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]

A Hybrid Multi-Distance Phase and Broadband Spatially Resolved Spectrometer and Algorithm for Resolving Absolute Concentrations of Chromophores in the Near-Infrared Light Spectrum

For resolving absolute concentration of tissue chromophores in the human adult brain with near-infrared spectroscopy it is necessary to calculate the light scattering and absorption, at multiple wavelengths with some depth resolution. To achieve this we propose an instrumentation configuration that combines multi-distance frequency and broadband spectrometers to quantify chromophores in turbid media by using a hybrid spatially resolved algorithm. Preliminary results in solid phantoms as well as liquid dynamic homogeneous and inhomogeneous phantoms and in-vivo muscle measurements showed encouraging results

Analysis of the Changes in the Oxidation of Brain Tissue Cytochrome-c-Oxidase in Traumatic Brain Injury Patients during Hypercapnoea A Broadband NIRS Study

Using broadband near-infrared spectroscopy (NIRS) and cerebral micro-dialysis (MD), we investigated cerebral cellular metabolism and mitochondrial redox states, following hypercapnoea in 6 patients with traumatic brain injury (TBI). In all patients hypercapnoea increased intracranial pressure and cerebral blood flow velocity measured with transcranial Doppler. Despite the likely increase in cerebral oxygen delivery, we did not see an increase in the oxidation status of cytochrome-c-oxidase [oxCCO] in every patient. Analysis of the NIRS data demonstrated two patterns of the changes; Group A (n = 4) showed an increase in [oxCCO] of 0.34(+/-0.34)mu M and Group B (n = 2) a decrease of 0.40(+/- 0.41)mu M. Although no obvious association was seen between the Delta[oxCCO] and the MD, measured changes in lactate and pyruvate concentrations. Further work using model informed data interpretation may be helpful in understanding the multimodal signals acquired in this heterogeneous patient group

Adaptive Normalization in Streaming Data

In todays digital era, data are everywhere from Internet of Things to health care or financial applications. This leads to potentially unbounded ever-growing Big data streams and it needs to be utilized effectively. Data normalization is an important preprocessing technique for data analytics. It helps prevent mismodeling and reduce the complexity inherent in the data especially for data integrated from multiple sources and contexts. Normalization of Big Data stream is challenging because of evolving inconsistencies, time and memory constraints, and non-availability of whole data beforehand. This paper proposes a distributed approach to adaptive normalization for Big data stream. Using sliding windows of fixed size, it provides a simple mechanism to adapt the statistics for normalizing changing data in each window. Implemented on Apache Storm, a distributed real-time stream data framework, our approach exploits distributed data processing for efficient normalization. Unlike other existing adaptive approaches that normalize data for a specific use (e.g., classification), ours does not. Moreover, our adaptive mechanism allows flexible controls, via user-specified thresholds, for normalization tradeoffs between time and precision. The paper illustrates our proposed approach along with a few other techniques and experiments on both synthesized and real-world data. The normalized data obtained from our proposed approach, on 160,000 instances of data stream, improves over the baseline by 89% with 0.0041 root-mean-square error compared with the actual data

Modelling confounding effects from extracerebral contamination and systemic factors on functional near-infrared spectroscopy

Haemodynamics-based neuroimaging is widely used to study brain function. Regional blood flow changes characteristic of neurovascular coupling provide an important marker of neuronal activation. However, changes in systemic physiological parameters such as blood pressure and concentration of CO2 can also affect regional blood flow and may confound haemodynamics-based neuroimaging. Measurements with functional near-infrared spectroscopy (fNIRS) may additionally be confounded by blood flow and oxygenation changes in extracerebral tissue layers. Here we investigate these confounds using an extended version of an existing computational model of cerebral physiology, 'BrainSignals'. Our results show that confounding from systemic physiological factors is able to produce misleading haemodynamic responses in both positive and negative directions. By applying the model to data from previous fNIRS studies, we demonstrate that such potentially deceptive responses can indeed occur in at least some experimental scenarios. It is therefore important to record the major potential confounders in the course of fNIRS experiments. Our model may then allow the observed behaviour to be attributed among the potential causes and hence reduce identification errors

Theoretical investigation of measuring cerebral blood flow in the adult human head using bolus Indocyanine Green injection and near-infrared spectroscopy

To investigate the accuracy of measuring cerebral blood flow (CBF) using a bolus injection of Indocyanine Green (ICG) detected by near-infrared spectroscopy in adult human heads, simulations were performed using a two-layered model representing the extracerebral and intracerebral layers. Modeled optical data were converted into tissue ICG concentration using either the one-detector modified Beer-Lambert law (MBLL) method, or the two-detector partial path-length (PPL) method. The CBFs were estimated using deconvolution and blood flow index techniques. Using the MBLL method, the CBFs were significantly underestimated but the PPL method improved their accuracy and robustness, especially when used as relative measures. The dispersion of the arterial input function also affected the CBF estimates. (c) 2007 Optical Society of America

Hyperoxia results in increased aerobic metabolism following acute brain injury

Acute brain injury is associated with depressed aerobic metabolism. Below a critical mitochondrial pO2 cytochrome c oxidase, the terminal electron acceptor in the mitochondrial respiratory chain, fails to sustain oxidative phosphorylation. After acute brain injury, this ischaemic threshold might be shifted into apparently normal levels of tissue oxygenation. We investigated the oxygen dependency of aerobic metabolism in 16 acutely brain-injured patients using a 120-min normobaric hyperoxia challenge in the acute phase (24–72 h) post-injury and multimodal neuromonitoring, including transcranial Doppler ultrasound-measured cerebral blood flow velocity, cerebral microdialysis-derived lactate-pyruvate ratio (LPR), brain tissue pO2 (pbrO2), and tissue oxygenation index and cytochrome c oxidase oxidation state (oxCCO) measured using broadband spectroscopy. Increased inspired oxygen resulted in increased pbrO2 [ΔpbrO2 30.9 mmHg p < 0.001], reduced LPR [ΔLPR −3.07 p = 0.015], and increased cytochrome c oxidase (CCO) oxidation (Δ[oxCCO] + 0.32 µM p < 0.001) which persisted on return-to-baseline (Δ[oxCCO] + 0.22 µM, p < 0.01), accompanied by a 7.5% increase in estimated cerebral metabolic rate for oxygen (p = 0.038). Our results are consistent with an improvement in cellular redox state, suggesting oxygen-limited metabolism above recognised ischaemic pbrO2 thresholds. Diffusion limitation or mitochondrial inhibition might explain these findings. Further investigation is warranted to establish optimal oxygenation to sustain aerobic metabolism after acute brain injury