Spinal and Cerebral biomarkers for measuring disease progression and prognosis in chronic spinal cord injury

项目摘要/摘要 退行性腰椎间盘疾病，一个经常被称为脊椎病的术语，发生在 正常的老化过程及其治疗费用每年高达数十亿美元。宫颈 脊髓型脊髓病(CSM)是慢性脊髓损伤(SCI)的一种，是最使人虚弱的 一种退行性椎间盘疾病，是脊髓最常见的获得性原因 年龄大于50岁的成年人的功能障碍。在许多方面，它对社会的影响更大 而不是创伤性脊髓损伤，因为患有这种疾病的患者数量要多得多。 在我们对CSM发病机制和治疗的理解中，有几个关键的差距，部分 由于绝大多数CSM研究都是孤立地研究脊髓， 而没有分析中枢神经系统内的其他棘上结构，这些结构在解剖学和 在功能上相互关联的。此外，许多这些孤立的颈椎研究已经利用 标准MRI，它提供了极好的宏观细节，但几乎没有关于 脊髓微结构、细胞生理学或新陈代谢。 最近的研究表明，大脑重组和神经可塑性的作用 创伤性脊髓损伤后维持神经功能的代偿机制。我们有 先前阐明了在CSM患者中使用基于任务和休息的类似发现 功能核磁共振。在我们之前的资助期间，我们建立了扩散张量成像和 磁共振波谱作为评估脊髓微结构的合适技术 生物化学，并显示这些生物标志物与神经学程度的相关性 减损。我们现在建议在以前工作的基础上开发一种多模式 探讨脊柱上可塑性对CSM发病机制和预后的影响 在先进的脊髓成像技术MRS和DTI的配合下恢复 整个感觉运动网络的完整视图。除了极大地提高我们的知识 对于慢性脊髓损伤的发病机制和康复，我们寻求利用这些先进的 弥合当前CSM患者监测中临床差距的影像技术 非手术，以及对那些接受手术治疗的人的手术结果的预测。

Project Summary/Abstract Degenerative disc disease, a term frequently referred to as spondylosis, occurs as part of the normal aging process and its treatment costs run in the many billions of dollars per year. Cervical spondylotic myelopathy (CSM), a form of chronic spinal cord injury (SCI), is the most debilitating type of degenerative disc disease, and is the most common acquired cause of spinal cord dysfunction in adults greater than 50 years of age. In many ways, its impact on society is greater than traumatic SCI due to the substantially larger number of patients afflicted with this disorder. There are several critical gaps in our understanding of CSM pathogenesis and treatment, in part due to the fact that the vast majority of CSM research has investigated the spinal cord in isolation, and not assayed other supraspinal structures within the CNS that are anatomically and functionally interrelated. Moreover, many of these isolated cervical spine studies have utilized standard MRI, which provides excellent macroscopic detail, but little information regarding the spinal cord microstructure, cellular physiology, or metabolism. Recent studies have demonstrated the role of cerebral reorganization and neural plasticity as compensatory mechanisms to preserve neurological function following traumatic SCI. We have previously elucidated similar findings in CSM patients utilizing both task based and resting functional MRI. During our previous funding period, we established Diffusion Tensor Imaging and MR spectroscopy as suitable techniques for assessing the spinal cord microstructure and biochemistry, and demonstrated correlations with these biomarkers to degree of neurological impairment. We now propose to build upon our previous work by developing a multi-modality imaging paradigm that probes the impact of supraspinal plasticity on CSM pathogenesis and recovery in tandem with advanced spinal cord imaging techniques MRS and DTI to yield a complete view of the entire sensorimotor network. In addition to greatly enhancing our knowledge base regarding chronic SCI pathogenesis and recovery, we seek to utilize these advanced imaging techniques to bridge current clinical gaps in the monitoring of CSM patients managed nonoperatively, as well as prediction of surgical outcome in those treated with surgery.