Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW, Australia; Brain & Mind Research Institute, University of Sydney, Sydney, NSW, Australia.
Brain & Mind Research Institute, University of Sydney, Sydney, NSW, Australia.
Neuroimage. 2014 Aug 15;97:29-40. doi: 10.1016/j.neuroimage.2014.04.010. Epub 2014 Apr 14.
Positron emission tomography (PET) with [(11)C]Raclopride is an important tool for studying dopamine D2 receptor expression in vivo. [(11)C]Raclopride PET binding experiments conducted using the Partial Saturation Approach (PSA) allow the estimation of receptor density (B(avail)) and the in vivo affinity appK(D). The PSA is a simple, single injection, single scan experimental protocol that does not require blood sampling, making it ideal for use in longitudinal studies. In this work, we generated a complete Monte Carlo simulated PET study involving two groups of scans, in between which a biological phenomenon was inferred (a 30% decrease of B(avail)), and used it in order to design an optimal data processing chain for the parameter estimation from PSA data. The impact of spatial smoothing, noise removal and image resolution recovery technique on the statistical detection was investigated in depth. We found that image resolution recovery using iterative deconvolution of the image with the system point spread function associated with temporal data denoising greatly improves the accuracy and the statistical reliability of detecting the imposed phenomenon. Before optimisation, the inferred B(avail) variation between the two groups was underestimated by 42% and detected in 66% of cases, while a false decrease of appK(D) by 13% was detected in more than 11% of cases. After optimisation, the calculated B(avail) variation was underestimated by only 3.7% and detected in 89% of cases, while a false slight increase of appK(D) by 3.7% was detected in only 2% of cases. We found during this investigation that it was essential to adjust a factor that accounts for difference in magnitude between the non-displaceable ligand concentrations measured in the target and in the reference regions, for different data processing pathways as this ratio was affected by different image resolutions.
正电子发射断层扫描(PET)与[(11)C]Raclopride 是研究体内多巴胺 D2 受体表达的重要工具。使用部分饱和方法(PSA)进行的[(11)C]Raclopride PET 结合实验允许估计受体密度(B(可用))和体内亲和力 appK(D)。PSA 是一种简单的、单次注射、单次扫描的实验方案,不需要采血,非常适合用于纵向研究。在这项工作中,我们生成了一个完整的蒙特卡罗模拟 PET 研究,涉及两组扫描,在这两组扫描之间推断出一个生物学现象(B(可用)减少 30%),并使用它来设计从 PSA 数据估计参数的最佳数据处理链。我们深入研究了空间平滑、噪声消除和图像分辨率恢复技术对统计检测的影响。我们发现,使用与时间数据去噪相关联的系统点扩散函数对图像进行迭代反卷积的图像分辨率恢复极大地提高了检测所施加现象的准确性和统计可靠性。在优化之前,两组之间推断出的 B(可用)变化被低估了 42%,并且在 66%的情况下检测到,而超过 11%的情况下检测到 appK(D)的虚假轻微下降 13%。在优化之后,计算出的 B(可用)变化仅被低估了 3.7%,并且在 89%的情况下检测到,而只有 2%的情况下检测到 appK(D)的虚假轻微增加 3.7%。在这项研究中,我们发现必须根据不同的数据处理途径调整一个因子,该因子考虑了目标和参考区域中测量的非置换配体浓度之间的幅度差异,因为该比率受到不同图像分辨率的影响。