Comparative Regional Analysis of 2-Fluorodeoxyglucose and Methylglucose Uptake in Brain of Four Stroke Patients. With Special Reference to the Regional Estimation of the Lumped Constant

Abstract

The glucose metabolic rate of the human brain can be measured with labeled deoxyglucose, using positron emission tomography, provided certain conditions are fulfilled. The original method assumed irreversible trapping of deoxyglucose metabolites in brain during the experimental period, and it further requires that a conversion factor between deoxyglucose and glucose, the "lumped constant," be known for the brain regions of interest. We examined the assumption of irreversible trapping of fluorodeoxyglucose metabolites in brain of four patients in 365 normal and 4 recently infarcted regions. The average net, steady-state rate of fluorodeoxyglucose (KD) accumulation in normal regions of the four patients was 0.025 ml g-1 min-1. We also examined the variability of the lumped constant. We first confirmed that methylglucose is not phosphorylated in the human brain. We then estimated the lumped constant from the regional distribution of labeled methylglucose in brain. The average (virtual) volume of distribution of labeled methylglucose in the normal regions was 0.46 ml g-1 and was the same in both gray and white matter structures. The average brain glucose content corresponding to this value was 1.3 mumol g-1, assuming a Michaelis constant (Kt) of 3.7 mM for glucose transport across the blood-brain barrier. The lumped constant varied insignificantly between 0.4 and 0.5 in most regions, with an overall average of 0.44. It did not vary significantly between the patients and was the same in gray and white matter structures, but was inversely related to the calculated metabolic rate. This observation indicates that metabolic rates calculated with a fixed lumped constant (e.g., 0.40) would be slightly underestimated at high metabolic rates and slightly overestimated at low metabolic rates. The average glucose metabolic rates of the 365 normal regions, in which gray matter regions prevailed by 20:1, was 32 mumol 100 g-1 min-1. The average glucose phosphorylation rate in white matter was 20 mumol 100 g-1 min-1 with a lumped constant of 0.45. In the recently infarcted areas, the lumped constants varied from 0.37 to 2.83, corresponding to glucose metabolic rates varying from 2 to 18 mumol 100 g-1 min-1. Two infarct types were identified. In one type, the phosphorylation-limited type, glucose content and the lumped constant were close to normal (1 mumol g-1 and 0.40, respectively). In the other, the transport/flow-limited type, the glucose content was low (0.2 mumol g-1), and the lumped constant in excess of unity. The evidence from the present study upholds the model of Sokoloff et al. in every detail.

Graphical Evaluation of Blood-to-Brain Transfer Constants from Multiple-Time Uptake Data. Generalizations

“…11 and 19 are given by intercept where the expression for Ve is similar to that de rived by Gjedde et al (1985) when there is no re versible binding.…”

“…The purpose of this article is to provide a simpler derivation of the graphical analysis technique and to discuss its potential for more general application in systems other than the study of the blood-brain barrier or deoxyglucose up take (Gjedde et al, 1985). In particular, a descrip tion of how graphical analysis can be used to ana lyze tissue uptake data alone, when blood-plasma concentrations of the test substance cannot be mea sured, is given and the conditions necessary for this analysis to be valid.…”

Neuroreceptor Assay with Positron Emission Tomography: Equilibrium versus Dynamic Approaches

“…The more general one is nonlinear regres sion [the "explicit method" referred to by Perl mutter et al (1986)], which gives the set of param eter values that minimizes the deviation between the measured kinetics and the model prediction. The other technique is the normalized graphical method (Patlak et al , 1983;Gjedde et al , 1985) [the "ratio method" referred to by Perlmutter et al (1986)], which transforms the coordinates of the tissue time-activity curve to normalized tissue ac tivity (i. e. , tissue activity divided by plasma ac tivity) versus normalized time (i. e. , J(plasma ac tivity) dt divided by plasma activity). The latter is just a particular way of representing the tissue time-activity curve to aid in the estimation of cer tain parameters in the general model shown in Fig. 1.…”

Effects of Moderate Hypoxemia and Unilateral Carotid Ligation on Cerebral Glucose Metabolism and Acid-Base Balance in the Rat

“…Salford et al (1973b) re ported the normal brain glucose content to be 4.5 ± 0.2 mmollkg wet weight (±SEM), rising to 6.4 ± 0.4 mmollkg wet weight in the intact hemisphere and to 5.64 ± 0.3 mmollkg wet weight in the clamped hemisphere at a mean P a02 of 28 mm Hg. Further support for the normality of the LC is derived from a report by Gjedde et al (1985). They found two types of infarcts: one in which perfusion is limited and glucose transport and brain glucose content are low, resulting in LC values of > 1; and a second type characterized by a limitation of phosphoryla tion, with normal brain glucose content and LC val ues.…”