In vivo quantification of serotonin transporters using [11C]DASB and positron emission tomography in humans:: modeling considerations
In vivo quantification of serotonin transporters using [11C]DASB and positron emission tomography in humans:: modeling considerations
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DOI：
10.1038/sj.jcbfm.9600329
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发表时间：
2007-01-01
影响因子：
6.3
通讯作者：
Parsey, Ramin V.
中科院分区：
文献类型：
--
作者：
Ogden, R. Todd;Ojha, Ashish;Parsey, Ramin V.
人脑中5-羟色胺转运体（5-HTT）的正电子发射断层扫描（PET）研究越来越多地使用放射性配体[C-11] N， N-二甲基-2-（2-氨基-4-氰苯基硫）苄基胺。在一些已发表的文章中，各种模型已应用于此类数据；然而，到目前为止，这些模型还没有得到测试-重测试数据的验证。我们招募了11名健康受试者，并在同一天对每个受试者进行了两次相同的扫描。我们考虑了四种不同的模型（一种和两种组织隔室动力学模型，图形分析中的似然估计（LEGA；图形方法的无偏差替代方案）和基追寻）以及对动力学模型的快速非迭代近似。我们考虑了四种不同的结果测量指标（分布总量（VT）、有（BP）和没有（BP1）的结合电位、自由分数调整和特异性-非特异性平衡分配系数（BP2））。为了评估每个模型的性能，我们使用六种不同的指标（百分比差（PD）和受试者内平均平方和的再现性，类间系数的可靠性，受试者间方差，基于每种方法残差的自提重采样的可识别性，以及时间稳定性分析以确定所需的最小扫描时间）比较了结果。我们考虑了体素水平和感兴趣区域（ROI）水平的分析，并比较了这两种方法的结果来评估一致性。我们确定，100分钟的扫描时间是足够的，并为投资回报率水平的分析，LEGA给出了最好的结果。所有地区VT的平均PD为5.51，BP为20.7，BP1为17.2，BP2为16.5。对于体素级分析，我们确定单组织室非迭代模型是最好的。
Positron emission tomography ( PET) studies of the serotonin transporter (5-HTT) in the human brain are increasingly using the radioligand [C-11] N, N-dimethyl-2-(2-amino-4-cyanophenylthio) benzylamine. A variety of models have been applied to such data in several published articles; however to date, these models have not been validated with test-retest data. We recruited 11 healthy subjects and conducted two identical scans on each subject on the same day. We considered four different models (one-and two-tissue compartment kinetic models, likelihood estimation in graphical analysis (LEGA; a bias-free alternative to the graphical method), and basis pursuit) along with fast noniterative approximations to the kinetic models. We considered four different outcome measures (total volume of distribution (VT), binding potential with (BP) and without (BP1), free-fraction adjustment, and specific-to-nonspecific equilibrium partition coefficient (BP2)). To assess the performance of each model, we compared results using six different metrics ( percent difference (PD) and within-subject mean sum of squares for reproducibility, interclass coefficient for reliability, variance across subjects, identifiability based on bootstrap resampling of residuals for each method, and time stability analysis to determine minimal required scanning time). We considered analysis of both at the voxel level and at the region of interest (ROI) level and compared results from these two approaches to assess agreement. We determined that 100 mins of scanning time is adequate and that for ROI- level analysis, LEGA gives best results. Average PD is 5.51 for VT, 20.7 for BP, 17.2 for BP1, and 16.5 for BP2 across all regions. For voxel-level analysis we determined that the one-tissue compartment noniterative model is best.