In Vivo Imaging of Brain Connectivity

描述（由申请人提供）：连通性对于理解大脑如何工作至关重要。目前，大多数连接性数据是在死后组织学研究中获得的，这是劳动密集型的，需要使用许多动物，并且每只动物只能进行一次。磁共振成像方法提供了更高的效率，并且因为它们完全在体内进行，所以可以根据需要在同一动物上重复。扩散张量成像可用于研究人类大脑的连通性，但在动物中，通过将MR透明示踪物质直接注射到连通性有问题的大脑区域，可以获得更高的分辨率和特异性。锰已被用于大鼠和鸟类的这一目的，并已被用于跟踪猴子的大皮层下连接。 我们建议开发一种方法来研究详细的皮质连接在生活的灵长类动物，使用脑锰注射加上MRI分析和可视化。我们将优化注射技术，数据采集和后处理的皮质内和皮质下的投影。为了验证我们的研究结果，我们将共同注射锰与组织学示踪剂，然后比较标准的死后组织学分析的结果与锰增强MRI数据。 这种方法的成功开发可能会彻底改变猴子连通性的研究，例如，允许精确确定皮层在发育，技能获得和损伤恢复中如何重新连接。它还将有助于确定与生理决定功能相关的区域边界，并有可能大大增加我们对大脑回路如何处理信息的理解。也许这项工作对健康的最大影响将是脑损伤后的康复，因为这种方法将使我们能够在个体受试者对脑损伤做出反应并从中恢复或无法从脑损伤中恢复时询问大脑连接。

DESCRIPTION (provided by applicant): Connectivity is critical to understanding how the brain works. Currently, most connectivity data is obtained in post-mortem histology studies, which are labor intensive, require the use of many animals, and can only be performed once per animal. Magnetic resonance imaging methods offer much increased efficiency and, because they are performed entirely in vivo, can be repeated as often as desired on the same animal. Diffusion tensor imaging is useful for studying brain connectivity in humans, but in animals, increased resolution and specificity can be obtained by injecting an MR-lucent tracer substance directly into the brain area whose connectivity is in question. Manganese has been used for this purpose in rats and birds, and has been used to trace large subcortical connections in monkeys. We propose to develop a methodology for studying detailed cortical connectivity in living primates, using cerebral manganese injections coupled with MRI analysis and visualization. We will optimize injection techniques, data acquisition and post-processing for intracortical and cortical-subcortical projections. In order to validate our results, we will co-inject manganese with histologic tracers and then compare the results of standard post-mortem histologic analysis with the manganese-enhanced MRI data. Successful development of this method could revolutionize the study of connectivity in monkeys, permitting, for example, precise determinations of how the cortex is rewired in development, skill acquisition and in recovery from lesions. It will also facilitate determinations of areal boundaries in relation to physiologically determined functions, and has the potential to greatly increase our understanding of how circuits in the brain process information. Perhaps the greatest health-related impact of this work will be on rehabilitation after brain injury, since this method will allow us to interrogate brain connectivity as individual subjects respond to and recover from, or fail to recover from, brain insults.