The Effect of Labeling Parameters on Perfusion-Based fMRI in Nonhuman Primates

Abstract

The blood oxygenation level-dependent (BOLD) signal is the most commonly used modality of functional magnetic resonance imaging (fMRI) today. Although easy to implement, it is an ambiguous signal since it results from a combination of several hemodynamic factors. Functional cerebral blood flow changes, as measured by using arterial spin labeling (ASL), typically occur in the parenchyma and have been demonstrated to be more closely coupled to neural activation compared with BOLD. However, the intrinsically low signals from ASL techniques have hindered its widespread application to fMRI for basic research and even more so for clinical applications. Here, we report the first implementation of continuous ASL in the anaesthetized macaque at high magnetic field of 7 T. The technique was optimized to permit maximum signal-to-noise ratio of functional perfusion-based images at high spatial resolution. The effect of labeling parameters, such as label time and post-label delay (PLD), on functional cerebral blood flow (fCBF) in the visual cortex was evaluated. Functional cerebral blood flow maps did not change with increasing label time after 2,000 ms, indicating that a label time of 2,000 ms is sufficient for reliable mapping of fCBF. The percent changes obtained using fCBF were better localized to gray matter, than those obtained with BOLD. A short PLD of 200 ms revealed significantly higher fCBF changes at the cortical surface, indicating large-vessel contamination, than a long PLD of 800 ms. However, the effect of the PLD on fCBF was smaller than on baseline CBF. These results are of importance for high-resolution applications, and when accurate quantification is required for studies in monkeys as well as in humans.

Dopamine-Induced Dissociation of BOLD and Neural Activity in Macaque Visual Cortex

“…Figure 4A shows fCBF in early visual cortex, and Figure 4B shows the averaged time course of the CBF across experiments. There was a reliable, visually induced CBF modulation of 19% 6 7% during the predrug period, in agreement with earlier studies [11]. During the ''drug'' period, we observed an increase in modulation by 34% (MOD drug = 134% 6 10%; p = 0.045).…”

“…Figure 1C shows the changes in the BOLD response over the course of the LDC injection. BOLD modulation in the predrug period was 2.5% 6 1.1%, which is typical for anesthetized monkeys at 7T [9][10][11]. During the drug infusion, we observed a significant reduction in the visually induced modulation (Figures 1C and 1D; MOD drug = 50% 6 5.3%; p = 0.034), which was sustained after the infusion was stopped (MOD post = 60% 6 4.2%; p = 0.05).…”

Analysis of Cerebral Hemodynamics in Healthy Adult Rhesus with Dynamic Susceptibility Contrast Perfusion (DSC-MR) Imaging

“…The findings were consistent with the previous human brain studies [9][10][11]. It is similar to the activity of normal human brain that rCBF in cortex is significantly higher than that in white matter.…”

“…Mild hypothermia has been widely used nowadays and deep hypothermia is still being studied. As primate animals are close to humans, rhesus has been studied gradually since 2003 [5][6][7][8][9][10][11]. Theoretically, low brain temperature could improve the brain tolerance to hypoxia.…”

Effects of lactate on the early visual cortex of non-human primates, investigated by pharmaco-MRI and neurochemical analysis

“…4 depicts the mean of five CBF measurements after lactate infusion. We observed reliable visually-induced modulation in the CBF recordings in the range of 19 ± 7% (Zappe et al, 2008), but did not detect any significant baseline shifts comparable to the changes in the BOLD recordings.…”