Effect of hypoxia and hyperoxia on cerebral blood flow, blood oxygenation, and oxidative metabolism

Abstract

Characterizing the effect of oxygen (O(2)) modulation on the brain may provide a better understanding of several clinically relevant problems, including acute mountain sickness and hyperoxic therapy in patients with traumatic brain injury or ischemia. Quantifying the O(2) effects on brain metabolism is also critical when using this physiologic maneuver to calibrate functional magnetic resonance imaging (fMRI) signals. Although intuitively crucial, the question of whether the brain's metabolic rate depends on the amount of O(2) available has not been addressed in detail previously. This can be largely attributed to the scarcity and complexity of measurement techniques. Recently, we have developed an MR method that provides a noninvasive (devoid of exogenous agents), rapid (<5 minutes), and reliable (coefficient of variant, CoV <3%) measurement of the global cerebral metabolic rate of O(2) (CMRO(2)). In the present study, we evaluated metabolic and vascular responses to manipulation of the fraction of inspired O(2) (FiO(2)). Hypoxia with 14% FiO(2) was found to increase both CMRO(2) (5.0±2.0%, N=16, P=0.02) and cerebral blood flow (CBF) (9.8±2.3%, P<0.001). However, hyperoxia decreased CMRO(2) by 10.3±1.5% (P<0.001) and 16.9±2.7% (P<0.001) for FiO(2) of 50% and 98%, respectively. The CBF showed minimal changes with hyperoxia. Our results suggest that modulation of inspired O(2) alters brain metabolism in a dose-dependent manner.

Figures

Figure 1

Illustration of experimental paradigm and time courses of arterial oxygen content, [O2]a, and cerebral blood flow (CBF). During the session, the subject breathed 21%, 14%, 50%, and 98% fraction of inspired O2 (FiO2) for 8, 18, 15, and 12 minutes, respectively, and these are denoted by different colors in the plot. The duration of each condition was preset based on the time needed to reach a new steady state that was determined from several testing experiments. Magnetic resonance imaging (MRI) data acquisitions were performed throughout the session and the type of pulse sequence performed is denoted as dots or bars at the top of the plot, where each dot indicates a 0.5-minute phase-contrast MRI and each bar indicates a 3.2-minute T2-Relaxation-Under-Spin-Tagging (TRUST) MRI. Due to the large number and high density of the phase-contrast scans, the data allowed the assessment of time course of CBF changes (blue curve) during the experiment (the gap in the curve is due to the TRUST scan). For comparison, [O2]a (accounting for both hemoglobin-bound and dissolved O2) time course is also display (red curve). The color reproduction of this figure is available at the Journal of Cerebral Blood Flow and Metabolism journal online.

Figure 2

Representative magnetic resonance imaging (MRI) data obtained in the experiment. (A) Typical T2-Relaxation-Under-Spin-Tagging (TRUST) MRI data under different fraction of inspired O2 (FiO2) conditions. Under each condition, control and tagged types of images were acquired, the subtraction of which yielded pure blood signal. In this study, the venous signal in the primary draining vein, sagittal sinus (center of the yellow box), was used for quantitative analysis. (B) In the TRUST sequence, the signal was acquired at different effective echo time (TE) values. Thus, the fitting of the signal as a function of effective TE can provide an estimation of blood T2. The legend shows that T2 increases with FiO2 value. (C) Using a calibration plot established previously, the blood T2 can be converted to blood oxygenation, given the subject's hematocrit value. (D) Representative phase-contrast MR images under different FiO2 conditions. In these images, head-to-foot flow direction is displayed as black color. Thus, the darker the voxel appears, the higher the flow velocity is. The color reproduction of this figure is available at the Journal of Cerebral Blood Flow and Metabolism journal online.

Figure 3

Percent changes in cerebral metabolic rate of oxygen (CMRO2) and cerebral blood flow (CBF) due to fraction of inspired O2 (FiO2) modulation. The changes were calculated based on comparisons between the special gas mixture and room air.

Figure 4

Scatter plots comparing (A) ΔCMRO2/CMRO2 with Δ[O2]a and (B) ΔCBF/CBF to Δ[O2]a. Even given the same fraction of inspired O2 (FiO2) gas type, different individuals manifest slightly different Δ[O2]a values. Thus, the use of Δ[O2]a allows a more accurate assessment of the dependence of brain physiology on O2 content. CBF, cerebral blood flow; CMRO2, cerebral metabolic rate of oxygen.