Estimation from PET data of transient changes in dopamine concentration induced by alcohol: support for a non-parametric signal estimation method
Estimation from PET data of transient changes in dopamine concentration induced by alcohol: support for a non-parametric signal estimation method
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DOI：
10.1088/0031-9155/53/5/012
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发表时间：
2008-03-07
影响因子：
3.5
通讯作者：
Morris, E. D.
中科院分区：
文献类型：
--
作者：
Constantinescu, C. C.;Yoder, K. K.;Morris, E. D.
我们以前开发了一种模型独立的技术（非参数ntPET），用于从受体配体的配对（静息和激活）PET研究中提取神经递质浓度的瞬时变化。为了支持我们的方法，我们介绍了基于Endres和卡森（1998 J. Cereb.血流代谢18 1196-210）和Yoder等人（2004 J.Nucl.Med.45 903-11），并在实验数据上测试了它们。所有三个假设都描述了估计的游离（突触）多巴胺曲线（F（DA）（t））和结合电位变化（Δ BP）之间的关系。当数据符合以下假设行为时，支持非参数ntPET恢复的FDA（t）曲线的准确性：（1）Δ BP应随DA达峰时间的增加而下降，（2）Δ BP应随FDA（t）和游离雷氯必利（F（RAC）（t））曲线之间的时间相关性强度的增加而增加，（3）Δ BP应随受体位点的有效加权可用性线性下降。我们分析了8名健康受试者的局部脑数据，他们接受了两次[（11）C]雷氯必利扫描：一次是在休息时，另一次是在非预期的静脉注射酒精刺激多巴胺释放期间。对于几个纹状体区域，应用非参数ntPET来恢复FDA（t），并确定结合电位值。Kendall秩相关分析证实，FDA（t）数据符合所有三个验证假设的预期趋势。我们的研究结果使我们的FDA（t）的模型独立估计可信。非参数ntPET的应用可能会产生重要的见解如何改变多巴胺能神经传递的时间参与成瘾和其他精神疾病的病理。
We previously developed a model-independent technique (non-parametric ntPET) for extracting the transient changes in neurotransmitter concentration from paired (rest & activation) PET studies with a receptor ligand. To provide support for our method, we introduced three hypotheses of validation based on work by Endres and Carson (1998 J. Cereb. Blood Flow Metab. 18 1196-210) andYoder et al (2004 J. Nucl. Med. 45 903-11), and tested them on experimental data. All three hypotheses describe relationships between the estimated free (synaptic) dopamine curves (F(DA)(t)) and the change in binding potential (Delta BP). The veracity of the FDA(t) curves recovered by nonparametric ntPET is supported when the data adhere to the following hypothesized behaviors: (1) Delta BP should decline with increasing DA peak time, (2) Delta BP should increase as the strength of the temporal correlation between FDA( t) and the free raclopride (F(RAC)(t)) curve increases, (3) Delta BP should decline linearly with the effective weighted availability of the receptor sites. We analyzed regional brain data from 8 healthy subjects who received two [(11)C] raclopride scans: one at rest, and one during which unanticipated IV alcohol was administered to stimulate dopamine release. For several striatal regions, nonparametric ntPET was applied to recover FDA( t), and binding potential values were determined. Kendall rank-correlation analysis confirmed that the FDA( t) data followed the expected trends for all three validation hypotheses. Our findings lend credence to our model- independent estimates of FDA(t). Application of nonparametric ntPET may yield important insights into how alterations in timing of dopaminergic neurotransmission are involved in the pathologies of addiction and other psychiatric disorders.