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度，并允许在实验性脊髓损伤（SCI）研究中纵向跟踪同一动物。传统的MRI，但是，提供有限的信息和新的神经影像学方法需要可视化的神经网络受伤的SC。经验丰富的使用MR造影剂在我们以前的SCI研究，我们已经调查锰增强MRI（MEI）的潜力，以产生高分辨率地图的神经纤维预测在正常和受伤的脊髓。我们的初步数据表明，造影剂锰（Mn）扩散在两个吻和尾方向在正常的脊髓。在半切的SC，Mn被运输到对侧，但不是同侧，削减病变下方。这也证实了组织学神经元示踪剂的平行研究。在挫伤型SCI模型中，在损伤内和损伤下方检测到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Mn递送到正常和受伤大鼠的皮层或脑干中。皮质内注射时，在锥体交叉以下的下行脊髓束中观察到弱标记。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。损伤脊髓下方的部分用Mn标记，表明一些纤维桥接损伤。从这些方面来看，MEI为检测受损SC中的活纤维（备用/恢复）提供了一种新的工具，并可能在验证弥散张量成像（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证实与MEI可能提供关键信息的时空动态的纤维连接的变化过程中恢复SCI。为了验证这一假设，我们建议使用MEI，DTI和高分辨率MRI沿着神经行为测试和终点组织学分析来研究正常和受损的SC。这些多模式的研究将建立一个新的模式来探索SCI的演变和映射的纤维投射。这应该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SCI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.