A method has been developed for the simultaneous measurement of the rates of glucose consumption in the various structural and functional components of the brain in vivo. The method can be applied to most laboratory animals in the conscious state. It is based on the use of z -d e o x y -~ ['4C]glucose (['4C]DG) as a tracer for the exchange of glucose between plasma and brain and its phosphorylation by hexokinase in the tissues. [14C]DG is used because the label in its product, [ '4C]deoxyglucose-6-phosphate, is essentially trapped in the tissue over the time course of the measurement. A model has been designed based on the assumptions of a steady state for glucose consumption, a first order equilibration of the free [14C]DG pool in the tissue with the plasma level, and relative rates of phosphorylation of [14C]DG and glucose determined by their relative concentrations in the precursor pools and their respective kinetic constants for the hexokinase reaction. An operational equation based on this model has been derived in terms of determinable variables. A pulse of [14C]DG is administered intravenously and the arterial plasma [ 14C]DG and glucose concentrations monitored for a preset time between 30 and 45min. At the prescribed time, the head is removed and frozen in liquid N,-chilled Freon XII, and the brain sectioned for autoradiography. Local tissue concentrations of ['4C]DG are determined by quantitative autoradiography. Local cerebral glucose consumption is calculated by the equation on the basis of these measured values.The method has been applied to normal albino rats in the conscious state and under thiopental anesthesia. The results demonstrate that the local rates of glucose consumption in the brain fall into two distinct distributions, one for gray matter and the other for white matter. In the conscious rat the values in the gray matter vary widely from structure to structure (54-197pmo1/100g/min) with the highest values in structures related to auditory function, e.g. medial geniculate body, superior olive, inferior colliculus, and auditory cortex. The values in white matter are more uniform (i.e. 33-40 pmo1/100 g/min) at levels approximately one-fourth to one-half those of gray matter. Heterogeneous rates of glucose consumption are frequently seen within specific structures, often revealing a pattern of cytoarchitecture. Thiopental anesthesia markedly depresses the rates of glucose utilization throughout the brain, particularly in gray matter, and metabolic rate throughout gray matter becomes more uniform at a lower level THE MAMMALIAN brain is a complex heterogeneous organ comprising many structural and functional components with different and independently regulated levels of functional activity and energy metabolism. Much of our present knowledge of cerebral .

ABSTRACT[14C]deoxyglucose-6-phosphate, the fractional turnover rate of the free [14C]deoxyglucose pool in the tissue, and the ratios of the Michaelis-Menten kinetic constants of hexokinase for deoxyglucose and glucose (6). The key to the localization possible with the method is a quantitative autoradiographic technique for the measurement of local tissue concentrations of ['4C]deoxyglucose-6-phosphate. Even without the quantification, however, the autoradiographs are themselves pictorial representations of the local rates of glucose consumption throughout the brain. Inasmuch as local energy metabolism in the brain, as in other tissues, is closely coupled to'local functional activity, the method has proved effective for the delineation of local cerebral regions with altered functional activity in response to experimentally modified physiological states (7).The binocular visual system of the monkey appeared to offer an appropriately intricate METHODSRhesus monkeys of either sex weighing 2.5-3.5 kg were used in these studies. Polyethylene catheters were inserted in a femoral artery and vein after light halothane and nitrous oxide anesthesia, and the animals were then placed in a restraining chair and allowed to recover from the anesthesia for at least 4 hr. The experimental period was initiated by the intravenous injection of a pulse of 100 ,uCi/kg of ['4C]deoxyglucose (specific activity, 50-55 mCi/mmol; New England Nuclear Corp., Boston, Mass.) contained in 3 ml of normal saline. In most of the animals, timed arterial blood samples were drawn during the ensuing 45 min period for the measurement of the arterial 4230

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The 2-deoxy-D-[¹⁴C]-glucose method for the quantitative determination of local cerebral glucose utilization has been applied to the mouse. The experiments were conducted in awake freely moving animals. Local cerebral glucose utilization was found to vary widely throughout the brain with the lowest values in white matter and the highest in gray matter. The most metabolically active structures were those involved in auditory function or in general motor activity. All the values were lower than those observed previously in the conscious rat. The use of free-moving animals may be of importance since it allows the study of physiological or pathological behavioral states.

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