Glucose is the principal source of energy for the brain and yet the dynamic response of glucose utilization to changes in brain activity is still not fully understood. Positron emission tomography (PET) allows quantitative measurement of glucose metabolism using 2-[18F]-fluorodeoxyglucose (FDG). However, FDG PET in its current form provides an integral (or average) of glucose consumption over tens of minutes and lacks the temporal information to capture physiological alterations associated with changes in brain activity induced by tasks or drug challenges. Traditionally, changes in glucose utilization are inferred by comparing two separate scans, which significantly limits the utility of the method. We report a novel method to track changes in FDG metabolism dynamically, with higher temporal resolution than exists to date and within a single session. Using a constant infusion of FDG, we demonstrate that our technique (termed fPET-FDG) can be used in an analysis pipeline similar to fMRI to define within-session differential metabolic responses. We use visual stimulation to demonstrate the feasibility of this method. This new method has a great potential to be used in research protocols and clinical settings since fPET-FDG imaging can be performed with most PET scanners and data acquisition and analysis is straightforward. fPET-FDG is a highly complementary technique to MRI and provides a rich new way to observe functional changes in brain metabolism.

This study employed simultaneous neuroimaging with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) to demonstrate the relationship between changes in receptor occupancy measured by PET and changes in brain activity inferred by fMRI. By administering the D2/D3 dopamine receptor antagonist [ 11 C]raclopride at varying specific activities to anesthetized nonhuman primates, we mapped associations between changes in receptor occupancy and hemodynamics [cerebral blood volume (CBV)] in the domains of space, time, and dose. Mass doses of raclopride above tracer levels caused increases in CBV and reductions in binding potential that were localized to the dopamine-rich striatum. Moreover, similar temporal profiles were observed for specific binding estimates and changes in CBV. Injection of graded raclopride mass doses revealed a monotonic coupling between neurovascular responses and receptor occupancies. The distinct CBV magnitudes between putamen and caudate at matched occupancies approximately matched literature differences in basal dopamine levels, suggesting that the relative fMRI measurements reflect basal D2/D3 dopamine receptor occupancy. These results can provide a basis for models that relate dopaminergic occupancies to hemodynamic changes in the basal ganglia. Overall, these data demonstrate the utility of simultaneous PET/fMRI for investigations of neurovascular coupling that correlate neurochemistry with hemodynamic changes in vivo for any receptor system with an available PET tracer.he neural basis of functional magnetic resonance imaging (fMRI) signals has been a topic of extensive investigation. Experimental correlations of fMRI signals or cerebral blood flow with relative changes in glucose or oxygen utilization (1-3) have been performed to determine whether hemodynamic responses reflect a coupling with metabolism-a hypothesis with a long history (4). To relate hemodynamic responses more directly to neural circuitry, fMRI or optical imaging signals have been correlated with electrophysiology, using graded levels of stimulation in preclinical models (5-7). These results generally demonstrate a monotonic coupling between electrical activity and evoked cortical hemodynamic responses, using sensory stimuli. However, the methodology is not readily extensible to human subjects, and the implications of such studies are difficult to generalize to pharmacotherapies or other drug stimuli that target specific neurotransmitter systems.Recent technological advances in multimodal imaging have enabled the simultaneous acquisition of MRI and positron emission tomography (PET) data (8). One of the motivations for conjoining these modalities was the potential for new insights into neural function based upon the complementary natures of PET and fMRI. In activation paradigms, fMRI provides excellent spatio-temporal resolution for localizing changes in brain activity but offers little insight into the underlying neurotransmission. Conversely, although PET has more limited temporal and spati...