With the advent and emerging importance of neurobiology and its relation to behavior, scientists desire the capability to apply noninvasive, quantitative imaging of neuronal activity to small rodents. To this end, the authors' laboratory has developed microPET, a high-resolution positron emission tomography (PET) scanner that is capable of performing in vivo molecular imaging at a resolution sufficient to resolve major structures in the rat brain. The authors report in this article that, in conjunction with 2-[18F]fluoro-2-deoxyglucose (FDG), microPET provides accurate rates of cerebral glucose metabolism (59.7 to 108.5 micromol/100 g x min) in conscious adult rats as validated by within-subject autoradiographic measurements (59.5 to 136.2 micromol/100 g x min; r = 0.88; F[1,46] = 168.0; P < 0.001). By conducting repeated quantitative scanning, the authors demonstrate the sensitivity and accuracy of FDG-microPET to detect within-subject metabolic changes induced by traumatic brain injury. In addition, the authors report that longitudinal recovery from traumatic brain injury-induced metabolic depression, as measured by quantitative FDG-microPET, is significantly correlated (r = 0.65; P < 0.05) to recovery of behavioral dysfunction, as assessed by the Morris Water Maze performance of the same rats, after injury. This is the first study to demonstrate that FDG-microPET is quantitative, reproducible, and sensitive to metabolic changes, introducing a new approach to the longitudinal study of small animal models in neuroscience research.