Centre for Functionally Integrative Neuroscience, Aarhus University, Denmark.
Neuroimage. 2010 Feb 15;49(4):2933-9. doi: 10.1016/j.neuroimage.2009.11.035. Epub 2009 Nov 24.
PET studies with the DOPA decarboxylase substrate 6-[(18)F]fluoro-l-DOPA (FDOPA) reveal the storage of [(18)F]-fluorodopamine within synaptic vesicles, mainly of dopamine fibres. As such, FDOPA PET is a sensitive indicator of the integrity of the nigrostriatal dopamine innervation. Nonetheless, there have been several reports of focal elevations of FDOPA utilization in brain of patients with Parkinson's disease (PD), all based on reference tissue methods. To investigate this phenomenon further, we used voxel-wise steady-state kinetic analysis to search for regions of elevated FDOPA utilization (K; ml g(-1) min(-1)) and steady-state trapping (V(d); ml g(-1)) in a group of well-characterized patients with early, asymmetric PD, who were contrasted with an age-matched control group. Subtraction of the population mean parametric maps revealed foci of increased FDOPA utilization K (+25%) in the bilateral medial nucleus accumbens, whereas the expected declines in the trapping of FDOPA were seen in the caudate and putamen. This observation suggests hyperfunction of catecholamine fibres innervating specifically the limbic striatum, which could guide the design of future prospective FDOPA-PET studies of the impulse control disorders occurring in some PD patients under treatment with dopamine agonists. A focus of increased FDOPA influx and also V(d) was detected in the periaqueductal grey, consistent with some earlier reports based on reference tissue analysis. Increased FDOPA trapping in the periaqueductal grey of PD patients seems consistent with recent reports of increased activity of serotonin neurons in a rat model of parkinsonism.
正电子发射断层扫描(PET)研究使用 DOPA 脱羧酶底物 6-[(18)F]氟-L-多巴(FDOPA),可以揭示突触小泡内 [(18)F]-氟多巴胺的储存,主要是多巴胺纤维。因此,FDOPA PET 是黑质纹状体多巴胺神经支配完整性的敏感指标。尽管如此,已有几项关于帕金森病(PD)患者脑内 FDOPA 利用的局灶性升高的报告,所有这些报告均基于参考组织方法。为了进一步研究这一现象,我们使用体素稳态动力学分析,在一组特征明确的早期、不对称性 PD 患者中寻找 FDOPA 利用(K;ml g(-1) min(-1))和稳态捕获(V(d);ml g(-1))升高的区域,并将其与年龄匹配的对照组进行对比。人群均值参数图的减影显示,双侧伏隔核中 FDOPA 利用 K(增加 25%)增加的焦点,而在尾状核和壳核中则出现预期的 FDOPA 捕获下降。这一观察结果表明,特定地支配边缘纹状体的儿茶酚胺纤维的功能亢进,这可能指导未来使用多巴胺激动剂治疗的一些 PD 患者发生冲动控制障碍的前瞻性 FDOPA-PET 研究的设计。在导水管周围灰质中检测到 FDOPA 流入和 V(d)的增加焦点,与基于参考组织分析的一些早期报告一致。PD 患者导水管周围灰质中 FDOPA 捕获的增加似乎与帕金森病大鼠模型中 5-羟色胺神经元活性增加的最近报道一致。