Neuronal activation induced changes in microcirculatory haemoglobin oxygenation: to dip or not to dip (original) (raw)
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Journal of Clinical Monitoring, 1992
Rampil IJ, Litt L, Mayevsky A. Correlated, simultaneous, multiplewavelength optical monitoring in vivo of localized cerebrocortical NADH and brain microvessel hemoglobin oxygen saturation. J Clin Monit 1992;8:216-225 ABSTRACT. Current forms of brain monitoring, such as electroencephalography (EEG), have had limited clinical utility. The EEG records spontaneous cerebrocortical activity and thus is an indirect indicator of metabolic demand and, to a lesser extent, an indicator of mismatch of supply versus demand. Ischemia modulates EEG activity in ways that can usually be detected, but EEG patterns can be similarly modulated by many other factors, including temperature and pharmacologic manipulation. This in vivo study in physiologically monitored animals evaluated the use of correlated optical spectroscopy, performed with an instrument having a fiberoptic light-guide bundle in contact with the cerebral cortex, for the simultaneous monitoring of cerebrovascular oxygen availabihty and intracellular oxygen delivery. A highly specific monitor of cerebral intracellular oxygen supply, the cerebrocortical intramitochondrial N A D H redox state, was monitored in vivo with a fluorescence technique. Absorption spectroscopy was used concurrently to monitor hemoglobin content (blood volume) and oxygen saturation in the microcirculation. Correlated changes in optical signals from cerebrocortical N A D H and hemoglobin were studied in a swine model (n = 7) of nitrogen hypoxia. Measurements were made at four wavelengths with a time-division, multiplexed fluorometer/reflectometer. Because the N A D H fluorescence signal at 450 nm is affected by local changes in blood volume, a "corrected" fluorescence signal is usually calculated, In previous studies, where only two wave lengths have been measured, attempts at correction were based on reflectance at the excitation wavelength (366 nm). We compared estimators of changes in microcirculatory blood volume using reflection at two wavelengths: 366 nm and 585 nm, the wavelengths for maximum and isobestic absorption. The results of the studies were as follows: (1) during transient hypoxia, N A D H and local hemoglobin saturation signals changed in concert with arterial pulse oximetry, with changes in N A D H lagging behind changes in saturation by an average of 5.3 seconds;
Neuron, 2004
hemodynamic changes is required for interpreting perfusion-based functional imaging results as indicative of at the University of California, Los Angeles Los Angeles, California 90024 actual brain activity. Recent studies have arrived at differing conclusions regarding the linearity (Logothetis et al., 2001) or nonlinearity (Devor et al., 2003) of coupling between neuronal activity and hemodynamic re-Summary sponses.
Spectroscopic analysis of neural activity in brain: increased oxygen consumption following …
Neuroimage, 2000
This research investigates the hemodynamic response to stimulation of the barrel cortex in anaesthetized rats using optical imaging and spectroscopy . A slit spectrograph was used to collect spectral image data sequences. These were analyzed using an algorithm that corrects for the wavelength dependency in the optical path lengths produced by the light scattering properties of tissue. The analysis produced the changes in the oxyand deoxygenation of hemoglobin following stimulation. Two methods of stimulation were used. One method mechanically vibrated a single whisker, the other electrically stimulated the whisker pad. The electrical stimulation intensity varied from 0.4 to 1.6 mA. The hemodynamic responses to stimulation increased as a function of intensity. At 0.4 mA they were commensurate with those from the mechanical stimulation; however, the responses at the higher levels were greater by a factor of ϳ10. For both methods of data collection, the results of the spectroscopic analysis showed an early increase in deoxygenated hemoglobin (Hbr) with no evidence for a corresponding decrease in oxygenated hemoglobin (HbO 2 ). Evidence for increased oxygen consumption (CMRO 2 ) was obtained by converting the fractional changes in blood volume (Hbt) into estimates of changes in blood flow and using the resulting time course to scale the fractional changes in Hbr. The results show an early increase CMRO 2 peaking ϳ2 s after stimulation onset. Using these methods, we find evidence for increased oxygen consumption following increased neural activity even at low levels of stimulation intensity.
Biophysical Journal, 1997
A newly developed microscope using acousto-optic tunable filters (AOTFs) was used to generate in vivo hemoglobin saturation (SO2) and oxygen tension (PO2) maps in the cerebral cortex of mice. S02 maps were generated from the spectral analysis of reflected absorbance images collected at different wavelengths, and P02 maps were generated from the phosphorescence lifetimes of an injected palladium-porphyrin compound using a frequency-domain measurement. As the inspiratory°2 was stepped from hypoxia (10% 02), through normoxia (21 % 02), to hyperoxia (60% 02), measured S02 and PO2 levels rose accordingly and predictably throughout. A plot of S02 versus P02 in different arterial and venous regions of the pial vessels conformed to the sigmoidal shape of the oxygen-hemoglobin dissociation curve, providing further validation of the twp mapping procedures. The study demonstrates the versatility of the AOTF microscope for in vivo physiologic investigation, allowing for the generation of nearly simultaneous S02 and P02 maps in the cerebral cortex, and the frequency-domain detection of phosphorescence lifetimes. This class of study opens up exciting new possibilities for investigating the dynamics of hemoglobin and°2 binding during functional activation of neuronal tissues.
Journal of Cerebral Blood Flow & Metabolism, 1987
A simple method was developed to measure in vivo local oxygen consumption quantitatively in the brain cortex. Reflectance spectra of tissue hemoglobin at the brain's surface were measured for assessment of both local tissue hemoglobin content and its oxygen saturation. Local oxygen consumption was calculated from the spectral changes of tissue hemoglobin during complete cessation of blood flow by compression of the cortical surface in the suprasylvian gyrus with the tip of an optic probe. This procedure was performed without any brain damage and only took ∼5 s. The calculated local oxygen consumption during this short period of compression remained constant for a few seconds. Then, it decreased rapidly, although the local tissue hemoglobin was not completely deoxygenated. The value of local cerebral oxygen consumption obtained by this method was 3.02 ± 0.61 mL O2/100 g brain/min; it was not influenced by the change in systemic blood pressure. The effect of pentobarbital on cereb...
Optics Letters, 2003
A simple instrument is demonstrated for high-resolution simultaneous imaging of total hemoglobin concentration and oxygenation and blood f low in the brain by combining rapid multiwavelength imaging with laser speckle contrast imaging. The instrument was used to image changes in oxyhemoglobin and deoxyhemoglobin and blood f low during cortical spreading depression and single whisker stimulation in rats through a thinned skull. The ability to image blood f low and hemoglobin concentration changes simultaneously with high resolution will permit detailed quantitative analysis of the spatiotemporal hemodynamics of functional brain activation, including imaging of oxygen metabolism. This is of significance to the neuroscience community and will lead to a better understanding of the interrelationship of neural, metabolic, and hemodynamic processes in normal and diseased brains.
NeuroImage, 2001
Optical imaging spectroscopy (OIS) and laser Doppler flowmetry (LDF) data sequences from anesthetized rats were used to determine the relationship between changes in oxy-and deoxygenated hemoglobin concentration and changes in blood volume and flow in the presence and absence of stimulation. The data from Jones et al. (accompanying paper) were used to explore the differences between two theoretical models of flow activation coupling. The essential difference between the two models is the extension of the model of Buxton and Frank by Hyder et al. (1998, J. Appl. Physiol. 85: 554 -564) to incorporate change in capillary diffusivity coupled to flow. In both models activation-increased flow changes increase oxygen transport from the capillary; however, in Hyder et al.'s model the diffusivity of the capillary itself is increased. Hyder et al. proposed a parameter (⍀), a scaling "constant" linking increased blood flow and oxygen "diffusivity" in the capillary bed. Thus, in Buxton and Frank's theory, ⍀ ؍ 0; i.e., there are no changes in diffusivity. In Hyder et al.'s theory, 0 < ⍀ < 1, and changes in diffusivity are assumed to be linearly related to flow changes. We elaborate the theoretical position of both models to show that, in principle, the different predictions from the two theories can be evaluated using optical imaging spectroscopy data. We find that both theoretical positions have limitations when applied to data from brief stimulation and when applied to data from mild hypercapnia. In summary, the analysis showed that although Hyder et al.'s proposal that diffusivity increased during activation did occur; it was shown to arise from an implementation of Buxton and Frank's theory under episodes of brief stimulation. The results also showed that the scaling parameter ⍀ is not a constant as the Hyder et al. model entails but in fact varies over the time course of the flow changes. Data from experiments in which mild hypercapnia was administered also indicated changes in the diffusivity of the capillary bed, but in this case the changes were negative; i.e., oxygen transport from the capillary decreased relative to baseline under hypercapnia. Neither of the models could account for the differences between the hypercapnia and activation data when matched for equivalent flow changes. A modification to the models to allow non-null tissue oxygen concentrations that can be moderated by changes due to increased metabolic demand following increased neural activity is proposed. This modification would allow modulation of oxygen transport from the capillary bed (e.g., changes in diffusivity) by tissue oxygen tension and would allow a degree of decoupling of flow and oxygen delivery, which can encompass both the data from stimulation and from hypercapnia.
Advances in experimental medicine and biology, 2008
It has been suggested that changes in oxidised cytochrome c oxidase concentration ([oxCCO]) measured using cerebral near infrared spectroscopy (NIRS) may be algorithm artefacts. We examine the change in near infrared (NIR) attenuation by the healthy adult brain (n = 10) during hypoxaemia. Broadband spectroscopic data were collected during normoxia, and hypoxaemia. The UCLn algorithm was used to fit (a) oxy- (HbO2) and deoxy-haemoglobin (HHb) spectra (2 component fit), and (b) HbO2, HHb and oxidised-reduced cytochrome c oxidase difference spectra (3 component fit) to the mean change in NIR attenuation between baseline and hypoxaemia. The sum of squares of the residuals was 100 x 10(-7) OD2 for the 2 component fit and 8 x 10(-7) OD2 for the 3 component fit, and the two sets of residuals differed from each other (p = 0.0003). We compare experimental and simulated data and suggest that the 2 component residuals indicate a change in [oxCCO]. Changes in near infrared attenuation by the he...