In Vivo Imaging of Brain Connectivity

描述（由申请人提供）：连接是理解大脑如何工作的关键。目前，大多数连通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。磁共振成像方法的效率大大提高，而且由于它们完全是在体内进行的，因此可以在同一只动物身上尽可能多地重复。扩散张量成像对于研究人类大脑的连通性是有用的，但是在动物中，通过直接向连通性有问题的大脑区域注射核磁共振示踪物质，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研究，并被用于追踪猴子皮层下的大连接。

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.