellular pH, and lactate in the brain were monitored by 31P and 1H magnetic resonance spectroscopy. Under conditions in which blood flow was low, phosphocreatine (PCr) concentration and intracellular pH decreased and the concentration of lactate increased. The decrease in ATP was approximately one-third that of PCr until only 25% PCr remained, after which ATP was lost more rapidly than PCr. These changes were interpreted in terms of three regions observed by the magnetic resonance coil, one of complete ischemia, one of partial ischemia, and one of perfusion sufficient to maintain normal metabolite levels. The extent of the three regions was estimated quantitatively. Broadening and splitting of the inorganic phosphorus (Pi) peak into two components provided further evidence of distinct populations of cells, one very acidic and another less so. Apparent intracellular buffering capacity was calculated as 23.6 +/- 1.3 mumol lactate/g wet wt/pH.

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

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 rotating-frame 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.