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

Department of Medical Physics and Bioengineering, Malet Place Engineering Building, University College London, Gower Street, London, UK.
Physiological Measurement (Impact Factor: 1.81). 03/2007; 28(2):199-211. DOI: 10.1088/0967-3334/28/2/008
Source: PubMed


We have previously used a continuous four-wavelength near-infrared spectrometer to measure changes in the cerebral concentrations of oxy-haemoglobin (Delta[HbO(2)] and deoxy-haemoglobin (Delta[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 oxidized cytochrome-c-oxidase (Delta[(ox)CCO]), and this paper analyses the Delta[(ox)CCO] 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 60 degrees 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 (Delta[HbT] = Delta[HbO(2)] + Delta[HHb]) of 5.02 (+/-3.81) microM (p < 0.0001) and a reduction in the haemoglobin difference concentration (Delta[Hb(diff)] = Delta[HbO(2)] - Delta[HHb]) of 14.4 (+/-6.73) microM (p < 0.0001). We observed a wide range of responses in Delta[(ox)CCO]. Six patients demonstrated a drop in Delta[(ox)CCO] (0.17 +/- 0.15 microM); four patients demonstrated no change (0.01 +/- 0.12 microM) and two patients showed an increase in Delta[(ox)CCO] (0.21 +/- 0.01 microM). Investigation of the association between the changes in concentrations of haemoglobin species and the Delta[(ox)CCO] for each patient show a range of relationships. This suggests that a simple mechanism for crosstalk, which might produce artefactual changes in [(ox)CCO], is not present between the haemoglobin and the (ox)CCO NIRS signals. Further investigation is required to determine the clinical significance of the changes in [(ox)CCO].

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Available from: Terence S Leung, Oct 10, 2015
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    • "Possible interference of changes in optical scattering with the NIRS measurements [5,6] and insufficient separation of the chromophores by the algorithm used to convert optical density into changes in chromophore concentration [5,6,10–13] are the most frequently mentioned confounding effects. Despite these issues, several studies have reported Δ[oxCCO] measurements in the adult brain in a variety of settings, including visual stimulation [12,14], traumatic brain injury [15], manipulation of cerebral oxygen delivery [16,17], orthostatic hypotension [18], cardiopulmonary bypass during cardiac surgery [19] and obstructive sleep apnoea [20]. "
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    ABSTRACT: Using transcranial near-infrared spectroscopy (NIRS) to measure changes in the redox state of cerebral cytochrome c oxidase (Δ[oxCCO]) during functional activation in healthy adults is hampered by instrumentation and algorithm issues. This study reports the Δ[oxCCO] response measured in such a setting and investigates possible confounders of this measurement. Continuous frontal lobe NIRS measurements were collected from 11 healthy volunteers during a 6-minute anagram-solving task, using a hybrid optical spectrometer (pHOS) that combines multi-distance frequency and broadband components. Only data sets showing a hemodynamic response consistent with functional activation were interrogated for a Δ[oxCCO] response. Simultaneous systemic monitoring data were also available. Possible influences on the Δ[oxCCO] response were systematically investigated and there was no effect of: 1) wavelength range chosen for fitting the measured attenuation spectra; 2) constant or measured, with the pHOS in real-time, differential pathlength factor; 3) systemic hemodynamic changes during functional activation; 4) changes in optical scattering during functional activation. The Δ[oxCCO] response measured in the presence of functional activation was heterogeneous, with the majority of subjects showing significant increase in oxidation, but others having a decrease. We conclude that the heterogeneity in the Δ[oxCCO] response is physiological and not induced by confounding factors in the measurements.
    Biomedical Optics Express 10/2012; 3(10):2550-66. DOI:10.1364/BOE.3.002550 · 3.65 Impact Factor
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    • "Using a four-channel continuous-wave near-infrared spectroscope (Oxymon M III, Artinis Medical Systems, BV, The Netherlands), O 2 Hb and HHb were determined by measuring light attenuation at 760 and 864 nm wavelengths that was analyzed using algorithms based on the modified Beer–Lambert law. Detailed descriptions of NIRS methodology are described elsewhere (van der Sluijs et al., 1997; Grassi et al., 1999; Kirkpatrick et al., 1998; Tachtsidis et al., 2007). Two variables were calculated from O 2 Hb, and HHb: (1) tHb = O 2 Hb + HHb, and (2) the difference between changes of O 2 Hb and HHb concentrations (Hb diff ) = O 2 Hb − HHb. "
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    Antenna Theory and Techniques, 2003. 4th International Conference on; 10/2003
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