Heterogeneous Oxygen Extraction in the Visual Cortex during Activation in Mild Hypoxic Hypoxia Revealed by Quantitative Functional Magnetic Resonance Imaging

Tuunanen, Pasi; Murray, Ian J.; Parry, Neil R. A.; Kauppinen, Risto A.

doi:10.1038/sj.jcbfm.9600186

Cited by 23 publications

(37 citation statements)

References 44 publications

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“…The detection of lactate is challenging due to its low concentration and limited chemical shift resolution of the 1 H spectrum. The increase in lactate sensitivity gained from higher field strength (3T), edited MRS and the lactate-specific analysis as applied here and previously (6) represents a development from other studies (13) that have not detected changes in lactate during a hypoxic challenge.…”

Section: Discussionmentioning

confidence: 76%

Temporal dynamics of lactate concentration in the human brain during acute inspiratory hypoxia

Harris

Roberton

Huckle

et al. 2012

Magnetic Resonance Imaging

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Purpose To demonstrate the feasibility of measuring the temporal dynamics of cerebral lactate concentration and examine these dynamics in human subjects using MRS during hypoxia. Methods A respiratory protocol consisting of 10 min baseline normoxia, 20 min inspiratory hypoxia and ending with 10 min normoxic recovery was used, throughout which lactate-edited MRS was performed. This was repeated four times in three subjects. A separate session was performed to measure blood lactate. Impulse response functions using end-tidal oxygen and blood lactate as system inputs and cerebral lactate as the system output were examined to describe the dynamics of the cerebral lactate response to a hypoxic challenge. Results The average lactate increase was 20%±15% during the last half of the hypoxic challenge. Significant changes in cerebral lactate concentration were observed after 400s. The average relative increase in blood lactate was 188%±95%. The temporal dynamics of cerebral lactate concentration was reproducibly demonstrated with 200s time bins of MRS data (coefficient of variation 0.063±0.035 between time bins in normoxia). The across subject coefficient of variation was 0.333. Conclusions The methods for measuring the dynamics of the cerebral lactate response developed here would be useful to further investigate the brain’s response to hypoxia.

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Section: Discussionmentioning

confidence: 76%

Temporal dynamics of lactate concentration in the human brain during acute inspiratory hypoxia

Harris

Roberton

Huckle

et al. 2012

Magnetic Resonance Imaging

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“…In addition, an increase in brain activity also leads to increased neurotransmitter cycling rates (24,29), which may ultimately change the concentrations of neurotransmitters such as glutamate/glutamine and γ-aminobutyric acid (28,30,31). For instance, the transient increases in the concentrations of lactate and glutamate, accompanied with the tendency of concentration decrease in Glc, have been observed in the human visual cortex during sustained visual stimulation (19,27,28,32,33). It was also reported that there are significant changes in a number of brain metabolites and neurotransmitters, including the ratio of PCr versus Cr, γ-aminobutyric acid, glutamine, and glutamate, as well as neurotransmission cycling rate at near-freezing body temperature in hibernating mammals (31).…”

Section: Discussionmentioning

confidence: 99%

In vivo proton MRS to quantify anesthetic effects of pentobarbital on cerebral metabolism and brain activity in rat

Zhang

Iltis

et al. 2009

Magnetic Resonance in Med

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To quantitatively investigate the effects of pentobarbital anesthesia on brain activity, brain metabolite concentrations and cerebral metabolic rate of glucose, in vivo proton MR spectra, and electroencephalography were measured in the rat brain with various doses of pentobarbital. The results show that (1) the resonances attributed to propylene glycol, a solvent in pentobarbital injection solution, can be robustly detected and quantified in the brain; (2) the concentration of most brain metabolites remained constant under the isoelectric state (silent electroencephalography) with a high dose of pentobarbital compared to mild isoflurane anesthesia condition, except for a reduction of 61% in the brain glucose level, which was associated with a 37% decrease in cerebral metabolic rate of glucose, suggesting a significant amount of "housekeeping" energy for maintaining brain cellular integrity under the isoelectric state; and (3) electroencephalography and cerebral metabolic activities were tightly coupled to the pentobarbital anesthesia depth and they can be indirectly quantified by the propylene glycol resonance signal at 1.13 ppm. This study indicates that in vivo proton MR spectroscopy can be used to measure changes in cerebral metabolite concentrations and cerebral metabolic rate of glucose under varied pentobarbital anesthesia states; moreover, the propylene glycol signal provides a sensitive biomarker for quantitatively monitoring these changes and anesthesia depth noninvasively. Key words: cerebral metabolic rate of glucose; CMR glc ; brain activity; brain metabolism; propylene glycol Sodium pentobarbital, one type of barbiturate, has been popularly used in clinic for treatment of seizures and preoperative sedation. It is also a common agent used for general anesthesia in clinical and animal research. Pentobarbital rapidly distributes to all tissues, with a higher concentration in brain, liver, and kidneys due to high lipid solubility. It can enhance the ␥-aminobutyric acid receptor-coupled response, thereby directly depressing neuronal excitability and resulting in an anesthesia effect in the brain and vanishing consciousness (see a recent review article, Alkire et al. (1), and references therein). The suppression of neuronal activity is also accompanied by significant depression of cerebral metabolic activity due to the inhibition of nicotinamide adenine dinucleotide (NADH) oxidation in the respiratory chain, and a deep pentobarbital anesthesia can induce a complete suppression of brain electroencephalography (EEG) activity thereby reaching an isoelectric state. Therefore, the delivery of pentobarbital into a living body can lead to a variety of brain physiologic changes, including EEG activity, cerebral metabolites/metabolic rates, and cerebral blood flow, and all these changes are expected to be related to the pentobarbital concentration reached inside the brain. It is thus essential to seek a robust, reliable tool to noninvasively assess the brain pentobarbital concentration in vivo and, ultimately, to ...

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“…Vafaee and Gjedde, 2000; Lu et al, 2004; Vafaee and Gjedde, 2004; Tuunanen and Kauppinen, 2006; Tuunanen et al, 2006; Chiarelli et al, 2007a,b; Ances et al, 2008; but, see Leenders et al, 1990). Mechanisms posited to mediate these differences include variation in oxygen metabolic requirements across cortex (Tuunanen et al, 2006), oxygen delivery, or blood flow alterations under certain conditions or in certain cortical areas (Vafaee and Gjedde, 2000; Lu et al, 2004), variable neurometabolic-flow coupling (Vafaee and Gjedde, 2004), and the accurate estimation of M (an index of maximal BOLD responding; Chiarelli et al, 2007a). Regardless of the precise mechanism behind this variability, the end result is that the BOLD response can be difficult to interpret across healthy, young cortex, and it can be even more complicated to interpret when making comparisons between younger and older groups (cf.…”

Section: Introductionmentioning

confidence: 99%

A BOLD Perspective on Age-Related Neurometabolic-Flow Coupling and Neural Efficiency Changes in Human Visual Cortex

Hutchison¹,

Shokri‐Kojori²,

Lu³

2013

Front. Psychol.

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Age-related performance declines in visual tasks have been attributed to reductions in processing efficiency. The neural basis of these declines has been explored by comparing the blood-oxygen-level-dependent (BOLD) index of neural activity in older and younger adults during visual task performance. However, neural activity is one of many factors that change with age and lead to BOLD signal differences. We investigated the origin of age-related BOLD changes by comparing blood flow and oxygen metabolic constituents of BOLD signal. Subjects periodically viewed flickering annuli and pressed a button when detecting luminance changes in a central fixation cross. Using magnetic resonance dualecho arterial spin labeling and CO 2 ingestion, we observed age-equivalent (i.e., similar in older and younger groups) fractional cerebral blood flow (∆CBF) in the presence of agerelated increases in fractional cerebral metabolic rate of oxygen (∆CMRO 2 ). Reductions in ∆CBF responsiveness to increased ∆CMRO 2 in elderly led to paradoxical age-related BOLD decreases. Age-related ∆CBF/∆CMRO 2 ratio decreases were associated with reaction times, suggesting that age-related slowing resulted from less efficient neural activity. We hypothesized that reduced vascular responsiveness to neural metabolic demand would lead to a reduction in ∆CBF/∆CMRO 2 . A simulation of BOLD relative to ∆CMRO 2 for lower and higher neurometabolic-flow coupling ratios (approximating those for old and young, respectively) indicated less BOLD signal change in old than young in relatively lower CMRO 2 ranges, as well as greater BOLD signal change in young compared to old in relatively higher CMRO 2 ranges. These results suggest that age-comparative studies relying on BOLD signal might be misinterpreted, as age-related BOLD changes do not merely reflect neural activity changes. Age-related declines in neurometabolic-flow coupling might lead to neural efficiency reductions that can adversely affect visual task performance.

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Heterogeneous Oxygen Extraction in the Visual Cortex during Activation in Mild Hypoxic Hypoxia Revealed by Quantitative Functional Magnetic Resonance Imaging

Cited by 23 publications

References 44 publications

Temporal dynamics of lactate concentration in the human brain during acute inspiratory hypoxia

Temporal dynamics of lactate concentration in the human brain during acute inspiratory hypoxia

In vivo proton MRS to quantify anesthetic effects of pentobarbital on cerebral metabolism and brain activity in rat

A BOLD Perspective on Age-Related Neurometabolic-Flow Coupling and Neural Efficiency Changes in Human Visual Cortex

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