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.

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).

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 Estimation of Local Cerebral Glucose Utilization by Positron Emission Tomography of [18F]2-Fluoro-2-Deoxy-D-Glucose: A Critical Appraisal of Optimization Procedures

1985 ◽  
Vol 5 (1) ◽  
pp. 115-125 ◽  
Author(s):  
K. Wienhard ◽  
G. Pawlik ◽  
K. Herholz ◽  
R. Wagner ◽  
W.-D. Heiss
Keyword(s):  
Positron Emission Tomography ◽  
Metabolic Rate ◽  
Rate Constants ◽  
Glucose Utilization ◽  
Emission Tomography ◽  
Local Cerebral Glucose Utilization ◽  
Ischemic Lesion ◽  
Tracer Injection ◽  
Cerebral Glucose Utilization ◽  
Positron Emission

Various approaches estimating local cerebral glucose utilization by positron emission tomography of labeled deoxyglucose are compared. Autoradiographic methods that predict the glucose utilization rate from a single scan are unreliable in pathologic tissue because of abnormal values of the model rate constants. A normalization procedure using the ratio of measured tissue activity to activity calculated with standard rate constants is proposed to readjust the values of the rate constants. Reliable estimates of metabolic rates can be obtained from dynamic recordings of tracer uptake. In the graphic approach, metabolic rate can be derived from the slope of a segment of a transformed uptake curve, which becomes linear at 15–20 min after intravenous tracer injection, with an accuracy comparable with that in complete dynamic studies. However, by recording and analyzing full-length uptake curves, in addition to metabolic rate, the model rate constants can be determined regionally. The physiological significance of those parameters is demonstrated in crossed cerebellar deactivation in 30 patients with supratentorial infarcts. Mild hypometabolism both within the ischemic lesion and in the morphologically intact cerebellum is accompanied by a reduction of the phosphorylation rate only. Severe metabolic depression, by contrast, affects both cerebellar transport and phosphorylation processes, whereas in the cerebrum, only the rate constant k1 is significantly correlated with the degree of metabolic disturbance.

scholarly journals Tomographic Mapping of Kinetic Rate Constants in the Fluorodeoxyglucose Model Using Dynamic Positron Emission Tomography

1986 ◽  
Vol 6 (4) ◽  
pp. 447-454 ◽  
Author(s):  
Hiroshi Sasaki ◽  
Iwao Kanno ◽  
Matsutaro Murakami ◽  
Fumio Shishido ◽  
Kazuo Uemura
Keyword(s):  
Rate Constants ◽  
Glucose Utilization ◽  
Least Squares Method ◽  
Computing Time ◽  
Kinetic Rate ◽  
Positron Emission ◽  
Kinetic Rate Constants ◽  
Low Glucose ◽  
Tomographic Mapping ◽  
Phosphorylation Rate

A quick computing algorithm to calculate the rate constants ( k*1, k*2, k*3) in the [18F]2-fluoro-2-deoxy-d-glucose (FDG) model was developed. The algorithm solved for the rate constants pixel by pixel using a conventional least-squares method and two tables consisting of a set of various rate constants, to shorten the computing time. Five planes of rate constant images were obtained. A combined study using the dynamic FDG method and the 15O-labeled gas continuous inhalation method was performed on seven healthy male volunteers aged 26–35 years. Results indicated an apparent discrepancy between CMRglu and CMRO2 in the cerebellum, where the low glucose utilization was correlated with a low FDG phosphorylation rate ( k*3) despite a sufficient FDG transportation rate ( k*1) from plasma to tissue.

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 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 and progression of illness in Alzheimer's disease

1995 ◽  
Vol 10 (8) ◽  
pp. 659-667 ◽  
Author(s):  
Benjamin V. Siegel ◽  
Monte S. Buchsbaum ◽  
Arnold Starr ◽  
Richard C. Mohs ◽  
Dirceu C. Neto
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Metabolic Rate ◽  
Glucose Metabolic Rate
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