用于活体追踪神经解剖连接的 MR 可见化合物的开发。
Development of a MR-visible compound for tracing neuroanatomical connections in vivo.
机构信息
Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20814, USA.
出版信息
Neuron. 2011 Apr 28;70(2):229-43. doi: 10.1016/j.neuron.2011.03.010.
Traditional studies of neuroanatomical connections require injection of tracer compounds into living brains, then histology of the postmortem tissue. Here, we describe and validate a compound that reveals neuronal connections in vivo, using MRI. The classic anatomical tracer CTB (cholera-toxin subunit-B) was conjugated with a gadolinium-chelate to form GdDOTA-CTB. GdDOTA-CTB was injected into the primary somatosensory cortex (S1) or the olfactory pathway of rats. High-resolution MR images were collected at a range of time points at 11.7T and 7T. The transported GdDOTA-CTB was visible for at least 1 month post-injection, clearing within 2 months. Control injections of non-conjugated GdDOTA into S1 were not transported and cleared within 1-2 days. Control injections of Gd-Albumin were not transported either, clearing within 7 days. These MR results were verified by classic immunohistochemical staining for CTB, in the same animals. The GdDOTA-CTB neuronal transport was target specific, monosynaptic, stable for several weeks, and reproducible.
传统的神经解剖连接研究需要将示踪化合物注入活体大脑，然后对死后组织进行组织学研究。在这里，我们描述并验证了一种可通过 MRI 显示体内神经元连接的化合物。经典的解剖示踪剂 CTB（霍乱毒素亚单位-B）与钆螯合物缀合形成 GdDOTA-CTB。将 GdDOTA-CTB 注射到大鼠的初级体感皮层（S1）或嗅觉通路中。在 11.7T 和 7T 下，在一系列时间点收集高分辨率的 MR 图像。注射后至少 1 个月内可观察到转运的 GdDOTA-CTB，2 个月内清除。在 S1 中注射非缀合的 GdDOTA 的对照注射不会转运，并且在 1-2 天内清除。Gd-Albumin 的对照注射也没有转运，在 7 天内清除。在相同的动物中，通过 CTB 的经典免疫组织化学染色验证了这些 MR 结果。GdDOTA-CTB 神经元转运具有靶向特异性、单突触性、数周内稳定且可重复。
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