Quantitative positron emission tomography (PET) studies of neurodegenerative diseases typically require the measurement of arterial input functions (AIF), an invasive and risky procedure. This study aims to assess the reproducibility of [11C]DPA-713 PET kinetic analysis using population-based input function (PBIF). The final goal is to possibly eliminate the need for AIF. Eighteen subjects including six healthy volunteers (HV) and twelve Parkinson disease (PD) subjects from two [11C]-DPA-713 PET studies were included. Each subject underwent 90 min of dynamic PET imaging. Five healthy volunteers underwent a test-retest scan within the same day to assess the repeatability of the kinetic parameters. Kinetic modeling was carried out using the Logan total volume of distribution (VT) model. For each data set, kinetic analysis was performed using a patient-specific AIF (PSAIF, ground-truth standard) and then repeated using the PBIF. PBIF was generated using the leave-one-out method for each subject from the remaining 17 subjects and after normalizing the PSAIFs by 3 techniques: (a) Weightsubject×DoseInjected, (b) area under AIF curve (AUC), and (c) Weightsubject×AUC. The variability in the VT measured with PSAIF, in the test-retest study, was determined for selected brain regions (white matter, cerebellum, thalamus, caudate, putamen, pallidum, brainstem, hippocampus, and amygdala) using the Bland-Altman analysis and for each of the 3 normalization techniques. Similarly, for all subjects, the variabilities due to the use of PBIF were assessed. Bland-Altman analysis showed systematic bias between test and retest studies. The corresponding mean bias and 95% limits of agreement (LOA) for the studied brain regions were 30% and ± 70%. Comparing PBIF- and PSAIF-based VT estimate for all subjects and all brain regions, a significant difference between the results generated by the three normalization techniques existed for all brain structures except for the brainstem (P-value = 0.095). The mean % difference and 95% LOA is −10% and ±45% for Weightsubject×DoseInjected; +8% and ±50% for AUC; and +2% and ± 38% for Weightsubject×AUC. In all cases, normalizing by Weightsubject×AUC yielded the smallest % bias and variability (% bias = ±2%; LOA = ±38% for all brain regions). Estimating the reproducibility of PBIF-kinetics to PSAIF based on disease groups (HV/PD) and genotype (MAB/HAB), the average VT values for all regions obtained from PBIF is insignificantly higher than PSAIF (%difference = 4.53%, P-value = 0.73 for HAB; and %difference = 0.73%, P-value = 0.96 for MAB). PBIF also tends to overestimate the difference between PD and HV for HAB (% difference = 32.33% versus 13.28%) and underestimate it in MAB (%difference = 6.84% versus 20.92%). PSAIF kinetic results are reproducible with PBIF, with variability in VT within that obtained for the test-retest studies. Therefore, VT assessed using PBIF-based kinetic modeling is clinically feasible and can be an alternative to PSAIF.

中文翻译：

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基于人群的输入函数，用于[ ¹¹ C] -DPA-713的TSPO定量和动力学建模

对神经退行性疾病的定量正电子发射断层扫描（PET）研究通常需要测量动脉输入功能（AIF），这是一种侵入性和高风险的程序。这项研究旨在评估基于人群的输入函数（PBIF）的[11C] DPA-713 PET动力学分析的可重复性。最终目标是可能消除对AIF的需求。来自两项[11C] -DPA-713 PET研究的18名受试者包括6名健康志愿者（HV）和12名帕金森氏病（PD）。每个受试者进行90分钟的动态PET成像。五名健康​​志愿者在同一天进行了一次重新测试扫描，以评估动力学参数的可重复性。使用Logan总分布体积（VT）模型进行动力学建模。对于每个数据集，使用患者特定的AIF（PSAIF，地面真实标准）进行动力学分析，然后使用PBIF进行重复分析。PBIF是使用剩下的17名受试者的留一法从每个受试者中生成的，并通过3种技术将PSAIF标准化后：（a）体重受试者×注射剂量，（b）AIF曲线下的面积（AUC），和（c）体重受试者×AUC。在再测试研究中，使用Bland-Altman分析法确定了选定的大脑区域（白质，小脑，丘脑，尾状，壳状核，苍白球，脑干，海马和杏仁核）中用PSAIF测量的VT的变异性。 3种归一化技术中的每一种。类似地，对于所有受试者，评估了由于使用PBIF而引起的变异性。布兰德·奥尔特曼（Bland-Altman）分析显示，测试研究与重新测试研究之间存在系统偏差。对于研究的大脑区域，相应的平均偏倚和95％的同意限（LOA）为30％和±70％。比较所有受试者和所有大脑区域的基于PBIF和PSAIF的VT估计值，除脑干（P值= 0.095）之外，所有三种大脑结构都存在三种归一化技术产生的结果之间的显着差异。对于Weightsubject×DoseInjected，平均差异百分比和95％LOA为-10％和±45％；AUC分别为8％和±50％；而Weightsubject×AUC则为+ 2％和±38％。在所有情况下，通过Weightsubject×AUC进行归一化可产生最小的偏差和变异性百分比（偏差百分比=±2％；所有大脑区域的LOA =±38％）。根据疾病组（HV / PD）和基因型（MAB / HAB）估算PBIF动力学对PSAIF的可再现性，从PBIF获得的所有区域的平均VT值均显着高于PSAIF（HAB的％差异= 4.53％，P值= 0.73； MAB的％差异= 0.73％，P值= 0.96）。PBIF还倾向于高估HAB的PD和HV之间的差异（％差异= 32.33％对13.28％），而在MAB中则低估了它（％差异= 6.84％对20.92％）。PSAIF动力学结果可以用PBIF再现，而VT的变化在重新测试研究中得到的范围内。因此，使用基于PBIF的动力学模型评估的VT在临床上是可行的，并且可以替代PSAIF。84％和20.92％）。PSAIF动力学结果可以用PBIF再现，而VT的变化在重新测试研究中得到的范围内。因此，使用基于PBIF的动力学模型评估的VT在临床上是可行的，并且可以替代PSAIF。84％和20.92％）。PSAIF动力学结果可以用PBIF再现，而VT的变化在重新测试研究中得到的范围内。因此，使用基于PBIF的动力学模型评估的VT在临床上是可行的，并且可以替代PSAIF。