Detection of Live Fibers in Injured Spinal Cord

描述（由申请人提供）：磁共振成像（MRI）提供大鼠脊髓（SC）的体内3D图像，具有精细的软组织对比，并允许在实验性脊髓损伤（SCI）研究中纵向跟踪同一动物。然而，传统的MRI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。我们在之前的SCI研究中使用了MR造影剂，我们研究了锰增强MRI (MEI)，它有可能产生正常和受损脊髓中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）在正常脊髓的吻侧和尾侧均有扩散。在半切除的SCs中，Mn在病变的对侧转运，而不是在同侧转运。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，损伤内部和下方检测到Mn标记，可能是由于其中存在活组织。在最近的实验中，我们将锰注入正常和受伤大鼠的皮层或脑干。在皮质内注射时，在锥体下方的下降脊髓束中观察到弱标记。但是，脑干注射成功地在目标纤维中产生了敏感和特异性的标记。损伤下方的损伤脊髓切片用Mn标记，表明一些纤维在损伤处桥接。从这些方面来看，MEI提供了一种检测受损SC中活纤维（保留/恢复）的新工具，并可能在验证扩散张量成像（diffusion tensor imaging， DTI）检测这些纤维的准确性方面发挥作用。基于这些结果，我们假设DTI与MEI的验证可能为脊髓损伤恢复过程中纤维连接变化的时空动态提供重要信息。为了验证这一假设，我们建议使用MEI， DTI和高分辨率MRI以及神经行为测试和终点组织学分析来研究正常和受损的sc。这些多模态的研究将为探究脊髓损伤的演变和绘制纤维投射图谱提供一种新的模态。这将为未来的实验研究奠定基础，旨在测试促进纤维连接、理解SC可塑性和改善脊髓损伤后功能恢复的新疗法。

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.