Yu Amy S, Lin Hong-Dun, Huang Sung-Cheng, Phelps Michael E, Wu Hsiao-Ming
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California 90095-6948, USA.
J Nucl Med. 2009 Jun;50(6):966-73. doi: 10.2967/jnumed.108.060533. Epub 2009 May 14.
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 (18)F-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.
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 (18)F-FDG model (from which the (18)F-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.
The values of K(1), k(2), k(3), k(4), and K(FDG) 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 micromol/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) was observed. The standard cMR(glc) was also found to have strong correlations (r > 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)).
The (18)F-FDG rate constants of normal mouse cerebral cortex were determined. These values can be used in the k(4)-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.
本研究的目的是使用小动物正电子发射断层扫描（PET）以及通过微流控血液采样器获得的可靠血液曲线，评估多种估算小鼠脑内葡萄糖代谢率（cMR(glc)）的方法。估算了正常小鼠大脑皮质的（18）F - 氟代脱氧葡萄糖（FDG）速率常数的典型值，并将其用于cMR(glc)的计算。还评估了在各种定量方法中使用图像衍生的肝脏时间 - 活性曲线作为替代输入函数的可行性。
对13只血糖正常的C57BL / 6小鼠进行研究。通过微流控血液采样器从股动脉采集18份血样。从PET图像中得出组织时间 - 活性曲线。在各种定量方法中，使用2种不同的输入函数（一种来自血样[IF(血液)]，另一种来自肝脏时间 - 活性曲线[IF(肝脏)]）计算cMR(glc)值，这些方法包括三室（18）F - FDG模型（从中得出（18）F - FDG速率常数）、Patlak分析和运算方程。基于IF(血液)和三室模型估算的cMR(glc)值用作与其他方法计算的cMR(glc)值进行比较的标准。
通过IF(血液)和三室模型估算的K(1)、k(2)、k(3)、k(4)和K(FDG)值分别为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和0.024±0.007 mL/min/g。因此，标准cMR(glc)值为40.6±13.3 μmol/100 g/min（集总常数 = 0.6）。未观察到标准cMR(glc)与包含k(4)的运算方程估算的cMR(glc)之间存在显著差异。还发现标准cMR(glc)与三室模型中使用IF(肝脏)估算的cMR(glc)值以及与Patlak分析（使用IF(血液)或IF(肝脏)）估算的cMR(glc)值具有强相关性（r > 0.8）。
确定了正常小鼠大脑皮质的（18）F - FDG速率常数。这些值可用于包含k(4)的运算方程中以计算cMR(glc)。在本研究包含的大多数方法中，通过适当的线性校正，IF(肝脏)可用于估算cMR(glc)。还证实了在小鼠PET研究中使用Patlak分析估算cMR(glc)的有效性。
