Center for Radiopharmaceutical Sciences of ETH, PSI, and USZ, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich CH-8093, Switzerland.
Collegium Helveticum ETH and UZH, Zurich 8092, Switzerland.
EJNMMI Res. 2013 Aug 6;3:61. doi: 10.1186/2191-219X-3-61. eCollection 2013.
Kinetic modeling of brain glucose metabolism in small rodents from positron emission tomography (PET) data using 2-deoxy-2-[(18) F]fluoro-d-glucose (FDG) has been highly inconsistent, due to different modeling parameter settings and underestimation of the impact of methodological flaws in experimentation. This article aims to contribute toward improved experimental standards. As solutions for arterial input function (IF) acquisition of satisfactory quality are becoming available for small rodents, reliable two-tissue compartment modeling and the determination of transport and phosphorylation rate constants of FDG in rodent brain are within reach.
Data from mouse brain FDG PET with IFs determined with a coincidence counter on an arterio-venous shunt were analyzed with the two-tissue compartment model. We assessed the influence of several factors on the modeling results: the value for the fractional blood volume in tissue, precision of timing and calibration, smoothing of data, correction for blood cell uptake of FDG, and protocol for FDG administration. Kinetic modeling with experimental and simulated data was performed under systematic variation of these parameters.
Blood volume fitting was unreliable and affected the estimation of rate constants. Even small sample timing errors of a few seconds lead to significant deviations of the fit parameters. Data smoothing did not increase model fit precision. Accurate correction for the kinetics of blood cell uptake of FDG rather than constant scaling of the blood time-activity curve is mandatory for kinetic modeling. FDG infusion over 4 to 5 min instead of bolus injection revealed well-defined experimental input functions and allowed for longer blood sampling intervals at similar fit precisions in simulations.
FDG infusion over a few minutes instead of bolus injection allows for longer blood sampling intervals in kinetic modeling with the two-tissue compartment model at a similar precision of fit parameters. The fractional blood volume in the tissue of interest should be entered as a fixed value and kinetics of blood cell uptake of FDG should be included in the model. Data smoothing does not improve the results, and timing errors should be avoided by precise temporal matching of blood and tissue time-activity curves and by replacing manual with automated blood sampling.
由于建模参数设置不同以及对实验方法缺陷的影响估计不足，从小鼠正电子发射断层扫描（PET）数据中对脑葡萄糖代谢进行动力学建模一直存在很大差异。本文旨在提高实验标准。由于小型啮齿动物的动脉输入函数（IF）采集的解决方案变得可行，因此可靠的两组织室模型和确定 FDG 在啮齿动物脑中的转运和磷酸化速率常数成为可能。
使用吻合计数器在动静脉分流器上确定 IF 的小鼠脑 FDG PET 数据使用双组织室模型进行分析。我们评估了几个因素对建模结果的影响：组织中血液体积分数的值、计时和校准的精度、数据平滑、FDG 血细胞摄取的校正以及 FDG 给药方案。在这些参数的系统变化下，对实验和模拟数据进行了动力学建模。
血液体积拟合不可靠，影响了速率常数的估计。即使是几秒钟的小样本计时误差也会导致拟合参数的显著偏差。数据平滑不会增加模型拟合精度。准确校正 FDG 血细胞摄取的动力学而不是对血液时间-活性曲线进行常数缩放对于动力学建模是强制性的。与推注注射相比，4 至 5 分钟的 FDG 输注可显示出明确的实验输入功能，并允许在相似的拟合精度下在模拟中进行更长的血液采样间隔。
与推注注射相比，几分钟的 FDG 输注允许在使用双组织室模型进行动力学建模时以相似的拟合参数精度进行更长的血液采样间隔。应将感兴趣组织中的血液体积分数作为固定值输入，并在模型中包括 FDG 血细胞摄取的动力学。数据平滑不会改善结果，应通过精确的血液和组织时间-活性曲线的时间匹配以及用自动血液采样代替手动血液采样来避免计时误差。
