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Objective: Thermal injury is associated with the development of encephalopathy. The mechanism(s) for the development of this condition have not been established. In the present study, the effects of thermal injury were determined on rat brain glucose utilization (Rg), using 2-[18F]fluoro-2-deoxy-D-glucose (18FDG)., Design: Four types of studies were performed. In one group of rats, the effect of thermal injury on total rat brain glucose utilization (Rg) was determined at 6 hours, 24 hours, and 3 weeks after injury. The brains of thermally injured rats were also assayed for hexokinase and glucose-6-phosphatase activities, since these enzyme activities are responsible for the phosphorylation and dephosphorylation of the 18FDG. We also measured total body oxygen consumption in the thermally injured rats. We wanted to compare the changes produced by thermal injury on rat brain glucose utilization (Rg) with the effects produced by compounds known to modify energy metabolism and/or rat brain glucose utilization (Rg). For that reason, in a second group of rats, an inflammatory state was produced by lipopolysaccharide injection, and rat brain glucose utilization (Rg) was determined. In the third group of rats, overall metabolism in rats was reduced by pentobarbital injection, followed by hypothermia, and rat brain glucose utilization (Rg) was determined. In the fourth group of rats, overall metabolism in rats was stimulated by 2,4-dinitrophenol injection, and rat brain glucose utilization (Rg) was determined., Materials and Methods: Glucose utilization (Rg) by the brains of these treated rats was determined using 18FDG. Oxygen consumption in vivo, as well as glucose-6-phosphatase and hexokinase activity in vitro, were measured by standard procedures., Measurements and Main Results: Glucose utilization (Rg) by rat brain was significantly reduced (p < 0.01) at 6 and 24 hours after injury, but returned to normal values 3 weeks after injury. These reductions were associated with decreases in rat brain hexokinase activity, increases in rat brain glucose-6-phosphatase activity, and decreased oxygen consumption by rats in vivo. Pentobarbital injection followed by hypothermia reduced rat brain glucose utilization (Rg) (p < 0.01), while 2,4-dinitrophenol treatment elevated rat brain glucose utilization (Rg) (p < 0.01). In contrast, LPS treatment had no effect on rat brain glucose utilization (Rg)., Conclusions: These data indicate that thermal injury decreases glucose utilization (Rg) in rat brain during the hypometabolic phase. This effect can be explained, at least in part, by alterations in hexokinase and glucose-6-phosphatase activities, as well as reductions in oxygen consumption. Thus, the changes in brain glucose utilization (Rg) appear to be associated with the ebb phase of the thermal injury. The present results observed in burned rats may provide evidence to explain the encephalopathy observed in burned patients.

We have developed a computational technique suitable for registration of sets of image data covering the whole brain volume which are translated and rotated with respect to one another. The same computational method may be used to register pairs of tomographic brain images which are rotated and translated in the transverse section plane. The technique is based on the classical theory of rigid bodies, employing as its basis the principal axes transformation. The performance of the method was studied by simulation and with image data from PET, XCT, and MRI. It was found that random errors in determining the brain contour are well tolerated. Progressively coarser axial sampling of data sets led to some degradation, but acceptable performance was obtained with axial sampling distances up to 10 mm. Given adequate digital sampling of the object volume, we conclude that registration by the principal axes transformation can be accomplished with typical errors in the range of approximately 1 mm. The advantages of the technique are simplicity and speed of computation.

A patient with major neurological deficits 5 years after a left cerebral infarction underwent correlative EEG, MRI and PET studies of cerebral blood flow and oxygen metabolism. The EEG showed abnormal slow electroencephalographic activity in the frontopolar region. The intracranial location of the slow electrical activity was estimated, as an equivalent current dipole, by using a newly developed dipole tracing (DT) method. The DT analysis showed that the dipole equivalent of the slow wave is approximately located at the frontal part of the left cingulate gyrus, away from the margins of the infarction and enlarged left lateral ventricle demonstrated by MRI, and in a region with intact oxygen consumption rate. The genesis of the slow wave is discussed.

Some sources of error in the equilibrium inhalation method for the measurement of oxygen extraction fraction and CMRO2 by positron emission computed tomography scanning have been evaluated by computer simulation. Emphasis has been placed on errors that have not been thoroughly studied in past work. These include effects of random statistical errors, systematic errors in arterial blood radioactivity concentrations, and errors due to perturbations of the equilibrium state, to tissue inhomogeneity, and to subject motion.

The 11CO2 method for measuring local brain pH with positron emission tomography (PET) has been experimentally evaluated, testing the adequacy of the kinetic model and the ability of the method to measure changes in brain pH. Plasma and tissue time/activity curves measured during and following continuous inhalation of 11CO2 were fit with a kinetic model that includes effects of tissue pH, blood flow, and fixation of CO2 into compounds other than dissolved gas and bicarbonate ions. For each of ten dogs, brain pH was measured with PET at two values of PaCO2 (range 21-67 mm Hg). The kinetic model fit the data well during both inhalation and washout of the label, with residual root mean square (RMS) deviations of the model from the measurements consistent with the statistical quality of the PET data. Brain pH calculated from the PET data shows a linear variation with log(PaCO2). These results were in good agreement with previously reported measurements of brain pH, both in absolute value and in variation with PCO2. The interpretation of these pH values in normal and pathological states is discussed.

Regional brain physiology was investigated in 11 normal resting right-handed subjects using positron emission tomography. Cerebral blood flow was studied in all subjects. Cerebral oxygen metabolism was studied in six subjects, and cerebral glucose metabolism was also studied in one subject. In five subjects, physiological activity was higher in left frontotemporal regions than right. These findings may be related to structural cerebral asymmetries or to activation of brain language centers.

We have examined the feasibility of measuring local brain pH in vivo with 11CO2 and positron emission tomography. In particular, we have addressed two objections that have been raised against this method: the assumed need to estimate local tissue PCO2 and the rapid fixation of 11C in tissue. From a reexamination of the basic theory, we argue that after administration of 11CO2 the time-dependent distribution of 11C between tissue and blood is independent of the distribution of CO2 already in the body, making it unnecessary to estimate local tissue PCO2. Assuming that the blood--brain barrier is impermeable to bicarbonate ions, there will be equal partial pressures of 11CO2 in blood and tissue at equilibrium. To overcome the problem of fixation in the tissue we have developed a kinetic model of the time-dependent distribution of 11C that accounts for regional variations in blood flow, CO2 extraction, pH, and rate of fixation. The values of the model parameters can be estimated from sequential measurements of tissue activity concentration during administration of 11CO2. Tissue pH can then be calculated from one of the parameter values, a measurement of arterial pH, and known constants. Numerical calculations based on the kinetic model with assumed values of the parameters were used to optimize the experimental design. The calculations show that problems with fixation are much less severe with continuous infusion of activity than with bolus administration. During infusion the tissue curve depends strongly on tissue pH but only weakly on the rate of fixation.(ABSTRACT TRUNCATED AT 250 WORDS)

A practical method has been developed that, using 11CO2 and positron emission tomography (PET), computes and maps (a) "effective pH" (pHt), a weighted average of intra- and extracellular pH, and (b) "clearance" (K1), product of blood flow and 11CO2 extraction. This method, together with measurements of cerebral blood flow (CBF) and oxygen extraction fraction (OEF), was applied to 12 patients with cerebral ischemia or stroke. The regional K1 was positively correlated with CBF (n = +0.78). The k1/CBF ratio, representing the extraction fraction ratio of 11CO2 to H2 15O, was negatively correlated with CBF (r = -0.54), suggesting that 11CO2 extraction decreases as flow increases. In five acute stroke patients within 2 days of onset, the injured cortex had lower CBF (20.6 ml/min/100 g), higher OEF (78.1%), and lower pHt (6.96) than the contralateral cortex (CBF = 41.4 ml/min/100 g, OEF = 53.3%, pHt = 7.00), suggesting intracellular acidosis with intact cell membranes. In three stroke patients 5-8 days after onset, the injured cortex had higher CBF (60.9 ml/min/100 g), lower OEF (32.0%), and higher pHt (7.12) than the contralateral cortex (CBF = 45.3 ml/min/100 g, OEF = 58.0%, pHt = 7.06), which suggested an increase in extracellular volume compartment reflecting loss of cell membrane integrity. This method provides information on the regional tissue acid-base status and cell membrane integrity, which may be prognostic of tissue viability.