Dt Delpy

Characterization of the near infrared absorption spectra of cytochrome aa3 and haemoglobin for the non-invasive monitoring of cerebral oxygenation

Near infrared (IR) spectroscopy can give continuous, direct information about cerebral oxygenation in vivo by providing signals from oxygenated and deoxygenated haemoglobin and cytochrome aa3. Due to a lack of precise spectral information and uncertainties about optical path length it has previously been impossible to quantify the data. We have therefore obtained the cytochrome aa3 spectrum in vivo from the brains of rats after replacing the blood with a fluorocarbon substitute. Near infrared haemoglobin spectra were also obtained, at various oxygenation levels, from cuvette studies of lysed human red blood cells. Estimates of optical path length have been obtained. The data were used to construct an algorithm for calculating the changes in oxygenated and deoxygenated haemoglobin and oxygenated cytochrome aa3 in tissue from changes in near IR absorption.

Prognosis of newborn infants with hypoxic-ischemic brain injury assessed by phosphorus magnetic resonance spectroscopy.

ABSTRACT: To investigate the prognostic significance of abnormalities of oxidative phosphorylation, the brains of 61 newborn infants born at 27-42 wk of gestation and suspected of hypoxic-ischemic brain injury were examined by surface-coil phosphorus magnetic resonance spectroscopy. Of these infants, 23 died, and the neurodevelopmental status of the 38 survivors was assessed at 1 y of age. Of the 28 infants whose phosphocreatine/inorganic orthophosphate (PCr/Pi) ratios fell below 95% confidence limits for normal infants, 19 died, and of the nine survivors, seven had serious multiple impairments (sensitivity 74%, specificity 92%, positive predictive value for unfavorable outcome 93%). Of the 12 infants with ATP/total phosphorus ratios below 95% confidence limits 11 died (sensitivity 47%, specificity 97%, positive predictive value 91%). Among the 46 infants with increased cerebral echodensities, PCr/Pi was more likely to be low, and prognosis poor, in infants whose echodensities were diffuse or indicated intraparenchymal hemorrhage than in infants whose echodensities were consistent with periventricular leukomalacia. We conclude that when reduced values for PCr/Pi indicating severely impaired oxidative phosphorylation are found in the brains of infants suspected of hypoxicischemic injury, the prognosis for survival without serious multiple impairments is very poor, and that when ATP/ total phosphorus is reduced, death is almost inevitable.

CEREBRAL ENERGY METABOLISM STUDIED WITH PHOSPHORUS NMR SPECTROSCOPY IN NORMAL AND BIRTH-ASPHYXIATED INFANTS

Phosphorus (31P) nuclear magnetic resonance spectroscopy was used to study intracellular metabolism in the brains of 6 normal newborn infants and 10 infants who had been asphyxiated during delivery. In the normal infants spectral peaks mainly attributable to adenosine triphosphate, phosphocreatine (PCr), phosphodiesters plus phospholipids, and inorganic orthophosphate (Pi) were always detected, together with an additional large peak in the phosphomonoester region indicating the presence of a metabolite or metabolites (probably largely phosphoethanolamine) which may be involved in rapid growth of the brain. In the asphyxiated infants, data obtained on the first day of life showed no differences from those in normal infants, but by the second to ninth days inverse changes in the concentrations of PCr and Pi had caused a significant reduction in PCr/Pi. This latency suggest the possibility of effective early treatment before irreversible metabolic damage sets in. Mean intracellular pH when PCr/Pi was minimal was 7.17 +/- 0.10. Values for PCr/Pi below 0.80 were associated with a very bad prognosis for survival and early neuro-developmental outcome.

Effects of indomethacin on cerebral haemodynamics in very preterm infants

Near infrared spectroscopy was used to investigate the effects of intravenously administered indomethacin (0.1-0.2 mg/kg) on cerebral haemodynamics and oxygen delivery in 13 very preterm infants treated for patent ductus arteriosus. 7 infants received indomethacin by rapid injection (30 s) and 6 by slow infusion (20-30 min). In all the infants cerebral blood flow, oxygen delivery, blood volume, and the reactivity of blood volume to changes in arterial carbon dioxide tension fell sharply after indomethacin. There were no differences in the effects of rapid and slow infusion. These falls in cerebral oxygen delivery and the disruption of cerebrovascular control might compromise cellular oxygen availability, particularly in regions of the brain where the arterial supply is precarious. Care should be taken to ensure that oxygen delivery is optimum before the administration of indomethacin to preterm infants.

Response of cerebral blood volume to changes in arterial carbon dioxide tension in preterm and term infants

ABSTRACT: The response of cerebral blood volume (CBVR) to a small induced change in arterial carbon dioxide tension was studied by near-infrared spectroscopy in 17 newborn infants born from 26 wk of gestation to term. All 17 infants were undergoing mechanical ventilation but had apparently normal brains. The CBVR per kPa change in arterial carbon dioxide tension within the range 3.9 to 9.6 kPa was calculated from the change in total cerebral Hb concentration ([TCHb]) using the equation: ΔCBV = Δ[TCHb] × 0.89/[H] where [H] is the large vessel Hb concentration. A least-squares regression line with 95% confidence limits was derived for CBVR against gestational age. A highly significant linear increase in CBVR was found: mean CBVR from the regression increased from 0.07 mL·100 g-1·kPa-1 at 26 wk to 0.51 mL·100 g-1·kPa-1 at 40 wk.

Synchronization between arterial blood pressure and cerebral oxyhaemoglobin concentration investigated by wavelet cross-correlation

Wavelet cross-correlation (WCC) is used to analyse the relationship between low-frequency oscillations in near-infrared spectroscopy (NIRS) measured cerebral oxyhaemoglobin (O(2)Hb) and mean arterial blood pressure (MAP) in patients suffering from autonomic failure and age-matched controls. Statistically significant differences are found in the wavelet scale of maximum cross-correlation upon posture change in patients, but not in controls. We propose that WCC analysis of the relationship between O(2)Hb and MAP provides a useful method of investigating the dynamics of cerebral autoregulation using the spontaneous low-frequency oscillations that are typically observed in both variables without having to make the assumption of stationarity of the time series. It is suggested that for a short-duration clinical test previous transfer-function-based approaches to analyse this relationship may suffer due to the inherent nonstationarity of low-frequency oscillations that are observed in the resting brain.

Oscillations in Cerebral Haemodynamics

The blood oxygenation level dependent (BOLD) contrast signal in functional magnetic resonance imaging (fMRI) provides highly spatially resolved deoxygenation maps of the activated cortex (Turner 1995). In common with many other activation measurement techniques, (including optical measurements) fMRI relies upon multiple repetition of the stimulus followed by signal averaging, baseline subtraction and extensive thresholding techniques to provide difference images of activation.

Measurement of Cerebral Blood Flow in Adult Humans Using Near Infrared Spectroscopy — Methodology and Possible Errors

The principle of near infrared spectroscopy (NIRS) was first clearly defined by Jobsis in 1977, and recent technical and methodological advances have made it possible to use NIRS to make non-invasive, quantitative measurements of tissue oxygenation and haemodynamics (Reynolds et al 1988). The NIRS technique has been applied predominantly to the measurement of neonatal cerebral haemodynamics (Brazy et al 1985, 1986, Ferrari et al 1986, Wyatt et al 1986, 1991); in particular the quantification of cerebral blood volume (Wyatt et al 1990) and blood flow (CBF)(Edwards et al 1988a).

Brain Metabolism and Intracellular pH During Ischaemia and Hypoxia: An In Vivo 31P and 1H Nuclear Magnetic Resonance Study in the Lamb

Abstract: Brain metabolism and intracellular pH were studied during and after episodes of ischaemia and hypoxia‐ischaemia in lambs anaesthetised with sodium pentobarbitone. 31P and 1H magnetic resonance spectroscopy methods were used to monitor brain pHi and brain concentrations of Pi, phosphocreatine (PCr), β‐nucleoside triphosphate (βNTP), and lactate. Simultaneous measurements were made of cerebral blood flow and cerebral oxygen and glucose consumption. Cerebral ischaemia sufficient to reduce oxygen delivery to 75% of control values was associated with a fall in brain pHi and increase in brain Pi. Progressively severe hypoxia‐ischaemia was associated with a progressive fall in brain pHi, PCr, and βNTP and increase in brain pi In two animals the increase in brain lactate during hypoxia‐ischaemia measured by 1H nuclear magnetic resonance (NMR) could be quantitatively accounted for by the increased net uptake of glucose by the brain in relation to oxygen, but was insufficient to account for the concomitant aci‐dosis according to previous estimates of brain buffering capacity. In four animals brain pHi, PCr, pi, and βNTP had returned to normal 1 h after the hypoxic‐ischaemic episode. In one animal brain pHi had reverted to normal at a time when 1H NMR indicated persistent elevation of brain lactate.

Phosphorus Metabolites and Intracellular pH in the Brains of Normal and Small for Gestational Age Infants Investigated by Magnetic Resonance Spectroscopy

ABSTRACT: The brains of 30 normal preterm and term infants whose birth wt were appropriate for gestational age and 13 who were small for gestational age but healthy were studied by phosphorus magnetic resonance spectroscopy to determine values for metabolite concentration ratios and intracellular pH. In the AGA infants, phosphocreatine/ inorganic orthophosphate increased between 28 and 42 wk of gestational plus postnatal age, suggesting a rise in the phosphorylation potential of brain tissue. At the same time, the concentration of phosphomonoester (mainly phosphoethanolamine) fell and that of phosphodiester (including phosphatidylethanolamine and phosphatidylcholine) increased. These changes reflected myelination and proliferation of membranes. Intracellular pH was ˜7.1 and did not change with brain maturation. No differences were detected in these variables between the infants who were small for gestational age and those who were appropriate for gestational age.