Evolution of the dynamic changes in functional cerebral oxidative metabolism from tissue mitochondria to blood oxygen (original) (raw)
Related papers
Journal of Cerebral Blood Flow & Metabolism, 2009
The possible role of oxygen metabolism in supporting brain activation remains elusive. We have used a newly developed neuroimaging approach based on high-field in vivo 17 O magnetic resonance spectroscopic (MRS) imaging to noninvasively image cerebral metabolic rate of oxygen (CMRO 2 ) consumption in cats at rest and during visual stimulation. It was found that CMRO 2 increases significantly (32.3%±10.8%, n = 6) in the activated visual cortical region as depicted in blood oxygenation level dependence functional maps; this increase is also accompanied by a CMRO 2 decrease in surrounding cortical regions, resulting a smaller increase (9.7%±1.9%) of total CMRO 2 change over a larger cortical region displaying either a positive or negative CMRO 2 alteration. Moreover, a negative correlation between stimulus-evoked percent CMRO 2 increase and resting CMRO 2 was observed, indicating an essential impact of resting brain metabolic activity level on stimulus-evoked percent CMRO 2 change and neuroimaging signals. These findings provide new insights into the critical roles of oxidative metabolism in supporting brain activation and function. They also suggest that in vivo 17 O MRS imaging should provide a sensitive neuroimaging modality for mapping CMRO 2 and its change induced by brain physiology and/or pathologic alteration. Keywords brain activation; cerebral metabolic rate of oxygen; functional MRI; in vivo 17 O MRS; imaging CMRO 2
Journal of Cerebral Blood Flow & Metabolism, 2001
Changes in cerebral blood flow (CBF) using laser-Doppler and microvascular O 2 oxygen tension using oxygendependent phosphorescence quenching in the rat somatosensory cortex were obtained during electrical forepaw stimulation. The signal-averaged CBF response resulting from electrical forepaw stimulation consisted of an initial peak (t ס 3.1 ± 0.8 seconds after onset of stimulation), followed by a plateau phase that was maintained throughout the length of the stimulus. In contrast, microvascular O 2 tension changes were delayed, reached a plateau level (t ס 23.5 ± 1.7 seconds after the onset of stimulation) that remained for the length of the stimulus and for several seconds after stimulus termination, and then returned to baseline. Using Fick's equation and these dynamic measurements, changes in the calculated cerebral metabolic rate of oxygen (CMRO 2 ) during functional stimulation were determined. The calculated CMRO 2 response initially was comparable with the CBF, but with protracted stimulation, CMRO 2 changes were approximately one-third that of CBF changes. These results suggest that a complex relation exists, with comparable changes in CBF and CMRO 2 initially occurring after stimulation but excessive changes in CBF compared with CMRO 2 arising with protracted stimulation. Key Words: Cerebral blood flow-Cerebral metabolic rate of O 2 -Oxygendependent phosphorescence quenching.
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.
Frontiers in neuroenergetics, 2010
Functional magnetic resonance imaging is widely used to map patterns of brain activation based on blood oxygenation level dependent (BOLD) signal changes associated with changes in neural activity. However, because oxygenation changes depend on the relative changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO(2)), a quantitative interpretation of BOLD signals, and also other functional neuroimaging signals related to blood or tissue oxygenation, is fundamentally limited until we better understand brain oxygen metabolism and how it is related to blood flow. However, the positive side of the complexity of oxygenation signals is that when combined with dynamic CBF measurements they potentially provide the best tool currently available for investigating the dynamics of CMRO(2). This review focuses on the problem of interpreting oxygenation-based signals, the challenges involved in measuring CMRO(2) in general, and what is needed to put oxygenation-based estim...
NeuroImage, 2005
The spatial extent of the changes in oxy-hemoglobin (HbO), deoxyhemoglobin (HbR), total hemoglobin concentration (HbT), cerebral blood flow (CBF), and the cerebral metabolic rate of oxygen (CMRO 2 ) in response to forepaw and whisker stimulation were compared in the rat somatosensory cortex using a combination of multi-wavelength reflectance imaging and laser speckle contrast imaging of cerebral blood flow. The spatial extents of the response of each hemodynamic parameter and CMRO 2 were found to be comparable at the time of peak response, and at early times following stimulation onset, the spatial extent of the change in HbR was smaller than that of HbO, HbT, CBF, and CMRO 2 . In addition, a slight spatial dependence was found in the power law coefficient relating changes in CBF and HbT. Although the CMRO 2 response is a metabolic measure and thus expected to have a more localized response than the hemodynamic parameters, the results presented here suggest that this may not be the case in general, possibly due to the increased sensitivity of optical imaging techniques to superficial cortical layers where the lateral extent of the metabolic and neuronal activation is larger compared to that in layer IV. In addition, we found that the measured spatial extent of the CMRO 2 changes was insensitive to assumptions made in the calculation of the CMRO 2 changes such as baseline hemoglobin concentrations, vascular weighting constants, and wavelength dependence of tissue scattering. Multi-parameter full field imaging of the functional response provides a more complete picture of the hemodynamic response to functional activation including the spatial and temporal estimation of CMRO 2 changes. D
Cerebral oxygen demand for short-lived and steady-state events
Journal of Neurochemistry, 2009
Due to importance of oxidative energetics for cerebral function, extraction of oxygen consumption (CMR O2) from blood oxygenation level dependent (BOLD) signal using multi-modal measurements of blood flow (CBF) and volume (CBV) has become an accepted functional magnetic resonance imaging (fMRI) technique. This approach, termed calibrated fMRI, is based on a biophysical model which describes tissue oxygen extraction at steady-state. A problem encountered for calculating dynamic CMR O2 relates to concerns whether the conventional BOLD model can be applied transiently. In particular, it is unclear whether calculation of CMR O2 differs between short and long stimuli. Linearity was experimentally demonstrated between BOLDrelated components and neural activity, thereby making it possible to use calibrated fMRI in a dynamic manner. We used multi-modal fMRI and electrophysiology, in α-chloralose anesthetized rats during forepaw stimulation to show that respective transfer functions (of BOLD, CBV, CBF) generated by deconvolution with neural activity are time invariant, for events in the millisecond to minute range. These results allowed extraction of a significant component of the BOLD signal that can be ascribed to CMR O2 transients. We discuss the importance of minimizing residual signal, represented by the difference between modeled and raw signals, in convolution analysis using multi-modal signals.
Journal of Cerebral Blood Flow & Metabolism, 1999
To test the hypothesis that brain oxidative metabo lism is significantly increased upon adequate stimulation, we varied the presentation of a visual stimulus to determine the frequency at which the metabolic response would be at maxi mum, The authors measured regional CMRo in 12 healthy normal volunteers with the ECAT EXACT HR� (CTIISiemens, Knoxville, TN, U,S,A,) three-dimensional whole-body positron emission tomograph (PET). In seven successive activating con ditions, subjects viewed a yellow-blue annular checkerboard reversing its contrast at frequencies of 0, 1,4,8, 16,32, and 50
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.
Trial-by-trial relationship between neural activity, oxygen consumption, and blood flow responses
NeuroImage, 2008
Trial-by-trial variability in local field potential (LFP), tissue partial pressure of oxygen (PO2), cerebral blood flow (CBF), and deoxyhemoglobin-weighted optical imaging of intrinsic signals (OIS) were tested in the rat somatosensory cortex while fixed electrical forepaw stimulation (1.0-ms pulses with amplitude of 1.2 mA at a frequency of 6 Hz) was repeatedly applied. The changes in the cerebral metabolic rate of oxygen (CMRO2) were also evaluated using a hypotension condition established by our group based on the administration of a vasodilator. Under normal conditions, CBF, PO2, and OIS showed positive signal changes (48%, 32%, and 0.42%, respectively) following stimulation. Over multiple trials, the CBF responses were well correlated with the integral of the LFP amplitudes (sigmaLFP) (Rmean=0.78), whereas a lower correlation was found between PO2 and sigmaLFP (Rmean=0.60) and between OIS and sigmaLFP (Rmean=0.54). Under the hypotension condition the LFP responses were preserved, but the CBF responses were suppressed and the PO2 and OIS changes were negative (-12% and -0.28%, respectively). In this condition, the trial-by-trial variations in PO2 and OIS were well correlated with the variability in sigmaLFPs (Rmean= -0.77 and -0.76, respectively), indicating a single trial coupling between CMRO2 changes and sigmaLFP. These findings show that CBF and CMRO2 signals are more directly correlated with neural activity compared to blood oxygen-sensitive methods such as OIS and BOLD fMRI.