scholarly journals Effect of Ischemia on Quantification of Local Cerebral Glucose Metabolic Rate in Man

1981 ◽  
Vol 1 (1) ◽  
pp. 37-51 ◽  
Author(s):  
Randall A. Hawkins ◽  
Michael E. Phelps> ◽  
Sung-Cheng Huang ◽  
David E. Kuhl
Keyword(s):  
Glucose Metabolism ◽  
Metabolic Rate ◽  
Rate Constants ◽  
Normal Values ◽  
Cerebral Glucose Metabolism ◽  
Stroke Rate ◽  
Metabolic Rates ◽  
Lumped Constant ◽  
Glucose Metabolic Rate ◽  
The Stability

The model for quantifying local cerebral glucose metabolic rates originally developed by Sokoloff et al. and modified by Phelps, Huang and co-workers was applied to humans with cerebral ischemia (i.e., stroke). Rate constants for fluorodeoxyglucose were measured in ischemic and nonischemic regions with positron computed tomography. Using measured rate constants for ischemia, the model generates more accurate estimates of local cerebral glucose metabolism as compared to the use of rate constants from normal young adults, because the local metabolic rate is significantly underestimated, and temporal instability of the model is observed when normal values are applied to ischemic regions. A method was also developed to test the stability of the local lumped constant. The estimates of the lumped constant showed no or only small variations between ischemic and nonischemic types. Thus, errors introduced in the calculated local cerebral glucose metabolism by inappropriate rate constants appear to be more significant than those caused by any potential change in the lumped constant in ischemia.

scholarly journals Glucose Metabolic Rate Kinetic Model Parameter Determination in Humans: The Lumped Constants and Rate Constants for [18F]Fluorodeoxyglucose and [11C]Deoxyglucose

1985 ◽  
Vol 5 (2) ◽  
pp. 179-192 ◽  
Author(s):  
M. Reivich ◽  
A. Alavi ◽  
A. Wolf ◽  
J. Fowler ◽  
J. Russell ◽  
...  
Keyword(s):  
Kinetic Model ◽  
Metabolic Rate ◽  
Rate Constants ◽  
Glucose Consumption ◽  
Normal Subjects ◽  
Parameter Determination ◽  
Metabolic Rates ◽  
Mean Values ◽  
Glucose Metabolic Rate ◽  
The Mean

The rate constants and lumped constants (LCs) for [18F]fluorodeoxyglucose ([18F]FDG) and [11C]deoxyglucose ([11C]DG) were determined in humans for the glucose metabolic rate kinetic model used to measure local cerebral glucose consumption. The mean values (±SE) of the LCs for [18F]FDG and [11C]DG are 0.52 ± 0.028 (n = 9) and 0.56 ± 0.043 (n = 6), respectively. The mean values (±SE) of the rate constants k*1, k*2, k*3, and k*4 for [18F]FDG for gray matter are 0.095 ± 0.005, 0.125 ± 0.002, 0.069 ± 0.002, and 0.0055 ± 0.0003, respectively. The corresponding values for white matter are 0.065 ± 0.005, 0.126 ± 0.003, 0.066 ± 0.002, and 0.0054 ± 0.0006, respectively. Using these values and previously published values for the rate constants for [11C]DG, the average whole-brain metabolic rates for glucose in normal subjects measured with [18F]FDG and [11C]DG are 5.66 ± 0.37 (n = 6) and 4.99 ± 0.23 (n = 6) mg/100 g/min, respectively. These values are not significantly different ( t = 1.56, p > 0.10) and agree well with reported values in the literature determined by means of the Kety-Schmidt technique.

scholarly journals Cerebral Glucose Metabolism as a Function of Age in Man: Influence of the Rate Constants in the Fluorodeoxyglucose Method

1983 ◽  
Vol 3 (2) ◽  
pp. 250-253 ◽  
Author(s):  
Randall A. Hawkins ◽  
John C. Mazziotta ◽  
Michael E. Phelps ◽  
Sung-Cheng Huang ◽  
David E. Kuhl ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Metabolic Rate ◽  
Rate Constants ◽  
Cerebral Glucose Metabolism ◽  
Cerebral Metabolic Rate

Measurement of the local cerebral metabolic rate of glucose (LCMRGlc) with the fluorodeoxyglucose (FDG) method requires the utilization of appropriate values for the rate constants of the transport and phosphorylation processes. We measured these rate constants as a function of age to determine whether a decline in LCMRGlc as a function of age, in prior studies with the FDG method, actually represents changes in the rate constants. We found that measurements of LCMRGlc are not significantly affected by changes in rate constants as a function of aging, and that LCMRGlc did not change significantly with age.

scholarly journals Deoxyglucose Kinetics in a Rat Brain Tumor

1989 ◽  
Vol 9 (3) ◽  
pp. 315-322 ◽  
Author(s):  
Michael M. Graham ◽  
Alexander M. Spence ◽  
Mark Muzi ◽  
Gregory L. Abbott
Keyword(s):  
Rate Constants ◽  
Liquid Scintillation ◽  
Scintillation Counting ◽  
Metabolic Rates ◽  
Blood Samples ◽  
Time Points ◽  
Lumped Constant ◽  
Rat Brain Tumor ◽  
Dg Method ◽  
Dual Tracer

Accurate quantitation of local glucose metabolic rates (LMRglc) of abnormal tissues such as brain tumors with the 2-deoxyglucose (DG) method requires knowledge of the tissue rate constants and lumped constant. The deoxyglucose rate constants were measured in an experimental intracerebral glioma in 24 awake rats with a dual tracer [(3H)-DG and (14C)-DG] method. Tissue time points were obtained at 2, 5, 10, 18, 30, 60, 90, and 180 min after injection by decapitation and liquid scintillation counting. Blood samples were obtained at 1 min intervals initially and at longer intervals later. The rate constants were estimated with parameter estimation. LMRglc was calculated from the rate constants, assuming a lumped constant of 0.5. K1 for normal cerebrum was found to be 0.258 ml/g/min, and k2– k4 were 0.406, 0.075, and 0.0103 min−1; LMRglc = 65.1 μ;mol/100 g/min. The corresponding values for the glioma were 0.108, 0.126, 0.040, and 0.0019 with LMRglc = 41.7. The considerably lower k4 in the glioma was reflected in persistent higher activity in the glioma at longer times. Thus, tissue activity alone cannot be used to assess relative glucose metabolic rates in abnormal tissues such as gliomas, particularly at late times after injection.

Measurement of regional glucose metabolic rates in reperfused myocardium

1991 ◽  
Vol 261 (6) ◽  
pp. H2058-H2068 ◽  
Author(s):  
D. B. Buxton ◽  
H. R. Schelbert
Keyword(s):  
Metabolic Rate ◽  
Glucose Utilization ◽  
Plasma Free Fatty Acid ◽  
Balloon Occlusion ◽  
Normal Myocardium ◽  
Metabolic Rates ◽  
Fdg Uptake ◽  
Positron Emission ◽  
Glucose Metabolic Rate ◽  
Anesthetized Dogs

Regional myocardial glucose utilization was measured with [18F]fluorodeoxyglucose (FDG) and positron emission tomography in normal and postischemic tissue after 3 h of intracoronary balloon occlusion in closed-chest chronically instrumented anesthetized dogs. Estimates of glucose metabolic rates were made using the Sokoloff model, assuming the lumped constant to be unchanged in reperfused tissue. Myocardial sectors were classified as normal, reversibly injured, or infarct containing based on occlusion blood flow images and postmortem histology. Occlusion flow, measured by microspheres, was reduced by 38% in reversibly injured and 74% in infarct-containing sectors, recovering to 91 and 66%, respectively, 1 h postreperfusion. One month postreperfusion, flow was normal in reversibly injured sectors but remained depressed at 60% in infarct-containing sectors. Glucose utilization at baseline was homogeneous, averaging 0.8 mumol.g-1.min-1. After 3 h of reperfusion following occlusion of the left anterior descending coronary artery, regional glucose metabolic rate was increased 60% relative to baseline in normal myocardium but not in postischemic sectors, leading to an enhancement of FDG uptake in normal relative to postischemic myocardium. At 24 h postreperfusion, the glucose metabolic rate decreased in normal remote tissue to 46% of baseline levels, probably reflecting increased plasma free fatty acid levels, but was not significantly altered in reversibly injured myocardium, leading to enhanced FDG uptake in reversibly injured relative to normal myocardium. Subsequently, glucose metabolism in normal and postischemic sectors was not significantly different. Prolonged relative enhancement of glucose metabolic rate in postischemic tissue was found when the glucose metabolic rate in normal myocardium was low. Myocardial glucose utilization correlated with hg, the rate constant for FDG phosphorylation under all conditions (r = 0.88).

Acute effects of insulin-like growth factor I and insulin on glucose metabolism in vivo

1990 ◽  
Vol 259 (4) ◽  
pp. E561-E567 ◽  
Author(s):  
R. T. Moxley ◽  
P. Arner ◽  
A. Moss ◽  
A. Skottner ◽  
M. Fox ◽  
...  
Keyword(s):  
Growth Factor ◽  
Glucose Metabolism ◽  
Metabolic Rate ◽  
Glucose Uptake ◽  
Whole Body ◽  
Hepatic Glucose ◽  
Igf I ◽  
Glucose Metabolic Rate ◽  
Stimulation Of

We have compared the actions of insulin-like growth factor (IGF-I) and insulin on glucose metabolism in vivo, using the glucose clamp technique in rats. Both hormones caused dose-dependent inhibition of hepatic glucose production, stimulation of whole body glucose disposal, and an increase in the glucose metabolic rate of specific muscles. Infusion of IGF-I also decreased the plasma concentration of insulin. An an infusion rate of 0.57 nmol.kg-1.min-1, IGF-I led to stimulation of whole body glucose uptake that was similar to the glucose uptake produced by infusion of 0.01 nmol.kg-1.min-1 insulin. The glucose metabolic rate, as measured by 2-deoxy-D-glucose uptake, was comparable in quadriceps femoris, soleus, and diaphragm muscles during the infusion of 0.57 nmol.kg-1.min-1 IGF-I and 0.01 nmol.kg-1.min-1 insulin. However, at these rates of infusion, IGF-I caused only a 38 +/- 6% inhibition of hepatic glucose output compared with 66 +/- 12% inhibition by insulin (P less than 0.05). Thus, under these conditions, muscle is more responsive than liver to IGF-I, which agrees with the complement of IGF-I receptors in the two tissues.

Fluorodeoxyglucose rate constants, lumped constant, and glucose metabolic rate in rabbit heart

1987 ◽  
Vol 252 (4) ◽  
pp. H777-H787 ◽  
Author(s):  
J. Krivokapich ◽  
S. C. Huang ◽  
C. E. Selin ◽  
M. E. Phelps
Keyword(s):  
Metabolic Rate ◽  
Rate Constant ◽  
Rate Constants ◽  
Interventricular Septum ◽  
Hydrolysis Rate ◽  
Constant Infusion ◽  
Coincidence Counting ◽  
Paired Stimuli ◽  
Lumped Constant ◽  
Phosphorylation Rate

The isolated arterially perfused rabbit interventricular septum was used to measure myocardial metabolic rate for glucose (MMRGlc) and rate constants and lumped constant (LC) for the glucose analogue [18F]fluorodeoxyglucose (FDG) using a tracer kinetic model. FDG was delivered by constant infusion during coincidence counting of tissue 18F radioactivity. The MMRGlc was measured by the Fick method. Control septa were paced at 72 beats/min and perfused at 1.5 ml/min with oxygenated perfusate containing 5.6 mM glucose and 5 mU/ml insulin. The following conditions were tested: 3.0 and 4.5 ml/min; insulin increased to 25 mU/ml; insulin omitted; 2.8 mM and 11.2 mM glucose; 144 beats/min and 96 paired stimuli/min; and anoxia. Under all conditions studied the phosphorylation (hexokinase) reaction was rate limiting relative to transport. Compared with control conditions, the phosphorylation rate constant was significantly increased with 2.8 mM glucose as well as in anoxia. With 4.5 ml/min and 11.2 mM glucose, conditions that should increase glucose flux into tissue without increasing demand, the phosphorylation rate constant decreased significantly. With 11.2 mM glucose, 96 paired stimuli/min, and anoxia without insulin, a significant increase in the hydrolysis rate of FDG 6-phosphate was observed and suggests that hydrolysis is also an important mechanism for regulating the MMRGlc. Increased transport rate constants were observed with increased flow rates, 96 paired stimuli/min, and anoxia at 96 beats/min. The LC was not significantly different from control in 11 of 14 conditions studied. Therefore, under most conditions, an average LC can be used to calculate MMRGlc estimates.

scholarly journals Alternative Approach to Single-Scan Estimation of Cerebral Glucose Metabolic Rate Using Glucose Analogs, with Particular Application to Ischemia

1984 ◽  
Vol 4 (1) ◽  
pp. 35-40 ◽  
Author(s):  
G. D. Hutchins ◽  
J. E. Holden ◽  
R. A. Koeppe ◽  
J. R. Halama ◽  
S. J. Gatley ◽  
...  
Keyword(s):  
Metabolic Rate ◽  
Linear Relationship ◽  
Rate Constants ◽  
Glucose Utilization ◽  
Tissue Concentration ◽  
Accurate Estimation ◽  
Transport Parameter ◽  
Glucose Metabolic Rate ◽  
Time Courses ◽  
Phosphorylation Rate

In the glucose analog method for determining local glucose utilization rates, time courses of tissue and plasma radioactivity are measured and then analyzed in terms of first-order exchange of label between tissue compartments. The rate of glucose utilization is assumed to have a fixed, linear relationship to the analog phosphorylation rate calculated from the fitted rate constants. Accurate estimation of the rate constants requires many hours of dynamic data acquisition. Therefore, techniques assuming a linear relationship between analog phosphorylation rate and total tissue concentration of label were developed to predict glucose utilization rates from a single scan. Previously reported linearizations differ in their sensitivity to differences between current and average kinetic rate constants, and thus in their accuracy. We have developed a method that is insensitive to the presumed value of the blood flow–capillary wall transport parameter k1. This new single-scan approach has been validated by comparison of the single-scan metabolic rate values with the values calculated from the dynamic measurements.

Effect of Phenytoin on Human Cerebral Glucose Metabolism

1986 ◽  
Vol 6 (3) ◽  
pp. 315-320 ◽  
Author(s):  
William H. Theodore ◽  
Dikran Bairamian ◽  
Michael E. Newmark ◽  
Giovanni DiChiro ◽  
Roger J. Porter ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Glucose Metabolism ◽  
Regions Of Interest ◽  
Cerebral Glucose Metabolism ◽  
Emission Tomography ◽  
Metabolic Rates ◽  
Seizure Disorders ◽  
Positron Emission ◽  
Ictal Activity ◽  
Cortical Regions

We used serial positron emission tomography scans with [18F]2-deoxyglucose to study the effect of phenytoin on human cerebral glucose metabolism in 10 patients with seizure disorders. Local CMRglu for each patient was measured in 10 regions of interest. EEGs were performed during each procedure to match scans for state of consciousness and exclude data from scans with ictal activity. Serial scans without a drug change were performed in six control patients. Metabolic rates were significantly lower in two cortical regions while patients were taking phenytoin. No significant changes on repeat scan were seen in the control population. Measured across all regions of interest, metabolic rates were 13% higher when patients were off phenytoin (p < 0.02).

Regional Metabolism in Microsmic Patients with Schizophrenia

1991 ◽  
Vol 36 (9) ◽  
pp. 645-650 ◽  
Author(s):  
Campbell Clark ◽  
Lili Kopala ◽  
Trevor Hurwitz ◽  
David Li
Keyword(s):  
Basal Ganglia ◽  
Glucose Metabolism ◽  
Cerebral Glucose Metabolism ◽  
Metabolic Rates ◽  
Medication Regimen ◽  
Current Medication ◽  
Patient Groups ◽  
Regional Metabolism ◽  
Normal Controls

The cerebral glucose metabolism of eight patients with schizophrenia and an olfactory agnosia was compared with that of eight normosmic patients with schizophrenia and eight normal controls. Since all patients were scanned while on their current medication regimen, the duration and dosage of the medication of the two patient groups were compared. Similarly, duration and dosage were correlated with absolute regional metabolic rates. No significant effects were found in these analyses. The patients with schizophrenia had significantly lower rates of frontal metabolism than the normal controls. However, the patients with schizophrenia and an olfactory agnosia had a lower right basal ganglia and thalamic metabolism than the normosmic patients with schizophrenia.

scholarly journals Error Sensitivity of Fluorodeoxyglucose Method for Measurement of Cerebral Metabolic Rate of Glucose

1981 ◽  
Vol 1 (4) ◽  
pp. 391-401 ◽  
Author(s):  
Sung-Cheng Huang ◽  
Michael E. Phelps ◽  
Edward J. Hoffman ◽  
David E. Kuhl
Keyword(s):  
Metabolic Rate ◽  
Rate Constants ◽  
Normal Values ◽  
Weighted Average ◽  
Control Group ◽  
Kinetic Measurements ◽  
Normal Value ◽  
Cerebral Metabolic Rate ◽  
Scan Time ◽  
Metabolic Conditions

The fluorodeoxyglucose (FDG) method for the measurement of local cerebral metabolic rate of glucose (LCMRGlc) employs typical values of the FDG transport rate constants that have been obtained by kinetic measurements on an appropriate control group. Discrepancies between the true values of the rate constants in tissue and the typical values used in the operational equation of the FDG method will introduce error in the estimate of LCMRGlc. Computer simulations were used to evaluate the accuracy of the FDG method in cases where (1) the tissue LCMRGlc deviates greatly from the normal values (e.g., stroke) or (2) the tissue LCMRGlc changes during the experiment (e.g., epileptic seizure). The effects of the magnitude and duration of metabolic changes were studied. The rsults indicate that if tissue LCMRGlc differs greatly from the normal value, the error in the estimated LCMRGlc at a scan time of 60 min is less than 20% of the difference between the true and normal values. In the non-steady-state cases, the estimated LCMRGlc was found to be a weighted average of the metabolic rates during the experiments, with the weightings approximately proportional to the plasma FDG concentration at the corresponding times. For example, if LCMRGlc in tissue was 5 times the normal values for the first 10 min but then returned to normal state, the LCMRGlc measured by the FDG method at a scan time of 60 min would be about only 2–3 times the normal value. The results of this study provide a better understanding of the accuracy of the FDG method under various tissue metabolic conditions and is useful for interpreting metabolic values obtained with the FDG method.

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