Baseline CBF, and BOLD, CBF, and CMRO2 fMRI of visual and vibrotactile stimulations in baboons

Abstract

Neurovascular coupling associated with visual and vibrotactile stimulations in baboons anesthetized sequentially with isoflurane and ketamine was evaluated using multimodal functional magnetic resonance imaging (fMRI) on a clinical 3-Tesla scanner. Basal cerebral blood flow (CBF), and combined blood-oxygenation-level-dependent (BOLD) and CBF fMRI of visual and somatosensory stimulations were measured using pseudo-continuous arterial spin labeling. Changes in stimulus-evoked cerebral metabolic rate of oxygen (CMRO(2)) were estimated using calibrated fMRI. Arterial transit time for vessel, gray matter (GM), and white matter (WM) were 250, 570, and 823 ms, respectively. Gray matter and WM CBF, respectively, were 107.8±7.9 and 47.8±3.8 mL per 100 g per minute under isoflurane, and 108.8±10.3 and 48.7±4.2 mL per 100 g per minute under ketamine (mean±s.e.m., N=8 sessions, five baboons). The GM/WM CBF ratio was not statistically different between the two anesthetics, averaging 2.3±0.1. Hypercapnia evoked global BOLD and CBF increases. Blood-oxygenation-level-dependent, CBF, and CMRO(2) signal changes by visual and vibrotactile stimulations were 0.19% to 0.22%, 18% to 23%, and 4.9% to 6.7%, respectively. The CBF/CMRO(2) ratio was 2.9 to 4.7. Basal CBF and fMRI responses were not statistically different between the two anesthetics. This study establishes a multimodal fMRI protocol to probe clinically relevant functional, physiological and metabolic information in large nonhuman primates.

Figure 1

Group-averaged perfusion-weighted arterial spin labeling signal (ΔM/M₀) at different post-labeling delays in baboons (mean±s.e.m., N=6). Analysis was performed for white matter (WM), gray matter (GM), and vessel regions of interest. The lines are model fits (equation (1)) to the experimental data. The turning points (arrows) indicate arterial transit times (ATTs). The ATT of vessels, GM, and WM were 250, 570, and 823 ms, respectively.

Figure 2

Baseline quantitative cerebral blood flow images at 2 × 2 × 5 mm resolution under (A) isoflurane and (B) ketamine from a representative baboon (scale bar=0 to 150 mL per 100 g per minute). The images were acquired in 3.5 minutes with the optimal post-labeling delay of 700 ms.

Figure 3

Quantitative cerebral blood flow (CBF) under basal condition and hypercapnia for gray matter (GM) and white matter (WM) in baboons under (A) isoflurane and (B) ketamine (mean±s.e.m., N=6 trials in six sessions for each anesthetics from five animals). Hypercapnia-induced CBF magnitude changes are shown in gray color. Hypercapnia-induced percent changes are displayed in numerical values. (^*,#P<0.05).

Figure 4

(A) Blood-oxygenation-level-dependent (BOLD) and (B) cerebral blood flow (CBF) activation maps in response to simultaneous binocular visual and unilateral vibrotactile stimulations to the right hand from a representative ketamine-anesthetized baboon. The color scale indicates statistical Z-scores from 2.3 to 6. (C, E) BOLD and (D, F) CBF functional magnetic resonance imaging responses time courses were shown for both isoflurane and ketamine (mean±s.e.m., N=9 trials; blue solid line: visual cortex, red dash line: somatosensory cortex).

Figure 5

Scatter plots of (top) blood-oxygenation-level-dependent (BOLD) versus cerebral blood flow (CBF) changes and (bottom) cerebral metabolic rate of oxygen (CMRO₂) versus CBF changes by simultaneous visual and vibrotactile stimulations from individual trials (N=9 for primary visual cortex and N=9 for the primary somatosensory cortex).