Detection of Live Fibers in Injured Spinal Cord

描述(申请人提供)：磁共振成像(MRI)提供了大鼠脊髓(SC)的活体3D图像，具有精致的软组织对比，并允许在实验性脊髓损伤(SCI)研究中纵向跟踪相同的动物。然而，传统的磁共振成像提供的信息有限，需要新的神经成像方法来可视化受损SC的神经网络。在我们以前的脊髓损伤研究中使用磁共振造影剂的经验，我们研究了锰增强磁共振成像(MEI)，有可能产生正常和损伤脊髓神经纤维投射的高分辨率地图。我们的初步数据显示，造影剂锰(Mn)在正常脊髓中沿吻侧和尾侧两个方向扩散。在半切的SCs中，Mn被运输到伤口对侧的病变下方，但不是同侧。组织学神经元示踪剂的平行研究也证实了这一点。在挫伤型脊髓损伤模型中，在损伤内和损伤下检测到了MN标记，这可能是由于其中存在活组织。在最近的实验中，我们将锰输送到正常和损伤大鼠的大脑皮层或脑干中。皮质内注射，在锥体交叉下方的下行脊髓束观察到弱标记。但是，脑干注射成功地在靶纤维中产生了敏感和特异的标记。损伤下方脊髓损伤段用锰标记，提示部分纤维跨损伤桥接。从这些方面来看，MEI提供了一种新的工具来检测受损SC中的存活纤维(备用/修复)，并可能在验证弥散张量成像(DTI)在感知这些纤维方面的准确性方面发挥作用。基于这些结果，我们推测，与MEI证实的DTI可能为脊髓损伤恢复过程中纤维连接变化的时空动力学提供了重要信息。为了验证这一假设，我们建议使用MEI、DTI和高分辨率MRI结合神经行为测试和终点组织学分析来研究正常和损伤的SCs。这些多模式研究将建立一种新的模式来探索脊髓损伤的演变并绘制纤维投射图。这将为未来的实验研究奠定基础，旨在测试促进纤维连接的新疗法，了解SC的可塑性，并改善脊髓损伤后的功能恢复。

DESCRIPTION (provided by applicant): Magnetic resonance imaging (MRI) provides in vivo 3D images of rat spinal cord (SC) with exquisite soft tissue contrast, and allows following the same animal longitudinally in experimental spinal cord injury (SCI) studies. Conventional MRIs, however, give limited information and new neuroimaging methods are required for visualizing the neural network of injured SC. Experienced with the use of MR contrast agents in our previous SCI studies, we have investigated manganese-enhanced MRI (MEI) with the potential to produce high-resolution maps of the neural fiber projections in normal and injured cords. Our initial data showed that the contrast agent manganese (Mn) spreads in both rostral and caudal directions in normal cord. In hemisectioned SCs, Mn is transported below the lesion on the contra-lateral, but not ipsilateral, to the cut. This was also confirmed by parallel studies with histological neuronal tracer. In a contusion-type SCI model, Mn labeling was detected within and below the injury, possibly due to the presence of viable tissue therein. In recent experiments, we delivered Mn into the cortex or brainstem of normal and injured rats. With intracortical injection, weak labeling was observed in the descending spinal tracts below the pyramidal decussation. But, injection to brainstem successfully produced sensitive and specific labeling in the targeted fibers. The sections of injured cord below the injury were labeled with Mn, suggesting some fibers were bridging across the injury. From these aspects, MEI offers a new tool for detecting live fibers (spared/restored) in injured SC, and may play a role in validating the accuracy of diffusion tensor imaging (DTI) in sensing these fibers. Based on these results, we hypothesize that DTI corroborated with MEI may provide crucial information on the spatiotemporal dynamics of the changes in the fiber connections during the course of recovery from SCI. To test this hypothesis, we propose to investigate normal and injured SCs using MEI, DTI and high resolution MRI along with neurobehavioral tests and end point histological analysis. These multi-modal studies will establish a new modality to probe the evolution of SCI and map the fiber projections. This should form a basis for future experimental investigations aimed at testing new therapies for promoting fiber connectivity, understanding SC plasticity and improving functional recovery from SCI.