Florence Nightingale's fever.

Abstract

The aim of this study was to evaluate various methods for estimating the metabolic rate of glucose utilization in the mouse brain (cMR_glc) 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 cMR_glc calculations. The feasibility of using the image-derived liver time–activity curve as a surrogate input function in various quantification methods was also evaluated. <b>Methods:</b> Thirteen normoglycemic C57BL/6 mice were studied. Eighteen blood samples were taken from the femoral artery by the microfluidic blood sampler. Tissue time–activity curves were derived from PET images. cMR_glc values were calculated using 2 different input functions (one derived from the blood samples [IF_blood] and the other from the liver time–activity curve [IF_liver]) 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 cMR_glc value based on IF_blood and the 3-compartment model served as a standard for comparisons with the cMR_glc values calculated by the other methods. <b>Results:</b> The values of \(\mathrm{K}_{1}^{{\ast}}\) , \(k_{2}^{{\ast}}\) , \(k_{3}^{{\ast}}\) , \(k_{4}^{{\ast}}\) , and \(\mathrm{K}_{\mathrm{FDG}}^{{\ast}}\) estimated by IF_blood and the 3-compartment model were 0.22 ± 0.05 mL/min/g, 0.48 ± 0.09 min⁻¹, 0.06 ± 0.02 min⁻¹, 0.025 ± 0.010 min⁻¹, and 0.024 ± 0.007 mL/min/g, respectively. The standard cMR_glc value was, therefore, 40.6 ± 13.3 μmol/100 g/min (lumped constant = 0.6). No significant difference between the standard cMR_glc and the cMR_glc estimated by the operational equation that includes \(k_{4}^{{\ast}}\) was observed. The standard cMR_glc was also found to have strong correlations (<i>r</i> &gt; 0.8) with the cMR_glc value estimated by the use of IF_liver in the 3-compartment model and with those estimated by the Patlak analysis (using either IF_blood or IF_liver). <b>Conclusion:</b> The ¹⁸F-FDG rate constants of normal mouse cerebral cortex were determined. These values can be used in the \(k_{4}^{{\ast}}\) -included operational equation to calculate cMR_glc. IF_liver can be used to estimate cMR_glc in most methods included in this study, with proper linear corrections applied. The validity of using the Patlak analysis for estimating cMR_glc in mouse PET studies was also confirmed.