Quantification of Cerebral Glucose Metabolic Rate in Mice Using 18F-FDG and Small-Animal PET

摘要

The aim of this study was to evaluate various methods for estimating the metabolic rate of glucose utilization in the mouse brain (cMRglc) using small-animal PET and reliable blood curves derived by a microfluidic blood sampler. Typical values of 18F-FDG rate constants of normal mouse cerebral cortex were estimated and used for cMRglc calculations. The feasibility of using the image-derived liver timea€“activity curve as a surrogate input function in various quantification methods was also evaluated. Methods: Thirteen normoglycemic C57BL/6 mice were studied. Eighteen blood samples were taken from the femoral artery by the microfluidic blood sampler. Tissue timea€“activity curves were derived from PET images. cMRglc values were calculated using 2 different input functions (one derived from the blood samples [IFblood] and the other from the liver timea€“activity curve [IFliver]) in various quantification methods, which included the 3-compartment 18F-FDG model (from which the 18F-FDG rate constants were derived), the Patlak analysis, and operational equations. The estimated cMRglc value based on IFblood and the 3-compartment model served as a standard for comparisons with the cMRglc values calculated by the other methods. Results: The values of , , , , and estimated by IFblood and the 3-compartment model were 0.22 ?± 0.05 mL/min/g, 0.48 ?± 0.09 mina?’1, 0.06 ?± 0.02 mina?’1, 0.025 ?± 0.010 mina?’1, and 0.024 ?± 0.007 mL/min/g, respectively. The standard cMRglc value was, therefore, 40.6 ?± 13.3 ??mol/100 g/min (lumped constant = 0.6). No significant difference between the standard cMRglc and the cMRglc estimated by the operational equation that includes was observed. The standard cMRglc was also found to have strong correlations (r 0.8) with the cMRglc value estimated by the use of IFliver in the 3-compartment model and with those estimated by the Patlak analysis (using either IFblood or IFliver). Conclusion: The 18F-FDG rate constants of normal mouse cerebral cortex were determined. These values can be used in the -included operational equation to calculate cMRglc. IFliver can be used to estimate cMRglc in most methods included in this study, with proper linear corrections applied. The validity of using the Patlak analysis for estimating cMRglc in mouse PET studies was also confirmed.