Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20814, USA.
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。
