Regional Kinetic Constants and Cerebral Metabolic Rate for Glucose in Normal Human Volunteers Determined by Dynamic Positron Emission Tomography of [18F]-2-Fluoro-2-Deoxy-D-Glucose

Abstract

Using dynamic [¹⁸F]fluorodeoxyglucose (FDG) positron emission tomography with a high-resolution, seven-slice positron camera, the kinetic constants of the original three-compartment model of Sokoloff and co-workers (1977) were determined in 43 distinct topographic brain regions of seven healthy male volunteers aged 28–38 years. Regional averages of the cerebral metabolic rate for glucose (CMR_glu) were calculated both from individually fitted rate constants (CMR_glukinetic) and from activity maps recorded 30–40 min after FDG injection, employing a four-parameter operational equation with standard rate constants from the literature (CMR_gluautoradiographic). Metabolic rates and kinetic constants varied significantly among regions and subjects, but not between hemispheres. k₁ ranged between 0.0485 ± 0.00778 min⁻¹ in the oval center and 0.0990 ± 0.01347 min⁻¹ in the primary visual cortex. k₂ ranged from 0.1198 ± 0.01533 min⁻¹ in the temporal white matter to 0.1472 ± 0.01817 min⁻¹ in the cerebellar dentate nucleus. k₃ was lowest (0.0386 ± 0.01482 min⁻¹) in temporal white matter and highest (0.0823 ± 0.02552 min⁻¹) in the caudate nucleus. Maximum likelihood cluster analysis revealed four homogeneous groups of brain regions according to their respective kinetic constants: (1) white matter and mixed brainstem structures; (2) cerebellar gray matter and hippocampal formations; (3) basal ganglia and frontolateral and primary visual cortex; and (4) other cerebral cortex and thalamus. Across the entire brain, k₁ and k₂ were positively correlated (r = 0.79); k₁ and k₃ showed some correlation (r = 0.59); but no significant linear association was found between k₂ and k₃. A strong correlation with CMR_glu could be demonstrated for k₁ (r = 0.88) and k₃ (r = 0.90), but k₂ was loosely correlated (r = 0.56). CMR_glu kinetic ranged from 17.0 ± 2.45 μmol/100 g/min in the occipital white matter to 41.1 ± 5.62 μmol/100 g/min in the frontolateral cortex. In most regions the mean values of CMR_glu kinetic did not differ significantly from CMR_glu autoradiographic. With few exceptions, however, within-region variance was significantly less for CMR_glu kinetic than for CMR_glu autoradiographic, suggesting greater individual reliability of results obtained by the kinetic approach.