Blood flow and oxygen delivery to human brain during functional activity: theoretical modeling and experimental data - PubMed (original) (raw)

Blood flow and oxygen delivery to human brain during functional activity: theoretical modeling and experimental data

M A Mintun et al. Proc Natl Acad Sci U S A. 2001.

Abstract

Coupling of cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO(2)) in physiologically activated brain states remains the subject of debates. Recently it was suggested that CBF is tightly coupled to oxidative metabolism in a nonlinear fashion. As part of this hypothesis, mathematical models of oxygen delivery to the brain have been described in which disproportionately large increases in CBF are necessary to sustain even small increases in CMRO(2) during activation. We have explored the coupling of CBF and oxygen delivery by using two complementary methods. First, a more complex mathematical model was tested that differs from those recently described in that no assumptions were made regarding tissue oxygen level. Second, [(15)O] water CBF positron emission tomography (PET) studies in nine healthy subjects were conducted during states of visual activation and hypoxia to examine the relationship of CBF and oxygen delivery. In contrast to previous reports, our model showed adequate tissue levels of oxygen could be maintained without the need for increased CBF or oxygen delivery. Similarly, the PET studies demonstrated that the regional increase in CBF during visual activation was not affected by hypoxia. These findings strongly indicate that the increase in CBF associated with physiological activation is regulated by factors other than local requirements in oxygen.

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Figures

Figure 1

Figure 1

Simulation results for pO2 distribution at baseline levels of CBF and CMRO2 (see Table 1). Oxygen tension decreases proceeding along the capillary and moving out radially from the capillary. In this model, the site of lowest oxygen tension, or “lethal corner,” is found in the brain tissue farthest from the capillary and at the level of the capillary exit. The figure shows that more than adequate oxygen levels exist for the entire brain volume.

Figure 2

Figure 2

Brain tissue oxygen levels in “lethal corner,” using model stimulation of hypoxia and neuronal activation. Hypoxia was superimposed in all three conditions, assuming an arterial pO2 of 45 mmHg. In all simulations, CBF was held fixed at baseline values to determine whether tissue pO2 would decrease below viable levels. The data show that, for all conditions, the brain maintains adequate levels of oxygen without need for raising CBF.

Figure 3

Figure 3

Blood flow images displayed as a midsagittal slice after averaging subject data in a standard atlas coordinate system. Image data were derived from quantitative PET blood flow scans that were normalized for variations in global blood flow. Each of nine subjects underwent scanning in two blocks: one block during breathing room air and a second block during hypoxia induced by reducing the inspired O2 fraction. In each block, PET studies were done during two control tasks and two visual activation tasks. (A) Average blood flow image from the control scans. (B) Mean subtraction image (visual activation minus control task) while breathing room air. (C) Average subtraction (visual activation minus visual fixation) image during hypoxia scaled to the same maximum as B. The black circle illustrates the relative size and position of the spherical region-of-interest used for quantitation of the regional visual cortex CBF. Note similarity in magnitude and distribution of the increased blood flow during visual activation. No augmentation of the blood flow response is seen despite the presence of reduced arterial oxygen content.

Figure 4

Figure 4

Effect of visual activation and hypoxia on visual cortex oxygen delivery. The regional oxygen delivery was calculated from the product of the subject's arterial oxygen content and PET-measured regional CBF. The data shown represent the mean and standard deviation of nine subjects (with each subject value representing the mean of two measurements in each of the four states). Oxygen delivery during activation + hypoxia was significantly less than oxygen delivery during activation alone (P < 0.05), demonstrating the lack of compensatory increase in CBF.

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