Ij Cox

Cerebral metabolism within 18 hours of birth asphyxia : A proton magnetic resonance spectroscopy study

Proton magnetic resonance spectroscopy (1H MRS) was performed within 18 h of birth (median 13, range 4-18 h) on 16 term infants with clinical features of birth asphyxia. Ten infants with no evidence of birth asphyxia were studied as controls at 5-18 (median 8) h after birth. To detect delayed impairments in cerebral energy metabolism, 15 infants suspected of asphyxia underwent 31P MRS at 33-106 (median 62) h of age. Choline, creatine, and N-acetylaspartate (NAA) were detected in spectra located to the basal ganglia in all infants. Lactate was detected in 15 of the 16 infants suspected of asphyxia, but in only 4 of the 10 controls (p < 0.05, χ2). Glutamine and glutamate (Glx) was detected in 11 infants suspected of asphyxia and in three controls, but this difference was not significant at the 5% level. The spectra revealed no other significant differences between asphyxiated infants and controls. In the asphyxiated infants, there was a negative correlation between the ratio of lactate to creatine in the first 18 h of life and phosphocreatine/inorganic phosphate(PCr/Pi) at 33-106 h (p < 0.001). Five severely asphyxiated infants had PCr/Pi < 0.75 (median 0.53, range 0.14-0.65), indicating a poor neurodevelopmental prognosis, and a further infant died before PCr/Pi could be measured. Ten infants had PCr/Pi > 0.75 (1.03, 0.76-1.49). Median lactate/creatine was 1.47(range 0.67-3.81) in the six severely affected subjects, 0.38 (0-1.51) in the latter group, and 0 (0-0.6) in controls (p < 0.0005, Kruskall-Wallis). These results suggest that, after birth asphyxia, cerebral energy metabolism is abnormal during the period when 31P MRS characteristically gives normal results. 1H MRS might be of value in predicting which infants are likely to suffer a decline in cerebral high energy phosphate concentrations and subsequent neurodevelopmental impairment.

The benefits of increasing spatial resolution as a means of reducing artifacts due to field inhomogeneities

All users of NMR equipment are familiar with the desirability of achieving as high a quality of field as possible. On the other hand, it is easy to forget that the field quality of relevance in both imaging and spectroscopy is that over individual voxels, and not the whole volume. This note demonstrates in practice how performance in poor fields is improved substantially by reducing voxel size (or increasing spatial resolution), offering a potential alternative to additional shimming under appropriate circumstances. It argues that the best criterion for assessing magnet quality in spatially localized systems is the maximum field error gradient in the volume of usable field, rather than the maximum deviation in the field.

Proton MR Spectroscopy of the Brain in AIDS Dementia Complex

Proton MR spectroscopy of the brain has been undertaken in 8 healthy volunteers and in 11 patients with human immunodeficiency virus infection and varying stages of AIDS dementia complex (ADC). Spectral appearances in patients with no ADC or early ADC were not significantly different from normal volunteers. Spectra from patients with moderate to severe ADC exhibited significant reductions in levels of N-acetyl aspartate (NAA) relative to creatine (Cr) and also showed elevations in choline containing compounds (relative to Cr). Because NAA is thought to be a metabolic marker for normally functioning neurons, these findings suggest the presence of neuronal injury or loss in moderate to severe ADC. The significance of these findings is discussed.

PROTON MR SPECTROSCOPY OF THE BRAIN IN INFANTS

Proton magnetic resonance spectroscopy (MRS) was used to study the brain of 2 normal and 15 abnormal infants aged from 33 weeks postmenstrual age (PMA) to 14 months postnatal age. Eleven of the infants were examined on at least two occasions. The principal clinical diagnoses in the abnormal infants were perinatal ischemic and hemorrhagic brain injury. All proton spectra demonstrated peaks that were assigned to N-acetylaspartate (NAA), choline containing compounds (Cho), and creatine plus phosphocreatine (Cr). The NAA/Cho and NAA/Cr ratios increased with age, while the Cho/Cr ratio decreased with age in the majority of infants. The NAA/Cho ratio was generally lower in abnormal infants, but the difference was not apparent before 40 weeks (PMA). This ratio was lowest in infants with the severest degree of neurological abnormality. Proton and phosphorus MRS was compared in seven infants. In those with severe brain lesions, early phosphorus spectra were abnormal. On follow-up the phosphorus spectra became normal, but the proton spectra showed persistently low NAA/Cho and NAA/Cr ratios. Proton MRS provides new information that may be complementary to phosphorus MRS in the diagnosis and monitoring of brain development in normal and neurologically damaged infants.

PROTON SPECTROSCOPY OF THE NEONATAL BRAIN FOLLOWING HYPOXIC-ISCHAEMIC INJURY

Proton magnctic resonance spectroscopy was used to examine. within the first month of life, the brains of 11 infants born at term—10 with signs of hypoxic‐ischaernic encephalopathy (HIE) and one who was neurologically normal at birth. All the infants had peak resonances on their spectra which could be assigned to N‐acetylaspartase (NAA). choline‐containing compounds (Cho) and creatine plus phosphocreatine (Cr). When neurodevelopmental outcome at one year was correlated with initial spectroscopy findings, the NAA/Cho and NAA/Cr ratios reflected clinical outcome. This study suggests that proton spcctroxopy not only provides new information about biochemical changes occurring in the brains of infants with HIE, but also may help to predict outcomc within the first month of life.

Persistent increases in cerebral lactate concentration after birth asphyxia

In this prospective study proton magnetic resonance spectroscopy(1H MRS) was used to test the hypothesis that lactate can be detected later than 1 mo after birth in the brains of infants who display severe neurodevelopmental impairment 1 y after transient perinatal hypoxia-ischemia. Data were obtained from three groups of infants:1) eight infants suffering birth asphyxia followed by perinatal encephalopathy and abnormal neurodevelopmental outcome at 1 y of age (defined as major neurologic impairment, Griffiths quotient <85%, and low optimality score); 2) 10 infants with signs of perinatal hypoxia-ischemia but normal neurodevelopmental outcome at 1 y; and 3) six control infants with uneventful perinatal courses and normal neurodevelopment at 1 y. Between one and four examinations (median 1) were performed at median (range) 11 (4-68) wk after birth, and the cerebral concentration ratio of lactate to creatine plus phosphocreatine (Cr) calculated from each spectrum. Lactate was detected later than the 1st mo after birth in seven of eight infants with abnormal neurodevelopmental outcome [maximum detected lactate/Cr was median (range) 0.44 (0.24-0.67)]. No lactate was detected later than the 1st mo after birth in infants with normal neurodevelopmental outcome, nor in five of six control subjects, although a small amount of lactate was detected in one control infant (lactate/Cr = 0.04). These results suggest that the pathologic postasphyxial process, indicated by persistent cerebral lactate, may not be confined to the period immediately after injury.

Cerebral intracellular lactic alkalosis persisting months after neonatal encephalopathy measured by magnetic resonance spectroscopy.

We have found that cerebral lactate can be detected later than 1 month of age after neonatal encephalopathy (NE) in infants with severe neurodevelopmental impairment at 1 y. Our hypothesis was that persisting lactate after NE is associated with alkalosis and a decreased cell phosphorylation potential. Forty-three infants with NE underwent proton and phosphorus-31 magnetic resonance spectroscopy at 0.2-56 wk postnatal age. Seventy-seven examinations were obtained: 25 aged <2 wk, 16 aged ≥ 2 to ≤ 4 wk, 25 aged >4 to ≤ 30 wk, and 11 aged >30 wk. Neurodevelopmental outcome was assessed at 1 y of age: 17 infants had a normal outcome and 26 infants had an abnormal outcome. Using univariate linear regression, we determined that increased lactate/creatine plus phosphocreatine (Cr) was associated with an alkaline intracellular pH (pHi) (p < 0.001) and increased inorganic phosphate/phosphocreatine (Pi/PCr) (p < 0.001). This relationship was significant, irrespective of outcome group or age at time of study. Between outcome groups, there were significant differences for lactate/Cr measured at <2 wk (p = 0.005) and >4 to ≤ 30 wk (p = 0.01); Pi/PCr measured at <2 wk (p < 0.001); pHi measured at <2 wk (p < 0.001), ≥ 2 to ≤ 4 wk (p = 0.02) and >4 to ≤ 30 wk (p = 0.03); and for N-acetylaspartate/Cr measured at ≥ 2 to ≤ 4 wk (p = 0.03) and >4 to ≤ 30 wk (p = 0.01). Possible mechanisms leading to this persisting cerebral lactic alkalosis are a prolonged change in redox state within neuronal cells, the presence of phagocytic cells, the proliferation of glial cells, or altered buffering mechanisms. These findings may have implications for therapeutic intervention.

Proton MR spectroscopy in herpes simplex encephalitis: assessment of neuronal loss.

We present here the case of an 11-year-old boy with herpes simplex encephalitis diagnosed on the basis of clinical features, serology, and response to acyclovir, who relapsed after 3 weeks of therapy. In vivo proton magnetic resonance spectroscopy (1H MRS) of the brain, at 8 and 16 weeks after the onset of symptoms, showed abnormalities, most prominently a reduction in the N-acetylaspartate/choline ratio. The role of 1H MRS in assessing disease activity is discussed.

Early Increases in Brain myo -Inositol Measured by Proton Magnetic Resonance Spectroscopy in Term Infants with Neonatal Encephalopathy

Our aim was to assess brain myo-inositol/creatine plus phosphocreatine (Cr) in the first week in term infants with neonatal encephalopathy using localized short echo time proton magnetic resonance spectroscopy and to relate this to measures of brain injury, specifically lactate/Cr in the first week, basal ganglia changes on magnetic resonance imaging (MRI), and neurodevelopmental outcome at 1 y. Fourteen term infants with neonatal encephalopathy of gestational age (mean ± SD) 39.6 ± 1.6 wk, birth weight 3270 ± 490 g, underwent MRI and magnetic resonance spectroscopy at 3.5 ± 2.1 d. Five infants were entered in a pilot study of treatment with moderate whole-body hypothermia for neonatal encephalopathy; two were being cooled at the time of the scan. T1- and T2-weighted transverse magnetic resonance images were graded as normal or abnormal according to the presence or absence of the normal signal intensity of the posterior limb of the internal capsule and signal intensity changes in the basal ganglia. Localized proton magnetic resonance spectroscopy data were obtained from an 8-cm3 voxel in the basal ganglia using echo times of 40 and 270 ms, and the peak area ratios of myo-inositol/Cr and lactate/Cr were measured. Outcome was scored using Griffiths development scales and neurodevelopmental examination at 1 y. MRI and outcome were normal in six infants and abnormal in eight. myo-Inositol/Cr and lactate/Cr were higher in infants with abnormal MRI and outcome (p < 0.01, p < 0.01, respectively). myo-Inositol/Cr and lactate/Cr were correlated (p < 0.01) and were both correlated to the Griffiths developmental scales (p < 0.01, p < 0.01, respectively). In conclusion, these preliminary data suggest that early increases in brain basal ganglia myo-inositol/Cr in infants with neonatal encephalopathy are associated with increased lactate/Cr, MRI changes of severe injury, and a poor neurodevelopmental outcome at 1 y.

Evidence for altered hepatic gluconeogenesis in patients with cirrhosis using in vivo 31-phosphorus magnetic resonance spectroscopy

BACKGROUND AND AIMS Alterations in gluconeogenesis in the diseased liver can be assessed non-invasively using magnetic resonance spectroscopy by measuring changes in phosphomonoester resonance which contains information regarding several metabolites, including the phosphorylated intermediates of the gluconeogenic pathway. METHODS 31P magnetic resonance spectroscopy was used to determine changes in phosphomonoesters following bolus infusions of 2.8 mmol/kgl-alanine in five patients with functionally compensated cirrhosis and in five patients with functionally decompensated cirrhosis. RESULTS Compared with six healthy volunteers, baseline phosphomonoester values were elevated by 35% (p<0.05) in the compensated cirrhosis group and by 57% (p<0.01) in the decompensated cirrhosis group. Following alanine infusion, phosphomonoesters in healthy volunteers increased by 46% from baseline values (p<0.01), in patients with compensated cirrhosis by 27% (p<0.02) but those with decompensated cirrhosis showed no increase from baseline. There was a reduction in the percentage of inorganic phosphate signal in all subjects. CONCLUSIONS By analysing changes in phosphomonoester and inorganic phosphate resonances it is possible to discern clear metabolic differences between healthy volunteers and patients with cirrhosis of varying severity using magnetic resonance spectroscopy. Those patients with functionally decompensated cirrhosis have higher percentage baseline phosphomonoester values but the absence of phosphomonoester elevation following l-alanine infusion suggests that they are unable to mount a significant metabolic response with a progluconeogenic stimulus.