Measurement of Regional Substrate Utilization Rates by Emission Tomography

Raichle, M. E.; Welch, M. J.; Rl, Grubb; Higgins, C. S.; Ter‐Pogossian, Michel M.; Kb, Larson

doi:10.1126/science.414358

Cited by 72 publications

(12 citation statements)

References 6 publications

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“…Cats of either sex weighing between 3.5 and 4.0 kg were anesthetized with pentobarbital (40 mg/kg of body weight), immobilized with gallamine, and ventilated mechanically with 30% O a and 70% N 3 . Arterial blood gases were measured at predetermined intervals and arterial pressure was monitored continuously via femoral catheters.…”

Section: Methodsmentioning

confidence: 99%

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Correlation between glucose utilization and metabolite levels during focal ischemia in cat brain.

Welsh

Greenberg

Jones

et al. 1980

Stroke

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MEASUREMENT of the cerebral rate of glucose consumption using radioactively labeled glucose 1 or glucose analogs 2 has potentially valuable clinical application.3 ' * These methods, however, do not distinguish between aerobic and anaerobic utilization of glucose. This distinction is particularly important for damaged brain in which the fraction of glucose metabolized anaerobically may be greater than normal. The presence of anaerobiosis can be detected by other methods, such as measurement of tissue levels of lactate. Thus, by combining a measure of tissue metabolite levels with a measure of glucose utilization, it is possible to make a qualitative distinction between aerobic and anaerobic metabolism.Marked regional variations in the rate of glucose consumption have been demonstrated in experimental models of cerebral ischemia 6 '" and hypoxia 7 using the f'4 C] deoxyglucose autoradiographic technique.1 Thus, occluding the middle cerebral artery in the cat resulted in closely juxtaposed regions of increased and decreased glucose utilization within the ischemic hemisphere. 6 Using the same model for the present study we have measured tissue levels of ATP, phosphocreatine, and lactate in regions with altered glucose consumption. By determining the uptake of [ 14 C] deoxyglucose in the same regional samples analyzed for metabolite content, it was possible to correlate variations in glucose utilization directly with anaerobic perturbations of metabolite levels. MethodsCats of either sex weighing between 3.5 and 4.0 kg were anesthetized with pentobarbital (40 mg/kg of body weight), immobilized with gallamine, and ventilated mechanically with 30% O a and 70% N 3 . Arterial blood gases were measured at predetermined intervals and arterial pressure was monitored continuously via femoral catheters. Arterial Pco a was maintained between 31 and 34 torr by adjusting respiratory rate and volume. Rectal temperature was held at 37°C with a servo-controlled heat lamp. The EEG was recorded from 2 pairs of brass electrodes which were screwed into the skull bilaterally over the ectosylvian gyri.The left middle cerebral artery was exposed via a transorbital approach. 8 The artery was occluded with a miniature Mayfield clip in 8 animals; 2 additional animals were sham-operated without occlusion. In 2 of the 8 experimental animals, arterial pressure was lowered to 90 torr by controlled hemorrhage in order to increase the degree of cerebral ischemia.At 60 At 90 min post-ischemia, the brain was frozen in situ by pouring liquid N, into a styrofoam cup placed over the intact calvarium. During 15 min of freezing, mechanical ventilation was continued and arterial pressure remained nearly normal. This technique freezes most regions of the brain without ischemic artifact 9 because deeper layers continue to be perfused until the arrival of the freezing front. The frozen brain was then sectioned in the coronal plane at 1 cm intervals with a pre-cooled saw, taking care to keep the tissue chilled with liquid N 2 .In a -30°C chamber, multiple sa...

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Section: Methodsmentioning

confidence: 99%

“…3 ' * These methods, however, do not distinguish between aerobic and anaerobic utilization of glucose. This distinction is particularly important for damaged brain in which the fraction of glucose metabolized anaerobically may be greater than normal.…”

mentioning

confidence: 99%

Correlation between glucose utilization and metabolite levels during focal ischemia in cat brain.

Welsh

Greenberg

Jones

et al. 1980

Stroke

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“…Sokoloff et al (1977) took the next big step, developing the deoxyglucose method for measuring the local metabolic rate of glucose with autoradiography. A noninvasive variation of this technique soon became applicable to human subjects with the introduction of PET (Raichle et al 1978). Resolution at cell level is now possible using cell-specific labeled compounds, such as acetate, which is unambiguously taken up by astrocytes (Waniewski and Martin 1998).…”

Section: Measuring Metabolism Toward Single-cell Readoutsmentioning

confidence: 99%

The Astrocyte: Powerhouse and Recycling Center

Weber

Barros

2015

Cold Spring Harb Perspect Biol

157

121

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Brain metabolism is characterized by fuel monodependence, high-energy expenditure, autonomy from the rest of body, local recycling, and marked division of labor between cell types. Although neurons spend most of the brain's energy on signaling, astrocytes bear the brunt of the metabolic load, controlling the composition of the interstitial fluid, supplying neurons with energy substrates and precursors for biosynthesis, and recycling neurotransmitters, oxidized scavengers, and other waste products. Outstanding questions in this field are the role of oligodendrocytes, the metabolic behavior of the different subtypes of astrocytes during development and disease, and the emerging notion that metabolism may participate directly in information processing. T he energy requirements of the central nervous system (CNS) are very high compared with those of other organs. Although the brain accounts for merely 2% of body weight, it receives 15% of cardiac output, and uses 20% of the oxygen and 25% of the glucose of the total body turnover (Magistretti 2008). A special microarchitecture has evolved to support this extreme need, in which glial cells play a central role (Fig. 1). The microvasculature consists of a complex and dense network of highly interconnected blood vessels (Weber et al. 2008;Blinder et al. 2013) to ensure adequate delivery of oxygen and glucose. Although oxygen diffuses freely into the parenchyma, glucose and other hydrophilic energy substrates are translocated across membranes via specific transporter proteins (Fig. 1). The astrocyte is a polarized cell. One set of astrocytic processes ensheaths the vasculature and a second set reaches toward the synapse, the site of highest energy demand (Harris et al. 2012). Much of the ATP produced in the brain is spent by neurons on the recovery of ion gradients challenged by postsynaptic potentials, with a smaller investment in action potentials and neurotransmitter recycling (Harris et al. 2012). Astrocytes consume considerable energy for their own needs and the cycling of metabolically relevant substances for neurons. These metabolic processes in astrocytes and neurons are the basis for brain mapping using functional magnetic resonance imaging and positron emission tomography (PET)-methods that capture local metabolism either directly or indirectly via hemodynamic changes (Magistretti 2008;Belanger et al. 2011a). Levels of energy consumption in the whole brain are almost constant. However, individual neurons can increase their consumption dramatically. For example, a striatal neuron may Overview of astrocytic metabolism. (Inset) Astrocytes (green) reside between blood vessels (red) and neurons (yellow). Neurons and oligodendrocytes (blue) are not in direct contact with vessels. Astrocytes form metabolic domains and are coupled by gap junctions, through which they exchange metabolites and ions. Energy: The main energy substrate of the brain is glucose (glc), which crosses the endothelium and enters astrocytes via the glucose transporter GLUT1. Glucose is converted b...

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“…The calculation o f C M R o ; is conceivably accessible from the data o f a sufficiently rapid PET [ 12] after a bolus inhalation o f |S0 2, with the aid o f a model describing oxygen tissular kinetics and o f a numerical analysis tech nique derived from the published method for the measurement o f regional substrate utili zation rates by emission tomography [13]. This general model deals with tracers chemi cally identical to the studied substrates, with metabolic processes in which the tracce is in a steady state during the time o f data collection and.…”

Section: Simulation O F a Modeled Determination O F C M R Nmentioning

confidence: 99%

An Introduction to the Measurement of the Cerebral Oxygen Uptake Rate by Inhalation of 15O2: Analysis of the Contribution of 15O2 and H2I5O in Brain Radioactivity

et al. 1981

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This paper introduces a model for the computation of the regional cerebral metabolic rate of oxygen from the data of cerebral regional radioactivity collected after inhalation of ¹⁵O₂. A method was devised for the differential determination of the respective contribution of radiooxygen and of radiowater in the inflow and the outflow of radioactivity in the brain after or during such on inhalation. The results demonstrate the feasability of such a model and outline some of the methodological prerequisites to be taken into account in the numerical analysis of the data.

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Measurement of Regional Substrate Utilization Rates by Emission Tomography

Cited by 72 publications

References 6 publications

Correlation between glucose utilization and metabolite levels during focal ischemia in cat brain.

Correlation between glucose utilization and metabolite levels during focal ischemia in cat brain.

The Astrocyte: Powerhouse and Recycling Center

An Introduction to the Measurement of the Cerebral Oxygen Uptake Rate by Inhalation of <sup>15</sup>O<sub>2</sub>: Analysis of the Contribution of <sup>15</sup>O<sub>2</sub> and H<sub>2</sub><sup>I5</sup>O in Brain Radioactivity

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