Investigation of in vivo measurement of cerebral cytochrome-c-oxidase redox changes using near-infrared spectroscopy in patients with orthostatic hypotension

We have previously used a continuous four wavelength near infrared spectrometer to measure changes in the cerebral concentrations of oxy- (Δ[HbO2] and deoxy- haemoglobin (Δ[HHb]) during head-up tilt in patients with primary autonomic failure. The measured changes in light attenuation also allow calculation of changes in the concentration of oxidised cytochrome c oxidase (Δ[oxCCO]), and this paper analyses the Δ[oxCCO] during the severe episodes of orthostatic hypotension produced by this experimental protocol. We studied 12 patients during a passive change in position from supine to a 60º head-up tilt. The challenge caused a reduction in mean blood pressure of 59.93 (±26.12) mmHg (Mean (±SD), p<0.0001), which was associated with a reduction in the total concentration of haemoglobin (Δ[HbT]= Δ[HbO2]+Δ[HHb]) of 5.02 (±3.81) μM (p<0.0001) and a reduction in the haemoglobin difference concentration (Δ[Hbdiff]= Δ[HbO2]-Δ[HHb]) of 14.4 (±6.73) μM (p<0.0001). We observed a wide range of responses in Δ[oxCCO]. 6 patients demonstrated a drop in Δ[oxCCO] (0.17 ±0.15μM ); 4 patients demonstrated no change (0.01 ±0.12 μM ) and 2 patients showed an increase in Δ[oxCCO] (0.21 ±0.01 μM ). Investigation of the association between the changes in concentrations of haemoglobin species and the Δ[oxCCO] for each patient show a range of relationships. This suggests that a simple mechanism for crosstalk, which might produce artefactual changes in [oxCCO], is not present between the haemoglobin and the oxCCO NIRS signals. Further investigation is required to determine the clinical significance of the changes in [oxCCO]

Non-invasive measurement of a metabolic marker of infant brain function

While near-infrared spectroscopy (NIRS) haemodynamic measures have proven to be vastly useful in investigating human brain development, the haemodynamic response function (HRF) in infants is not yet fully understood. NIRS measurements of the oxidation state of mitochondrial enzyme cytochrome-c-oxidase (oxCCO) have the potential to yield key information about cellular oxygen utilisation and therefore energy metabolism. We used a broadband NIRS system to measure changes in oxCCO, in addition to haemodynamic changes, during functional activation in a group of 33 typically developing infants aged between 4 and 6 months. The responses were recorded over the right temporal lobe while the infants were presented with engaging videos containing social content. A significant increase in oxCCO was found in response to the social stimuli, with maximum increase of 0.238 ± 0.13 μM. These results are the first reported significant change in oxCCO in response to stimulus-evoked activation in human infants and open new vistas for investigating human infant brain function and its energy metabolism

Measurement and data analysis techniques for the investigation of adult cerebral haemodynamics using near infrared spectroscopy

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Near infrared spectroscopic quantification of changes in the concentration of oxidized cytochrome oxidase in the healthy human brain during hypoxemia

The near infrared cytochrome c oxidase (CCO) signal has potential as a clinical marker of changes in mitochondrial oxygen utilization. We examine the CCO signal response to reduced oxygen delivery in the healthy human brain. We induced a reduction in arterial oxygen saturation from baseline levels to 80% in eight healthy adult humans, whilst minimising changes in end tidal carbon dioxide tension. We measured changes in the cerebral concentrations of oxidized CCO (Δ[oxCCO]), oxy-hemoglobin (Δ[HbO2]) and deoxy-hemoglobin (Δ[HHb]) using broadband near infrared spectroscopy (NIRS), and estimated changes in cerebral oxygen delivery (ecDO2) using pulse oximetry and transcranial Doppler ultrasonography. Results are presented as median (interquartile range). At the nadir of hypoxemia ecDO2 decreased by 9.2(5.4-12.1)% (p<0.0001), Δ[oxCCO] decreased by 0.24(0.06-0.28) micromoles/l (p<0.01), total hemoglobin concentration increased by 2.83(2.27-4.46) micromoles/l (p<0.0001) and change in haemoglobin difference concentration (Δ[Hbdiff]=Δ[HbO2]-Δ[HHb]) decreased by 12.72(11.32-16.84) micromoles/l (p<0.0001). Change in ecDO2 correlated with Δ[oxCCO] (r=0.78, p<0.001), but not with either change in total hemoglobin concentration or Δ[Hbdiff]. This is the first description of cerebral Δ[oxCCO] during hypoxemia in healthy adults. Studies are ongoing to investigate the clinical relevance of this signal in patients with traumatic brain injury

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 (O2Hb) 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 O2Hb 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

Investigation of depth dependent changes in cerebral haemodynamics during face perception in infants

Near-infrared spectroscopy has been used to record oxygenation changes in the visual cortex of 4 month old infants. Our in-house topography system, with 30 channels and 3 different source–detector separations, recorded changes in the concentration of oxy-, deoxy- and total haemoglobin (HbO2, HHb and HbT) in response to visual stimuli (face, scrambled visual noise and cartoons as rest). The aim of this work was to demonstrate the capability of the system to spatially localize functional activation and study the possibility of depth discrimination in the haemodynamic response. The group data show both face stimulation and visual noise stimulation induced significant increases in HbO2 from rest, but the increase in HbO2 with face stimulation was not significantly different from that seen with visual noise stimulation. The face stimuli induced increases in HbO2 were spread across a greater area across all depths than visual noise induced changes. In results from a single subject there was a significant increase of HbO2 in the inferior area of the visual cortex in response to both types of stimuli, and a larger number of channels (source–detector pairs) showed HbO2 increase to face stimuli, especially at the greatest depth. Activation maps were obtained using 3D reconstruction methods on multi source–detector separation optical topography data

Current and potential uses of composted olive oil waste

Food industry will have to focus on waste avoidance as well as utilisation of process waste. Application of clean technologies greatly enhances the safety and quality of the product as well as reducing the energy requirements and environmental impact of the food industry. The main environmental impacts of the food sector are aquatic, atmospheric and solid waste emissions. Nowadays, the main treatment method of solid wastes is composting, while recovery and reuse of by-products and wastes as raw materials stand for another effective option (http:// www.oulu.fi/resopt/wasmin/pap.pdf). Composted olive oil waste can find applications (1) as amendment in agriculture because of its high nitrogen and phosphorus content, (2) as a biofertiliser, with a mixture of compost with Sphagnum peat or commercial substrate finding use for ornamental plants growth and (3) as a biofilter for toxic metal removal. However, there are a number of disadvantages as well, such as large decline of soil germination capability, necrosis of the leaves and slow emission of secondary stems, and enhanced phytotoxicity, because of pH neutralisation technique, which should be seriously taken into account prior to opting for composting as a promising waste treatment alternative