Quantification of Task-Specific Glucose Metabolism with Constant Infusion of 18F-FDG

The investigation of cerebral metabolic rate of glucose (CMRGlu) at baseline and during specific tasks previously required separate scans with the drawback of high intrasubject variability. We aimed to validate a novel approach to assessing baseline glucose metabolism and task-specific changes in a single measurement with a constant infusion of F-18-FDG. Methods: Fifteen healthy subjects underwent two PET measurements with arterial blood sampling. As a reference, baseline CMRGIu was quantified from a 60-min scan after F-18-FDG bolus application using the Patlak plot (eyes closed). For the other scan, a constant radioligand infusion was applied for 95 min, during which the subjects opened their eyes at 10-20 min and 60-70 min and tapped their right thumb to their fingers at 35-45 min and 85-95 min. The constant-infusion scan was quantified in two steps. First, the general linear model was used to fit regional time-activity curves with regressors for baseline metabolism, task-specific changes for the eyes-open and finger-tapping conditions, and movement parameters. Second, the Patlak plot was used for quantification of CMRGIu. Multiplication of the baseline regressor by beta-values from the general linear model yielded regionally specific time-activity curves for baseline metabolism. Further, task specific changes in metabolism are directly proportional to changes in the slope of the time-activity curve and hence to changes in CMRGIu. Results: Baseline CMRGIu from the constant-infusion scan matched that from the bolus application (test-retest variability, 1.1% +/- 24.7%), which was not the case for a previously suggested approach (variability, -39.9% +/- 25.2%, P < 0.001). Task-specific CMRGIu increased in the primary visual and motor cortices for eyes open and finger tapping, respectively (P < 0.05, familywise error corrected), with absolute changes of up to 2.1 mu mol/100 g/min and 6.3% relative to baseline. For eyes open, a decreased CMRGIu was observed in default-mode regions (P < 0.05, familywise error corrected). CMRGIu quantified with venous blood samples (n = 6) showed excellent agreement with results obtained from arterial samples (r > 0.99). Conclusion: Baseline glucose metabolism and task specific changes can be quantified in a single measurement with constant infusion of F-18-FDG and venous blood sampling. The high sensitivity and regional specificity of the approach offer novel possibilities for functional and multimodal brain imaging.