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

Abstract

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-spin-labeling 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.

Blood-flow magnetic resonance imaging of the retina

“…This is consistent with the notion that isoflurane is a known vasodilator (Matta et al, 1999) which has been well documented in the brain. In fact, cerebral blood flow under ~1% isoflurane (1.27±0.29 ml/g/min) is higher than awake restrained conditions (0.86±025 ml/g/min) in the same animals (Sicard et al, 2003a). Increasing isoflurane concentration from 1% to 2% increases cerebral blood flow from 0.87±0.27 to 1.31 ±0.30 ml/g/min in the same animals (Duong and Kim, 2000).…”

“…In the rat brain, hypercapnic (5% CO2 in air) inhalation increased cerebral blood flow by 25% (Sicard et al, 2003b) and 52% (Sicard and Duong, 2005) in rats under essentially identical experimental conditions (except the animals breathed spontaneously). The difference between spontaneous breathing in previous study of the rat brains and mechanical ventilation in this study could not explain the difference in response magnitude because animals under spontaneous breathing increase respiration rate which should slightly reduce blood CO 2 (Sicard and Duong, 2005).…”

Propofol allows precise quantitative arterial spin labelling functional magnetic resonance imaging in the rat

“…The use of anaesthesia in fMRI is not ideal as it suppresses basal cerebral blood flow (Sicard et al, 2003;Ueki et al, 1992), but without anaesthetics the images would be subject to movement artefact particularly in perfusion imaging. The user must be aware of the disadvantages when using anaesthetics; alpha chloralose decreases cerebral blood flow (Austin et al, 2005) and along with respiratory depression.…”

“…Under general anaesthesia blood pressure, respiration, and heart rate are depressed compared to the conscious state (Sicard et al, 2003). General anaesthetics also depress the metabolic activity of the central nervous system (CNS) and therefore reduce basal CBF (Ueki et al, 1992).…”

“…Studies using only Mivaurium, a neuromuscular blocker, have been carried out in rats (Peeters et al, 2001) but paralysis without concomitant anaesthesia is unethical and prohibited by law. Experiments have also been carried out on restrained conscious animals using BOLD imaging (Ferris et al, 2001;Lahti et al, 1998;Logothetis et al, 1999;Wyrwicz et al, 2000) and ASL imaging (Sicard et al, 2003), in an attempt to preserve neuronal coupling. Not only can motion artefact can cause a problem with this approach, but there is also associated neural activation from stress and motor cortical activation (Willis et al, 2001).…”