Max Planck Institute for Neurological Research, Cologne, Germany.
J Nucl Med. 2011 Aug;52(8):1252-60. doi: 10.2967/jnumed.110.085266. Epub 2011 Jul 15.
Diseases and dysfunction of the central nervous system are often associated with regional changes in cerebral glucose metabolism, which can be measured in vivo by PET using (18)F-FDG as the tracer. For quantification, the arterial tracer input function must be determined. For rodents in particular, direct measurement of blood radioactivity concentration is scarcely feasible for follow-up of individual animals because of the invasiveness of blood sampling. We show that the whiskers area of the rat's muzzle serves as an extracerebral reference region. The derived model also takes into account local variations of the lumped constant, which is crucial in pathologic tissue.
In 11 rats, the reference tissue kinetic parameters were determined from PET data and measured whole blood radioactivity concentration. Parametric images of cerebral kinetic rate constants were calculated using the directly measured input function, the reference tissue time-activity curve with individually fitted reference kinetic parameters, and the reference time-activity curve with fixed reference kinetic parameters calculated from the fitted parameters averaged over all animals. The need for kinetic modeling in disease models is demonstrated in 5 rats subjected to acute focal cerebral ischemia. (18)F-FDG metabolism and transport rate constants and local cerebral glucose metabolic rates were calculated.
Cerebral kinetic constants derived from the 3 methods corresponded closely. The maximum difference in whole-brain kinetic parameters observed between the directly measured input function and the reference tissue time-activity curve with individually fitted reference kinetic parameters was less than 5%. Taking fixed reference parameters (the reference time-activity curve with fixed reference kinetic parameters calculated from the fitted parameters averaged over all animals) still provided whole-brain kinetic parameters with an accuracy of approximately 90%. In the rats subjected to focal cerebral ischemia, (18)F-FDG kinetic parameters in healthy tissue were not significantly different from whole-brain kinetic parameters in naive rats. The ischemic region was characterized by preserved glucose metabolism, although (18)F-FDG uptake was elevated significantly-that is, the lumped constant in the ischemic region was different from that of healthy brain tissue.
The method presented here allows for the quantitative noninvasive determination of cerebral glucose consumption in rats, takes into account local variations of the lumped constant, and is suitable for follow-up measurements of individuals.
中枢神经系统的疾病和功能障碍通常与脑葡萄糖代谢的区域性变化有关，这种变化可以通过 PET 利用（18）F-FDG 作为示踪剂在体内进行测量。为了定量，必须确定动脉示踪剂输入函数。特别是对于啮齿动物，由于采血的侵入性，直接测量血液放射性浓度几乎不可能对单个动物进行后续研究。我们表明，大鼠口鼻部的胡须区域可用作脑外参考区域。该模型还考虑了总体常数的局部变化，这在病变组织中是至关重要的。
在 11 只大鼠中，通过 PET 数据和测量全血放射性浓度来确定参考组织动力学参数。使用直接测量的输入函数、具有个体拟合参考动力学参数的参考组织时间-活性曲线以及具有从所有动物平均拟合参数计算的固定参考动力学参数的参考时间-活性曲线，计算脑动力学速率常数的参数图像。在 5 只急性局灶性脑缺血大鼠中证明了疾病模型中动力学建模的必要性。计算（18）F-FDG 代谢和转运速率常数和局部脑葡萄糖代谢率。
从 3 种方法得出的脑动力学常数非常接近。在直接测量的输入函数和具有个体拟合参考动力学参数的参考组织时间-活性曲线之间观察到的整个大脑动力学参数的最大差异小于 5%。采用固定的参考参数（从所有动物平均拟合参数计算的具有固定参考动力学参数的参考时间-活性曲线）仍然可以提供准确度约为 90%的整个大脑动力学参数。在局灶性脑缺血大鼠中，健康组织中的（18）F-FDG 动力学参数与未处理大鼠的全脑动力学参数无显著差异。尽管（18）F-FDG 摄取显著升高，但缺血区域的葡萄糖代谢仍然得到保留，即缺血区域的总体常数与健康脑组织不同。
本文提出的方法允许对大鼠脑葡萄糖消耗进行定量的非侵入性测定，考虑了总体常数的局部变化，并且适合个体的后续测量。
