Michaelis-menten constraints improved cerebral glucose metabolism and regional lumped constant measurements with [18F] fluorodeoxyglucose

Hiroto Kuwabara, Alan C. Evans, Albert Gjedde

Research output: Contribution to journalArticle

Abstract

In the three-compartment model of transfer of native glucose and [18F]fluorodeoxyglucose (FDG) into brain, both transport across the blood-brain barrier and phosphorylation by hexokinase can be described by the Michaelis-Menten equation. This permits the use of fixed transport (τ = K1*/K1) and phosphorylation (φ = k3*/k3) ratios and a common partition volume (Ve = K1/k2) for tracer and glucose. By substituting transfer constants of FDG for those of glucose, using τ and φ, the lumped constant was determined directly by positron tomography. The same constraints also eliminated k2* and k3* from the model, thus limiting the parameters to K* [equivalent to K1* k3*/(k2* + k3*)], K1*, and the cerebral vascular volume (V0). In six healthy elderly men (aged 61 ± 5 years), time-activity records of cerebral cortical regions were analyzed with τ = 1.1 and φ = 0.3. The results were compared with those of the conventional FDG method. At 20 min, the goodness of fit by the new equation was as good as that of the conventional method at 45 min. The estimates obtained by the constrained method had stable coefficients of variation. After 20 min, regional differences between the estimates were independent of time, although we observed steady decreases of K* and (k3*). The decrease strongly suggested dephosphorylation of FDG-6-phosphate, particularly after 20 min. All estimates of variable with the constrained method were more accurate than those of the conventional method, including the cerebral glucose metabolic rate itself, as well as physiologically more meaningful, particularly with respect to k2* and k3*.

Original languageEnglish (US)
Pages (from-to)180-189
Number of pages10
JournalJournal of Cerebral Blood Flow and Metabolism
Volume10
Issue number2
StatePublished - 1990
Externally publishedYes

Fingerprint

Fluorodeoxyglucose F18
Glucose
Phosphorylation
Hexokinase
Blood-Brain Barrier
Blood Vessels
Phosphates
Tomography
Electrons
Brain

Keywords

  • Cerebral metabolic rate for glucose-[f]fluorodeoxyglucose
  • Michaelis-menten equations

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Endocrinology, Diabetes and Metabolism

Cite this

@article{37a80bf4a242497f8ba8ee0fe46b3029,
title = "Michaelis-menten constraints improved cerebral glucose metabolism and regional lumped constant measurements with [18F] fluorodeoxyglucose",
abstract = "In the three-compartment model of transfer of native glucose and [18F]fluorodeoxyglucose (FDG) into brain, both transport across the blood-brain barrier and phosphorylation by hexokinase can be described by the Michaelis-Menten equation. This permits the use of fixed transport (τ = K1*/K1) and phosphorylation (φ = k3*/k3) ratios and a common partition volume (Ve = K1/k2) for tracer and glucose. By substituting transfer constants of FDG for those of glucose, using τ and φ, the lumped constant was determined directly by positron tomography. The same constraints also eliminated k2* and k3* from the model, thus limiting the parameters to K* [equivalent to K1* k3*/(k2* + k3*)], K1*, and the cerebral vascular volume (V0). In six healthy elderly men (aged 61 ± 5 years), time-activity records of cerebral cortical regions were analyzed with τ = 1.1 and φ = 0.3. The results were compared with those of the conventional FDG method. At 20 min, the goodness of fit by the new equation was as good as that of the conventional method at 45 min. The estimates obtained by the constrained method had stable coefficients of variation. After 20 min, regional differences between the estimates were independent of time, although we observed steady decreases of K* and (k3*). The decrease strongly suggested dephosphorylation of FDG-6-phosphate, particularly after 20 min. All estimates of variable with the constrained method were more accurate than those of the conventional method, including the cerebral glucose metabolic rate itself, as well as physiologically more meaningful, particularly with respect to k2* and k3*.",
keywords = "Cerebral metabolic rate for glucose-[f]fluorodeoxyglucose, Michaelis-menten equations",
author = "Hiroto Kuwabara and Evans, {Alan C.} and Albert Gjedde",
year = "1990",
language = "English (US)",
volume = "10",
pages = "180--189",
journal = "Journal of Cerebral Blood Flow and Metabolism",
issn = "0271-678X",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - Michaelis-menten constraints improved cerebral glucose metabolism and regional lumped constant measurements with [18F] fluorodeoxyglucose

AU - Kuwabara, Hiroto

AU - Evans, Alan C.

AU - Gjedde, Albert

PY - 1990

Y1 - 1990

N2 - In the three-compartment model of transfer of native glucose and [18F]fluorodeoxyglucose (FDG) into brain, both transport across the blood-brain barrier and phosphorylation by hexokinase can be described by the Michaelis-Menten equation. This permits the use of fixed transport (τ = K1*/K1) and phosphorylation (φ = k3*/k3) ratios and a common partition volume (Ve = K1/k2) for tracer and glucose. By substituting transfer constants of FDG for those of glucose, using τ and φ, the lumped constant was determined directly by positron tomography. The same constraints also eliminated k2* and k3* from the model, thus limiting the parameters to K* [equivalent to K1* k3*/(k2* + k3*)], K1*, and the cerebral vascular volume (V0). In six healthy elderly men (aged 61 ± 5 years), time-activity records of cerebral cortical regions were analyzed with τ = 1.1 and φ = 0.3. The results were compared with those of the conventional FDG method. At 20 min, the goodness of fit by the new equation was as good as that of the conventional method at 45 min. The estimates obtained by the constrained method had stable coefficients of variation. After 20 min, regional differences between the estimates were independent of time, although we observed steady decreases of K* and (k3*). The decrease strongly suggested dephosphorylation of FDG-6-phosphate, particularly after 20 min. All estimates of variable with the constrained method were more accurate than those of the conventional method, including the cerebral glucose metabolic rate itself, as well as physiologically more meaningful, particularly with respect to k2* and k3*.

AB - In the three-compartment model of transfer of native glucose and [18F]fluorodeoxyglucose (FDG) into brain, both transport across the blood-brain barrier and phosphorylation by hexokinase can be described by the Michaelis-Menten equation. This permits the use of fixed transport (τ = K1*/K1) and phosphorylation (φ = k3*/k3) ratios and a common partition volume (Ve = K1/k2) for tracer and glucose. By substituting transfer constants of FDG for those of glucose, using τ and φ, the lumped constant was determined directly by positron tomography. The same constraints also eliminated k2* and k3* from the model, thus limiting the parameters to K* [equivalent to K1* k3*/(k2* + k3*)], K1*, and the cerebral vascular volume (V0). In six healthy elderly men (aged 61 ± 5 years), time-activity records of cerebral cortical regions were analyzed with τ = 1.1 and φ = 0.3. The results were compared with those of the conventional FDG method. At 20 min, the goodness of fit by the new equation was as good as that of the conventional method at 45 min. The estimates obtained by the constrained method had stable coefficients of variation. After 20 min, regional differences between the estimates were independent of time, although we observed steady decreases of K* and (k3*). The decrease strongly suggested dephosphorylation of FDG-6-phosphate, particularly after 20 min. All estimates of variable with the constrained method were more accurate than those of the conventional method, including the cerebral glucose metabolic rate itself, as well as physiologically more meaningful, particularly with respect to k2* and k3*.

KW - Cerebral metabolic rate for glucose-[f]fluorodeoxyglucose

KW - Michaelis-menten equations

UR - http://www.scopus.com/inward/record.url?scp=0025232680&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025232680&partnerID=8YFLogxK

M3 - Article

C2 - 2303534

AN - SCOPUS:0025232680

VL - 10

SP - 180

EP - 189

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

IS - 2

ER -