Anesthetic effects on regional CBF, BOLD, and the coupling between task-induced changes in CBF and BOLD: an fMRI study in normal human subjects

Abstract

Functional MR imaging was performed in sixteen healthy human subjects measuring both regional cerebral blood flow (CBF) and blood oxygen level dependent (BOLD) signal when visual and auditory stimuli were presented to subjects in the presence or absence of anesthesia. During anesthesia, 0.25 mean alveolar concentration (MAC) sevoflurane was administrated. We found that low-dose sevoflurane decreased the task-induced changes in both BOLD and CBF. Within the visual and auditory regions of interest inspected, both baseline CBF and the task-induced changes in CBF decreased significantly during anesthesia. Low-dose sevoflurane significantly altered the task-induced CBF-BOLD coupling; for a unit change of CBF, a larger change in BOLD was observed in the anesthesia condition than in the anesthesia-free condition. Low-dose sevoflurane was also found to have significant impact on the spatial nonuniformity of the task-induced coupling. The alteration of task-induced CBF-BOLD coupling by low-dose sevoflurane introduces ambiguity to the direct interpretation of functional MRI (fMRI) data based on only one of the indirect measures-CBF or BOLD. Our observations also indicate that the manipulation of the brain with an anesthetic agent complicates the model-based quantitative interpretation of fMRI data, in which the relative task-induced changes in oxidative metabolism are calculated by means of a calibrated model given the relative changes in the indirect vascular measures, usually CBF and BOLD.

(c) 2008 Wiley-Liss, Inc.

Figures

FIG. 1

Changes in BOLD (a) and regional CBF (b) induced by the visual and auditory stimulations. The t-statistic was estimated on the pooled-subject data and is shown as a color bar on the right. a: BOLD activations are given for the sevoflurane-free (top) and anesthesia (bottom) conditions, respectively. b: Task-induced changes in CBF are demonstrated for the anesthesia-free condition (top), compared with those during anesthesia (bottom). c: Typical slices of the absolute regional CBF measured with ASL for the resting condition when no sevoflurane was given to the subjects (pooled-subject data); the gray scale is in mL/100 g/min.

FIG. 2

a,b: Resting-state baseline CBF and task-induced changes in CBF were estimated within the visual (a) and auditory (b) ROIs for the anesthesia-free and anesthesia conditions. Paired t-test per subjects was performed to evaluate the anesthetic effect on both resting state CBF and the task-induced changes. Asterisks show the significance (*P < 0.05; **P < 0.01) from the paired t-test for the resting state CBF values (white) and the task-induced changes (gray).

FIG. 3

Regional CBF-BOLD coupling was assessed in the visual ROI in the anesthesia-free (blue O) and anesthesia (green X) conditions. A composite map representing visual task-induced changes in BOLD in the anesthesia-free condition was estimated on a per voxel basis on the pooled-subject data in the transformed common brain template space. The ROI was defined based on the composite map of task-induced BOLD changes and Bonferroni correction was applied for multiple voxel comparisons (P < 0.01). Within the visual ROI, each voxel is associated with the changes in both CBF and BOLD induced by the visual stimulus (inset), that is ΔCBF and ΔBOLD. Scatter plots are presented for the anesthesia-free and anesthesia conditions. a: The data are displayed as a collection of points, each representing the coordinated ΔCBF and ΔBOLD induced by the visual stimulus for one voxel within the ROI (abscissa ΔBOLD and ordinate ΔCBF). The prediction lines with 95% confidence bounds, the regression equations with estimates and their standard errors, and R-values for the goodness of fit are presented. b: Also estimated were relative changes in CBF and BOLD, calculated as ΔCBF/CBF and ΔBOLD/BOLD, where the denominator represents the baseline signal in the absence of stimuli.

FIG. 4

Regional CBF-BOLD coupling was assessed in the auditory ROI in the anesthesia-free (blue O) and anesthesia (green X) conditions. A composite map representing auditory task-induced changes in BOLD in the anesthesia-free condition was estimated on a per voxel basis on the pooled-subject data in the transformed common brain template space. The ROI was defined based on the composite map of task-induced BOLD changes and Bonferroni correction was applied for multiple voxel comparisons (P < 0.01). Within the auditory ROI, each voxel is associated with the changes in both CBF and BOLD induced by the auditory stimulus (see the Materials and Methods section), that is, ΔCBF and ΔBOLD. Scatter plots are presented for the anesthesia-free and anesthesia conditions. a: The data are displayed as a collection of points, each representing the coordinated ΔCBF and ΔBOLD induced by the auditory stimulus for one voxel within the ROI (abscissa ΔBOLD and ordinate ΔCBF). The prediction lines with 95% confidence bounds, the regression equations with estimates and their standard errors, and R-values for the goodness of fit are presented. b: Also estimated were relative changes in CBF and BOLD, calculated as ΔCBF/CBF and ΔBOLD/BOLD, where the denominator represents the baseline signal in the absence of stimuli.

FIG. 5

Data were simulated using an fMRI quantitative model (39) with the following default parameters: α = 0.38, β = 1.5, and M = 0.08. Mean task-induced relative changes in BOLD and CBF was plotted for two ROIs (visual marked by circles and auditory by squares) and for two conditions (awake by blue empty symbols and anesthesia by green solid). Iso-CMRO2 curves (black) were calculated based on the default model parameters. When there is a change assumed in parameter α, β, or M, simulated iso-CMRO2 curves are shown in red. The sign of the change in α, β, or M was chosen to decrease the slope of the regression line of BOLD-CBF coupling, as observed in this study. Because saturation of the BOLD signal causes nonlinearity of BOLD-CBF coupling and an increase in CMRO2 trends to reduce the saturation and thus the nonlinearity, the iso-CMRO2 lines give the upper limit of the nonlinearity. The parallel iso-CMRO2 curves/lines validate our assumption that the task-induced changes in CBF and BOLD were within the linear regime of the BOLD-CBF coupling relationship.