The potential for gas-free measurements of absolute oxygen metabolism during both baseline and activation states in the human brain

Liu, Eulanca Y.; Guo, Jia; Simon, Aaron B.; Haist, Frank; Dubowitz, David J.; Buxton, Richard B.

doi:10.1101/705186

Cited by 3 publications

(9 citation statements)

References 53 publications

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“…Data processing was done as described by Liu et al 16 . Field map correction was first performed on raw ASL data to account for magnetic field inhomogeneities 33 .…”

Section: Image Preprocessingmentioning

confidence: 99%

“…Surround-averaging was applied to the first-and second-echo images; these values were used to calculate BOLD R2*-weighted images. For each time series, after ROI selection (described below), the mean R2* was subtracted to form ∆R2*(t) time series, which were then converted back to dBOLD signal without systematic effects of drift 16 .…”

Section: Image Preprocessingmentioning

confidence: 99%

“…In each of the two baseline states, a measurement of venous oxygenation was made using Velocity-Selective Excitation and Arterial Nulling (VSEAN) 22 developed by Guo and Wong and tested in a previous study 16 . The VSEAN pulse sequence is applied on one slice at a time, and works by combining arterial nulling and a velocity selective module to isolate the signal of venous blood, and then measuring the signal decay rate R2 with a spin-echo module using three effective echo times of 25, 50 and 75 ms. Other pulse sequence parameters were: FOV = 256 mm x 256 mm, single-slice spin echo with spatial-spectral excitation, two slice-selective hyperbolic secant refocusing pulses, single-shot spiral readout, ve=2 cm/s in sliceselective direction, slice-selective post-saturation pulses, 81 acquisitions preceded by two dummy scans and including six "cos" modulated reference scans 22 .…”

Section: Vsean Acquisitionmentioning

confidence: 99%

“…The OEF was then taken as 1-Yv, based on the assumptions that arterial hemoglobin was fully saturated with oxygen and dissolved O2 is negligible compared to hemoglobin-bound O2. Detailed acquisition and analysis parameters were as reported in a previous manuscript 16 .…”

Section: Calculation Of Baseline Oefmentioning

confidence: 99%

“…In the current study we complemented the ASL/BOLD experiment with two different MRI methods that do not require the subject to breathe special gases, but are sensitive to the additional needed physiological parameters of the baseline state 16 . As with the BOLD effect, the physical basis of these tools is the effect of deoxyhemoglobin on the relaxation rate of the precessing transverse magnetization that generates the MR signal.…”

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confidence: 99%

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Resolving intrinsic ambiguities of the fMRI signal in the human brain

Liu¹,

Haist²,

Shin

et al. 2019

Preprint

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Resolving intrinsic ambiguities of the fMRI signal in the human brain Functional magnetic resonance imaging (fMRI) using the blood oxygenation level dependent (BOLD) signal is a standard tool in human neuroscience studies. However, the BOLD signal is physiologically complex, depending on the baseline state of the brain and the balance of changes in blood flow and oxygen metabolism in response to a change in neural activity. Interpretation of the magnitude of the BOLD response is thus problematic; specifically, group differences of the BOLD response to a standard task or stimulus, or a change after administration of a drug, could be due to a change in the neural response, neurovascular coupling, or the baseline state. While changes in oxygen metabolism can serve as a biomarker of neural activity change, reflecting the energy cost of activity, oxygen metabolism cannot be estimated from BOLD measurements alone. Here we used the effects of caffeine as a test case to show that a suite of additional noninvasive measurements, requiring no manipulation of inhaled gases, makes it possible to untangle the underlying effects of caffeine on blood flow and oxygen metabolism. After caffeine administration, the BOLD response to a standard motor task was reduced, but oxygen metabolism was not reduced; rather, caffeine reduced the balance of blood flow relative to oxygen metabolism, both in the baseline state and in response to the task. The MRI methods used required only an additional 12 minutes of scanning, can be implemented on any MRI system, and painted a more complete picture of the physiological effects of caffeine. In addition to the assessment of drug effects in the human brain, these methods make it possible to resolve ambiguities of the BOLD signal in studies of development, aging, and disease.The cerebral metabolic rate of oxygen (CMRO2) reflects energy generation from oxidative metabolism of glucose. It is dominantly driven by processes related to neural signaling, primarily the cost of restoring sodium and calcium gradients across cellular membranes following excitatory synaptic activity 2 . Oxygen is delivered to the tissue by cerebral blood flow (CBF) with the balance of CMRO2 and CBF rates reflected by the oxygen extraction fraction (OEF), or the fraction of arterial blood oxygen extracted in passing through the capillary bed and metabolized in the tissue mitochondria.Empirically, the OEF is relatively uniform in the resting human brain with a value of about 0.4 3 . The essential yet unexpected physiological phenomenon is that when neural activity increases in response to a task or stimulus, the fractional CBF change is much 3 larger than the fractional CMRO2 change, by a factor of two or more, with the seemingly paradoxical effect of reducing the OEF when CMRO2 increases 4 . The biological function served by the large CBF increase may be to prevent a fall in the tissue oxygen concentration, although current evidence indicates that dynamic CBF modulation is controlled in a feedforward manner by mechanisms related...

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“…Data processing was done as described by Liu et al 16 . Field map correction was first performed on raw ASL data to account for magnetic field inhomogeneities 33 .…”

Section: Image Preprocessingmentioning

confidence: 99%

Section: Image Preprocessingmentioning

confidence: 99%

Section: Vsean Acquisitionmentioning

confidence: 99%

Section: Calculation Of Baseline Oefmentioning

confidence: 99%

mentioning

confidence: 99%

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Resolving intrinsic ambiguities of the fMRI signal in the human brain

Liu¹,

Haist²,

Shin

et al. 2019

Preprint

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Three‐dimensional whole‐brain mapping of cerebral blood volume and venous cerebral blood volume using Fourier transform–based velocity‐selective pulse trains

Liu

Zijl

et al. 2021

Magnetic Resonance in Med

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Purpose To develop 3D MRI methods for cerebral blood volume (CBV) and venous cerebral blood volume (vCBV) estimation with whole‐brain coverage using Fourier transform–based velocity‐selective (FT‐VS) pulse trains. Methods For CBV measurement, FT‐VS saturation pulse trains were used to suppress static tissue, whereas CSF contamination was corrected voxel‐by‐voxel using a multi‐readout acquisition and a fast CSF T2 scan. The vCBV mapping was achieved by inserting an arterial‐nulling module that included a FT‐VS inversion pulse train. Using these methods, CBV and vCBV maps were obtained on 6 healthy volunteers at 3 T. Results The mean CBV and vCBV values in gray matter and white matter in different areas of the brain showed high correlation (r = 0.95 and P < .0001). The averaged CBV and vCBV values of the whole brain were 5.4 ± 0.6 mL/100 g and 2.5 ± 0.3 mL/100 g in gray matter, and 2.6 ± 0.5 mL/100 g and 1.5 ± 0.2 mL/100 g in white matter, respectively, comparable to the literature. Conclusion The feasibility of FT‐VS‐based CBV and vCBV estimation was demonstrated for 3D acquisition with large spatial coverage.

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The thermodynamics of thinking: connections between neural activity, energy metabolism and blood flow

Buxton

2019

Preprint

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Supplementary Information is contained in a separate file 2 Summary Functional magnetic resonance imaging (fMRI) and other current functional neuroimaging methods are sensitive to cerebral metabolism and cerebral blood flow (CBF) rather than the underlying neural activity itself. Current studies have shown that the connections between metabolism, flow and neural activity are complex and somewhat counterintuitive: CBF and glycolysis increase more than seems to be needed to provide oxygen and pyruvate for oxidative metabolism in the mitochondria; the oxygen extraction fraction is relatively low in the brain and decreases when oxygen metabolism increases;and it appears that inhibitory neural activity is an important driver of CBF, even though such activity is likely to have less of an energy cost in terms of ATP consumption compared with excitatory activity. This work lays a foundation for the idea that this unexpected pattern of physiological changes is consistent with basic thermodynamic considerations related to metabolism. In the context of this thermodynamic framework, the apparent mismatches in metabolic rates and CBF are related to preserving the entropy change of oxidative metabolism, specifically the O 2 /CO 2 ratio in the mitochondria.However, the mechanism supporting this CBF response is likely not due to feedback from a hypothetical O 2 sensor in tissue, but rather is consistent with feed-forward control by signals from both excitatory and inhibitory neural activity. Quantitative predictions of the thermodynamic framework, based on models of O 2 and CO 2 transport and possible neural drivers of CBF control, are in good agreement with a wide range of experimental data, including responses to neural activation, hypercapnia, hypoxia and high altitude acclimatization.3

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The potential for gas-free measurements of absolute oxygen metabolism during both baseline and activation states in the human brain

Cited by 3 publications

References 53 publications

Resolving intrinsic ambiguities of the fMRI signal in the human brain

Resolving intrinsic ambiguities of the fMRI signal in the human brain

Three‐dimensional whole‐brain mapping of cerebral blood volume and venous cerebral blood volume using Fourier transform–based velocity‐selective pulse trains

The thermodynamics of thinking: connections between neural activity, energy metabolism and blood flow

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