Neurovascular coupling to D2/D3 dopamine receptor occupancy using simultaneous PET/functional MRI
Neurovascular coupling to D2/D3 dopamine receptor occupancy using simultaneous PET/functional MRI
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DOI：
10.1073/pnas.1220512110
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发表时间：
2013-07-02
影响因子：
11.1
通讯作者：
Mandeville, Joseph B.
中科院分区：
文献类型：
--
作者：
Sander, Christin Y.;Hooker, Jacob M.;Mandeville, Joseph B.
本研究采用正电子发射断层扫描（PET）和功能磁共振成像（fMRI）同时进行神经成像，以证明PET测量的受体占用变化与fMRI推断的脑活动变化之间的关系。通过给麻醉的非人灵长类动物注射D2/D3多巴胺受体拮抗剂[C-11]雷氯pride，我们在空间、时间和剂量范围内绘制了受体占用与血流动力学[脑血容量（CBV）]变化之间的关系。大剂量高于示踪剂水平的雷氯pride引起CBV的增加和结合电位的降低，这种结合电位定位于富含多巴胺的纹状体。此外，对于特定的结合估计和CBV的变化，观察到类似的时间分布。注射分级的雷氯pride质量剂量显示神经血管反应和受体占用之间的单调耦合。壳核和尾状核在匹配占用时的不同CBV值与文献中基础多巴胺水平的差异大致相符，表明相对的fMRI测量反映了基础D2/D3多巴胺受体占用。这些结果可以为建立多巴胺能占用与基底神经节血流动力学变化相关的模型提供基础。总的来说，这些数据证明了PET/fMRI同时用于研究神经血管耦合的实用性，这种耦合将神经化学与体内任何具有可用PET示踪剂的受体系统的血流动力学变化联系起来。
This study employed simultaneous neuroimaging with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) to demonstrate the relationship between changes in receptor occupancy measured by PET and changes in brain activity inferred by fMRI. By administering the D2/D3 dopamine receptor antagonist [C-11] raclopride at varying specific activities to anesthetized nonhuman primates, we mapped associations between changes in receptor occupancy and hemodynamics [cerebral blood volume (CBV)] in the domains of space, time, and dose. Mass doses of raclopride above tracer levels caused increases in CBV and reductions in binding potential that were localized to the dopamine-rich striatum. Moreover, similar temporal profiles were observed for specific binding estimates and changes in CBV. Injection of graded raclopride mass doses revealed a monotonic coupling between neurovascular responses and receptor occupancies. The distinct CBV magnitudes between putamen and caudate at matched occupancies approximately matched literature differences in basal dopamine levels, suggesting that the relative fMRI measurements reflect basal D2/D3 dopamine receptor occupancy. These results can provide a basis for models that relate dopaminergic occupancies to hemodynamic changes in the basal ganglia. Overall, these data demonstrate the utility of simultaneous PET/fMRI for investigations of neurovascular coupling that correlate neurochemistry with hemodynamic changes in vivo for any receptor system with an available PET tracer.