Construction of Normal Database of Neurotransmission System in the Human Brain using Positron emission tomography

中枢多巴胺能系统在神经精神疾病的病理生理学中具有重要意义。PET可以估计突触前和突触后的多巴胺能功能。然而，包括受体、转运体和内源性神经递质合成在内的突触前和突触后多巴胺能功能的综合数据库尚未报道。在本研究中，我们利用PET建立了活体大脑突触前和突触后多巴胺能功能的正常数据库。对37例健康男性静脉注射c -11-雷氯pride、C-11-FLB457、C-11-PE2I或C-11-DOPA后，进行纹状体和纹状体外多巴胺d2受体结合、多巴胺转运体结合和内源性多巴胺合成的PET扫描。结合电位采用参考组织模型法逐体素计算。在C-11-DOPA的研究中，多巴胺的合成指数是由大脑的时间-活动曲线下的面积与参考区域的比值来计算的。使用SPM2对所有PET图像进行解剖标准化，并为每种放射性示踪剂建立数据库。这些数据库可以比较纹状体和纹状体外多巴胺d2受体结合、多巴胺转运体结合和内源性多巴胺合成的区域分布。纹状体与多巴胺d2受体和转运体结合最多，多巴胺合成最多。对于边缘系统，在杏仁核和前扣带观察到相对较高的多巴胺D2受体结合和相对较高的多巴胺合成。在新皮质区域中，颞叶皮层与多巴胺a受体的结合最高。新皮质区与多巴胺转运体的结合非常低。这些分布与人类死后研究的结果很好地吻合。该数据库有助于了解人脑中多巴胺能神经传递的生理机制，并可用于研究神经精神疾病中多巴胺能功能的区域异常。少

The central dopaminergic system is of interest in the pathophysiology of neuropsychiatric diseases. Both pre and postsynaptic dopaminergic functions can be estimated by PET. However, the integrated database of both pre and postsynaptic dopaminergic functions including receptors, transporter, and endogenous neurotransmitter synthesis has not been reported. In the present study, we have built the normal database of pre and postsynaptic dopaminergic functions in the living human brain using PET. Tb measure the striatal and extrastriatal dopamine D_2 receptor binding, dopamine transporter binding, and endogenous dopamine synthesis, PET scans were performed on total of 37 healthy men after intravenous injection of C-11-raclopride, C-11-FLB457, C-11-PE2I, or C-11-DOPA. The binding potential was calculated by the reference tissue model method on a voxel by voxel basis. For C-11-DOPA study, the dopamine synthesis index was calculated from the ratio of area under the time-activity curve of brai … More n regions to a reference region. All PET images were anatomically standardized using SPM2, and database was built for each radiotracer. These databases allow to compare regional distributions of the striatal and extrastriatal dopamine D_2 receptor binding, dopamine transporter binding, and endogenous dopamine synthesis. In the striatum, greatest bindings to dopamine D_2 receptors and transporters and greatest dopamine synthesis were observed. For the limbic system, relatively high bindings of dopamine D2 receptors and relatively high dopamine synthesis were observed in the amygdala and anterior cingulate. Among the neocortical regions, highest binding to dopamine a receptors was observed in the temporal cortex. The binding to dopamine transporter was very low in the neocortical regions. These distributions were in good agreement with those in the human post mortem studies. This database is useful to understand physiology of dopaminergic neurotransmission in the living human brain, and can be applied to investigate regional abnormality of dopaminergic functions in neuropsychiatric diseases. Less