Cerebral Metabolic Variability As Studied By Sequential Injection Of Differentially-labeled Deoxyglucoses.

Abstract

Variability in the rate of cerebral glucose metabolism has been analyzed both between- and within-subjects, by means of novel sequential double-label autoradiographic approaches to the 2-deoxyglucose (2DG) method. Both an $\sp{18}$F/$\sp{14}$C- and a $\sp3$H/$\sp{14}$C-2DG sequential double-label technique presented here represent practicable quantitative methods which will permit the use of a test-retest experimental design at the autoradiographic level of resolution. There is considerable metabolic variability in measurements of the resting state, attributable both to differences between individual experimental subjects, as well as to within-subject factors. The observation that a component of the observed metabolic variability is global in nature suggests that the application of z-transformation analysis can reduce error in both conventional (single-label) as well as sequential double-label 2DG experiments. This latter experimental design thus retains the option of quantifying both regional pattern changes and global metabolic responses to experimental manipulations. The pattern alterations are manifested in the z-transformed data, while global alterations can be detected by statistical analysis of the means used for the transformations. By the use of methods developed in the present thesis, the statistical power of the 2DG method is enhanced, and the number of experimental animals needed to demonstrate a given effect on regional glucose utilization reduced. The present work is to our knowledge the first study of cerebral metabolic variability at the autoradiographic level of resolution.