Regional Cerebral Blood Flow and BOLD Responses in Conscious and Anesthetized Rats under Basal and Hypercapnic Conditions: Implications for Functional MRI Studies

Abstract

Summary:Anesthetics, widely used in magnetic resonance imaging (MRI) studies to avoid movement artifacts, could have profound effects on cerebral blood flow (CBF) and cerebrovascular coupling relative to the awake condition. Quantitative CBF and tissue oxygenation (blood oxygen level-dependent [BOLD]) were measured, using the continuous arterial-spinlabeling technique with echo-planar-imaging acquisition, in awake and anesthetized (2% isoflurane) rats under basal and hypercapnic conditions. All basal blood gases were within physiologic ranges. Blood pressure, respiration, and heart rates were within physiologic ranges in the awake condition but were depressed under anesthesia (P < 0.05). Regional CBF was heterogeneous with whole-brain CBF values of 0.86 ± 0.25 and 1.27 ± 0.29 mL · g −1 · min −1 under awake and anesthetized conditions, respectively. Surprisingly, CBF was markedly higher (20% to 70% across different brain conditions) under isoflurane-anesthetized condition compared with the awake state (P < 0.01). Hypercapnia decreased pH, and increased PCO 2 and PO 2 . During 5% CO 2 challenge, under awake and anesthetized conditions, respectively, CBF increased 51 ± 11% and 25 ± 4%, and BOLD increased 7.3 ± 0.7% and 5.4 ± 0.4%. During 10% CO 2 challenge, CBF increased 158 ± 28% and 47 ± 11%, and BOLD increased 12.5 ± 0.9% and 7.2 ± 0.5%. Since CBF and BOLD responses were substantially higher under awake condition whereas blood gases were not statistically different, it was concluded that cerebrovascular reactivity was suppressed by anesthetics. This study also shows that perfusion and perfusion-based functional MRI can be performed in awake animals.

Haemodynamic and neural responses to hypercapnia in the awake rat

“…Trained animals rarely struggled and never vocalized, and grooming behaviour was occasionally observed. Sicard et al (2003) restrained animals using a restrainer similar to that described in Lahti et al (1998) with ear-, nose-, tooth-and shoulder-restraining bars in addition to a body-restraining tube. Additionally, they catheterized the femoral artery and vein.…”

Functionalized Lipopeptide Micelles as Highly Efficient NMR Depolarization Seed Points for Targeted Cell Labelling in Xenon MRI

“…Cerebral blood volume (CBV) can be measured using dynamic contrast‐enhanced MRI4 (with Gd‐based contrast agents, GBCAs). As such, MRI combines several advantages but lacks a sensitive direct access to microvascular tissue: Beside the ongoing discussion concerning the safety of GBCAs, both CBV and CBF measurements represent only an indirect access to microvasculature proliferation by detecting the contained blood and are prone to errors, particularly due to anesthesia impacts 6,7. A direct detection of brain microvascular endothelial cells would thus be the preferred strategy.…”

Diffusion tensor and perfusion MRI of non-human primates

“…The major cause of such difference is likely due to isoflurane anesthetic which is an established potent vasodilator. Similarly high CBF under isoflurane (67, 68) relative to other anesthetics (60) and awake conditions (68) have been well documented in rodents (isoflurane:awake CBF ratio in rat was 1.48 (60, 68) and the isoflurane:α-chloralose CBF ratio was 1.84 (68)). NHP CBF measurements have also been reported on a Bruker scanner using the built-in second RF channel (69, 70).…”