Noninvasive determination of local cerebral metabolic rate of glucose in man

Huang, Sung‐Cheng; Phelps, Michael E.; Hoffman, Edward J.; Sideris, K.; Selin, Carl; Kuhl, David E.

doi:10.1152/ajpendo.1980.238.1.e69

“…This large difference is surprising, but, on the other hand, an earlier value of 15.3 (re calculated with LC = 0.52) reported for the same scanner (Huang et al, 1980) but using 2 to 3-cm2 regions of interest, is more comparable, being only 11% greater than the present values. We suspect that the use of anatomical atlases by Mazziotta et al to determine regions of interest may have led to a large partial volume error in the white matter measurements.…”

Section: Comparison With Previous Petcontrasting

confidence: 85%

Human Cerebral Glucose Metabolism Determined by Positron Emission Tomography: A Revisit

Brooks¹,

Hatazawa²,

Chiro³

et al. 1987

J Cereb Blood Flow Metab

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Summary:The cerebral glucose utilization rate was studied for 27 normal volunteers with 18F-deoxyglucose positron emission tomography (PET). The scanner has a spatial resolution of 6-7 mm and contains corrections for scatter, attenuation, and random coincidences. The lumped constant (tracer-to-glucose dynamic uptake ratio) was determined by comparing the average global uptake of tracer in representative slices with average glucose utilization rates measured by the Kety-Schmidt method as reported in the literature. The resulting value of 0.50 is in excellent agreement with a recent direct determination done by arterial and jugular bulb blood sampling. GrayThe use of 14C-radiolabeled deoxy glucose to de termine local glucose metabolic rates in laboratory animals was introduced by Sokoloff et aI. (1977), using autoradiographic methods that permit a clear definition of gray and white matter structures in the brain and accurate quantification of the radioactive uptake. This technique was applied by Kennedy et aI. (1978) to measure local glucose utilization rates in the brain of the macaque monkey, and was also modified for use in humans using 18F-deoxyglucose (FDG) and positron emission tomography (PET) (Phelps et aI., 1979; Reivich et aI., 1979). Unfortu nately, PET scanning suffers from serious instru mental problems, such as limited spatial resolution and gamma-ray scatter and attenuation (Hoffman et aI., 1979; Mazziotta et aI., 1981b; Bergstrom et aI., 1983). Consequently, glucose utilization rates mea sured with the first manufactured PET scanner (Huang et aI., 1980; Mazziotta et aI., 1981a) Received December 11, 1986; accepted February 18, 1987. Address correspondence and reprint requests to Dr. R. A. Brooks at Bldg. 10, Room IC451, National Institutes of Health, Bethesda, MD 20892, U. S.A.Abbreviations used: FDG, 18F-deoxyglucose; FWHM, full width at half-maximum; PET, positron emission tomography. 427and white matter values of glucose utilization in various areas of the brain were determined by placing small re gions of interest over various cortical, basal, and white matter structures. These values are within 20% of pub lished auto radiographic data on the macaque monkey. The average ratio of gray to white glucose utilization was 2.9, compared with a range of 3-5 for the monkey study and 1.6-2.2 reported in previous PET studies. The effect of instrumental errors on the results is analyzed and dis cussed. Key Words: Cerebral metabolism-Glucose Metabolism-Positron.showed a gray-to-white ratio of �2: 1, compared with >4: 1 in the autoradiographic studies. Recent improvements in PET instrumentation (e.g., Litton et aI., 1984; Brooks et aI., 1985; Hoffman et aI., 1985) have reduced the instrumentational errors and should make possible a more precise determi nation of human cerebral glucose metabolism.Another source of concern in measuring glucose metabolism with FDG is the lumped constant LC (Sokoloff et aI., 1977), which is a measure of the relative dynamic uptake of FDG and glucose. Various values ...

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“…

Summary: Measurement of the local cerebral metabolic rate of glucose (LCMRGlc) with the fluorodeoxyglucose (FDG) method requires the utilization of appropriate val ues for the rate constants of the transport and phosphor ylation 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 The deoxyglucose method originally developed by Sokoloff et aL (1977) and applied to humans by Reivich et aL (1979), Phelps et aL (1979), andHuang et aL (1980) provides a measurement of the local cerebral metabolic rate of glucose (LCMRGlc). The Sokoloff model, as modified by Phelps et aL (1979) and Huang et aL (1980), requires the rate constants kl* and k2* for forward and reverse membrane transport of fluorodeoxyglucose (FDG), and k3* and k4* for phosphorylation of FDG and dephosphory lation of FDG-6-P04' Prior investigations have demonstrated that in altered states of metabolism, values obtained for LCMRGlc can be in error if inappropriate rate constants are used (Hawkins et aI., 1981; Huang et aI., 1981 may occur, although the most significant errors occur in hypo metabolic states.

Several investigators have demonstrated a de cline in the rate of human cerebral glucose metabo lism (CMRGlc) as a function of age, using inert gas clearance methods for measuring flow and cal culating glucose metabolism as the product of cere bral blood flow (CBF) and cerebral A-V glucose difference (Dastur et aI., 1963; Gottstein et aI., 1971;Gottstein and Held, 1979).

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mentioning

confidence: 99%

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

Hawkins¹,

Mazziotta

²

,

Phelps³

et al. 1983

J Cereb Blood Flow Metab

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Summary: Measurement of the local cerebral metabolic rate of glucose (LCMRGlc) with the fluorodeoxyglucose (FDG) method requires the utilization of appropriate val ues for the rate constants of the transport and phosphor ylation 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 The deoxyglucose method originally developed by Sokoloff et aL (1977) and applied to humans by Reivich et aL (1979), Phelps et aL (1979), andHuang et aL (1980) provides a measurement of the local cerebral metabolic rate of glucose (LCMRGlc). The Sokoloff model, as modified by Phelps et aL (1979) and Huang et aL (1980), requires the rate constants kl* and k2* for forward and reverse membrane transport of fluorodeoxyglucose (FDG), and k3* and k4* for phosphorylation of FDG and dephosphory lation of FDG-6-P04' Prior investigations have demonstrated that in altered states of metabolism, values obtained for LCMRGlc can be in error if inappropriate rate constants are used (Hawkins et aI., 1981; Huang et aI., 1981 may occur, although the most significant errors occur in hypo metabolic states.Several investigators have demonstrated a de cline in the rate of human cerebral glucose metabo lism (CMRGlc) as a function of age, using inert gas clearance methods for measuring flow and cal culating glucose metabolism as the product of cere bral blood flow (CBF) and cerebral A-V glucose difference (Dastur et aI., 1963; Gottstein et aI., 1971;Gottstein and Held, 1979). Kuhl et aL (1982) made similar observations with positron tomogra phy and the FDG method. We evaluated the rate constants in order to determine whether the ob served decline in metabolism actually reflects a change in rate constants and to search for any selective alteration in the transport or phosphoryla tion processes as a function of age. MATERIALS AND METHODSEight neurologically normal volunteers, 7 males and 1 female. were studied. Their ages were 18, 21, 28, and 32 (group I) and 53, 58, 63, and 68 (group 11).All subjects were given 10 mCi [18F]FDG i.v. and scanned with a N euroECA T positron tomograph (image resolution 11.7 x 11. 7 mm FWHM in plane and 13. 4 mm axially, in the operating mode employed in this study)

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“…K 1 is the transport rate from plasma to brain tissue with units ml/100g/minute, k 2 is the transport rate back from brain to blood vessel with units 1/minute, k 3 is the phosphorylation rate of intra-cellular FDG by hexokinase enzymes to FDG-6-phosphate with units 1/minute. Because the scanning interval 60 minutes is relatively small, it will be difficult to accurately estimate the dephosphorylation rate of intra-cellular FDG-6-phosphate back to FDG, k 4 , [17]. We thus set k 4 , which is itself small, to zero.…”

Section: An Algorithm For Recovering the Input Functionmentioning

confidence: 99%

“…The bounds used are based on experimental results [17] for both gray and white matter from 13 but with doubling of upper bounds and halving of lower bounds such that the feasible space is not too conservatively estimated. Time delay between the TTACs and the input function is removed by automatically shifting the TTACs such that the first peak of each is aligned with v τp .…”

Section: An Algorithm For Recovering the Input Functionmentioning

confidence: 99%

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An input function estimation method for FDG-PET human brain studies

Guo

¹

,

Renaut

²

,

Chen

³

2007

Nuclear Medicine and Biology

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Introduction: A new model for an input function for human [ 18 F]-2-Deoxy-2-fluoro-D-glucose fluoro (FDG) positron emission tomography (PET) brain studies with bolus injection is presented. Methods:Input data for early time, roughly up to 0.6 minutes, are obtained non-invasively from the time activity curve measured from a carotid artery region of interest (CA-ROI). Representative tissue time activity curves are obtained by clustering the output curves to a limited number of dominant clusters. Three venous plasma samples at later time are used to fit the functional form of the input function in conjunction with obtaining kinetic rate parameters of the dominant clusters,K 1 , k 2 and k 3 using the compartmental model for FDG-PET. Experiments to test the approach use data from 18 healthy subjects. Results:The model provides an effective means to recover the input function in FDG-PET studies. Weighted nonlinear least squares parameter estimation using the recovered input function, as contrasted with use of plasma samples, yields highly correlated values of K =K 1 k 3 /(k 2 + k 3 ) for simulated data, correlation coefficient .99780, slope 1.019 and intercept almost zero. The estimates of K for real data by graphical Patlak analysis using the recovered input function are almost identical to those obtained using arterial plasma samples with correlation coefficients greater than 0.9976, regression slopes between .958 and 1.091 and intercepts that are virtually zero. Conclusions:A reliable semi-automated alternative for input function estimation which uses image-derived data augmented with 3 plasma samples is presented and evaluated for FDG-PET human brain studies.

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Noninvasive determination of local cerebral metabolic rate of glucose in man

Cited by 523 publications

References 19 publications

Human Cerebral Glucose Metabolism Determined by Positron Emission Tomography: A Revisit

Human Cerebral Glucose Metabolism Determined by Positron Emission Tomography: A Revisit

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

An input function estimation method for FDG-PET human brain studies

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