Reto Buchli

Diagnostic and prognostic value of cerebral 31P magnetic resonance spectroscopy in neonates with perinatal asphyxia

The impact of depressed neonatal cerebral oxidative phosphorylation for diagnosing the severity of perinatal asphyxia was estimated by correlating the concentrations of phosphocreatine (PCr) and ATP as determined by magnetic resonance spectroscopy with the degree of hypoxic-ischemic encephalopathy(HIE) in 23 asphyxiated term neonates. Ten healthy age-matched neonates served as controls. In patients, the mean concentrations ±SD of PCr and ATP were 0.99 ± 0.46 mmol/L (1.6 ± 0.2 mmol/L) and 0.99 ± 0.35 mmol/L (1.7 ± 0.2 mmol/L), respectively (normal values in parentheses). [PCr] and [ATP] correlated significantly with the severity of HIE (r = 0.85 and 0.9, respectively, p < 0.001), indicating that the neonatal encephalopathy is the clinical manifestation of a marred brain energy metabolism. Neurodevelopmental outcome was evaluated in 21 children at 3, 9, and 18 mo. Seven infants had multiple impairments, five were moderately handicapped, five had only mild symptoms, and four were normal. There was a significant correlation between the cerebral concentrations of PCr or ATP at birth and outcome (r = 0.8, p < 0.001) and between the degree of neonatal neurologic depression and outcome (r= 0.7). More important, the outcome of neonates with moderate HIE could better be predicted with information from quantitative 31P magnetic resonance spectroscopy than from neurologic examinations. In general, the accuracy of outcome predictability could significantly be increased by adding results from31 P magnetic resonance spectroscopy to the neonatal neurologic score, but not vice versa. No correlation with outcome was found for other perinatal risk factors, including Apgar score.

Developmental changes of phosphorus metabolite concentrations in the human brain : a 31P magnetic resonance spectroscopy study in vivo

ABSTRACT: Phosphorus magnetic resonance spectroscopy is a noninvasive method to investigate brain metabolism in vivo. ATP generally serves as an internal concentration standard for the quantification of the various phosphorus metabolites, because the ATP concentration in mammalian brains is assumed to be age independent. This presumption is based on observations made in the biochemical analysis of the developing rat brain. In the present study, metabolite concentrations were assessed with an external concentration standard. Each brain spectrum was quantified using a calibration spectrum that was acquired from a phantom after the in vivo brain measurement. Fully relaxed localized brain spectra were obtained from 16 neonates (2–28 d), 17 infants (6–20 mo), and 28 adults (22–58 y). The metabolite concentrations (in mmol/L) changed from neonates to adults: phosphomonoester from 4.5 to 3.5, inorganic phosphate from 0.6 to 1.0, phosphodiester from 3.2 to 11.7, phosphocreatine from 1.4 to 3.4, and ATP from 1.6 to 2.9. We conclude that 1) the ATP concentration in the human brain almost doubles between neonates and adults, and 2) ATP may not be used as an age-independent internal concentration standard.

Magnetic resonance imaging of brain edema in the neonatal rat : a comparison of short and long term hypoxia-ischemia

ABSTRACT: Diffusion-weighted and transversal relaxation time (T2)-weighted magnetic resonance imaging were used to study the relationship between the duration of hypoxia-ischemia [unilateral common carotid artery (CCA) ligation and exposure to 8% oxygen] and the in vivo visualization of brain edema in 7-d-old rats. After CCA ligation, 35 animals were divided into five groups according to the length of exposure to 8% oxygen: no exposure (n = 9), 15 min (n = 12), 30 min (n = 5), and 1 h (n = 9) exposure; six animals served as controls. Diffusion weighted images were acquired 2 h after the hypoxic-ischemic insult, sequential T2 weighted images were recorded for up to 7 d and the outcome was documented by histologic examination at 21 d. The apparent diffusion coefficient of water in the ipsilateral cortex was significantly decreased in all animals recovering from prolonged hypoxic-ischemic insult (30 min and longer), whereas this was the case in only 40% of animals exposed to 15 min of hypoxia. Moreover, T2 prolongation of brain tissue occurred only in the former group. These results indicate transient and reversible alterations of physiologic water compartmentation for short term hypoxia-ischemia, but irreversible edema formation for long term hypoxia-ischemia. They support the hypothesis that the duration of hypoxia-ischemia determines whether a vasogenic edema and infarction follows the initial cytotoxic edema.

Changes of liver metabolite concentrations in adults with disorders of fructose metabolism after intravenous fructose by 31P magnetic resonance spectroscopy.

ABSTRACT: A novel 31P magnetic resonance spectroscopy procedure allows the estimation of absolute concentrations of certain phosphorus-containing compounds in liver. We have validated this approach by measuring ATP, phosphomonesters, and inorganic phosphate (Pi during fasting and after an i.v. fructose bolus in healthy adults and in three adults with disorders of fructose metabolism and by comparing results with known metabolite concentrations measured chemically. During fasting, the ATP concentration averaged 2.7 ± 0.3 (SD, n = 9) mmol/L, which, after due correction for other nucleoside triphosphates, was 2.1 mmol/L and corresponded well with known concentrations. Fructose-1-phosphate (F-1-P) could not be measured during fasting; its concentration after fructose was calculated from the difference of the phosphomonester signals before (2.9 ± 0.2 mmol/L) and after fructose. Pi was 1.4 ± 0.3 mmol/L and represented the one fourth of Pi visible in magnetic resonance spectra. In the three healthy controls after fructose (200 mg/kg, 20% solution, 2.5 min), the fructokinase-mediated increase of F-l-P was rapid, reaching 4.9 mmol/L within 3 min, whereas the uncorrected ATP decreased from 2.7 to 1.8 mmol/L and the Pi from 1.4 to 0.3 mmol/L. The subsequent decrease of F-l-P, mediated by fructaldolase, was accompanied by an overshooting rise of Pi to 2.7 mmol/L. In the patient with essential fructosuria, the concentrations of F-l-P, ATP, and Pi remained unchanged, confirming that fructokinase was indeed inactive. In the patient with hereditary fructose intolerance, initial metabolic changes were the same as in the controls, but baseline concentrations were not yet reestablished after 7 h, indicating weak fructaldolase activity. In the patient with fructose-1,6-diphosphatase deficiency, initial metabolic changes were the same as in the controls, but normalization was slightly delayed.