New insights into central roles of cerebral oxygen metabolism in the resting and stimulus-evoked brain

Abstract

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.

Figure 1

Significant CMRO₂ increase in activated visual cortex. Three-dimensional CMRO₂ maps obtained at resting (second column from the left) and stimulated (third column) conditions; 3D functional metabolic activation maps showing percent changes of CMRO₂ elevated by visual stimulation (fourth column); BOLD-based fMRI maps (fifth column); and anatomic brain images (first column) in four adjacent image slices from a representative cat brain.

Figure 2

Summary of resting and activated CMRO₂ and percent changes. Summarized absolute CMRO₂ values measured at resting and during visual stimulation (top inserts) and their percent changes (bottom inserts) from four CMRO₂ image slices covering the visual cortex of cat anesthetized with isoflurane. (A) Results from a representative cat. (B) Averaged results from six experiments, for the ¹⁷O MRSI voxels with only positive CMRO₂ change. (C) Averaged results from six experiments for the ¹⁷O MRSI voxels with both positive and negative CMRO₂ changes. Paired t-test indicates a statistically significant difference between the control and activated CMRO₂ values (P < 0.005 using paired t-test for both panels B and C).

Figure 3

Stimulus-evoked CMRO₂ increase and its relation to resting CMRO₂. (A) Averaged absolute CMRO₂ values for each cat brain at resting and during visual stimulation. (B) The averaged percent CMRO₂ increases elevated by visual stimulation. (C) The negative correlation between the percent CMRO₂ changes and baseline CMRO₂ values. This figure shows that visual stimulation elevates a significant CMRO₂ increase in the activated visual cortex of five cats studied (P < 0.005 using paired t-test for both panels A and B), and the percent CMRO₂ changes are negatively correlated to the corresponding baseline CMRO₂ levels.

Figure 4

Spatially compensated CMRO₂ changes elevated by brain stimulation. Functional CMRO₂ maps (show both positive and negative changes) and fMRI BOLD maps during visual stimulation from two representative cats. This figure shows that the CMRO₂ increases in the central activated visual cortex regions are commonly accompanied by CMRO₂ decreases in surrounding brain regions.