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

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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.