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

用于测量慢性脊髓损伤疾病进展和预后的脊髓和大脑生物标志物

• 批准号: 10368062
• 负责人: Benjamin M. Ellingson
• 金额: $ 38.81万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-26 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10368062
• 关键词: Adult; Age-Years; Anatomy; Anisotropy; Area; Atrophic; Biochemistry; Biological Assay; Biological Markers; Brain; Cell physiology; Cerebrum; Cervical; Cervical spinal cord structure; Cervical spine; Chronic; Clinical; Complex; Corticospinal Tracts; Diffuse; Diffusion Magnetic Resonance Imaging; Disease; Disease Progression; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Goals; Imaging Techniques; Impairment; Individual; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measurement; Measures; Metabolic; Metabolism; Monitor; Motor; Multimodal Imaging; Neck Pain; Nervous System Physiology; Neuraxis; Neurologic; Neuronal Plasticity; Operative Surgical Procedures; Pain; Pathogenesis; Patients; Process; Prognosis; Recovery; Research; Rest; Role; Running; Societies; Spinal; Spinal Cord; Spinal Cord Diseases; Spinal cord injury; Spondylosis; Structure; Techniques; Thick; Treatment Cost; Vertebral column; Work; base; cerebral atrophy; disease prognosis; intervertebral disk degeneration; knowledge base; neuroimaging; neurological recovery; normal aging; postoperative recovery; preservation; relating to nervous system; response; spectroscopic imaging; spinal cord imaging; surgery outcome

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.

项目总结/摘要 退行性椎间盘疾病，一个经常被称为椎关节强硬的术语，作为关节炎的一部分发生。 正常的老化过程及其治疗费用每年高达数十亿美元。宫颈 脊髓型颈椎病（CSM）是一种慢性脊髓损伤（SCI）， 一种退行性椎间盘疾病，是脊髓损伤最常见的后天性原因。 50岁以上的成年人的功能障碍。在许多方面，它对社会的影响更大 创伤性脊髓损伤的患者人数要多得多。 在我们对CSM发病机制和治疗的理解中有几个关键的差距，部分原因是 由于绝大多数CSM研究已经单独研究了脊髓， 而没有分析CNS内的其他脊髓上结构， 功能上相互关联。此外，许多这些孤立的颈椎研究利用了 标准MRI，其提供了极好的宏观细节，但关于 脊髓微结构、细胞生理学或代谢。 最近的研究表明，大脑重组和神经可塑性的作用， 创伤性脊髓损伤后保护神经功能的代偿机制。我们有 先前阐明的CSM患者使用基于任务和休息的类似结果 功能性磁共振成像在我们之前的资助期间，我们建立了弥散张量成像， 磁共振波谱作为评估脊髓显微结构的合适技术， 生物化学，并证明与这些生物标志物的相关性，以神经系统的程度， 损伤我们现在提议在我们以前工作的基础上， 探讨脊髓上可塑性对脊髓型颈椎病发病机制的影响， 结合先进的脊髓成像技术MRS和DTI， 整个感觉运动网络的全貌。除了大大提高我们的知识 基于慢性SCI发病机制和恢复，我们寻求利用这些先进的 影像学技术，以弥补目前的临床差距，在监测CSM患者管理 非手术，以及预测手术治疗的手术结果。

项目成果

Spinal Cord Signal Intensity Predicts Functional Outcomes in the Operative Management of Degenerative Cervical Myelopathy.

脊髓信号强度可预测退行性脊髓型颈椎病手术治疗中的功能结果。

• DOI: 10.1097/bsd.0000000000001479
• 发表时间: 2023
• 期刊: Clinical spine surgery
• 影响因子: 1.9
• 作者: Firempong,GaylinnKwame;Sheppard,WilliamL;Gelfand,Yaroslav;Ellingson,BenjaminM;Holly,LangstonT
• 通讯作者: Holly,LangstonT

Compensatory brainstem functional and structural connectivity in patients with degenerative cervical myelopathy by probabilistic tractography and functional MRI.

• DOI: 10.1016/j.brainres.2020.147129
• 发表时间: 2020-12-15
• 期刊: Brain research
• 影响因子: 2.9
• 作者: Wang C;Laiwalla A;Salamon N;Ellingson BM;Holly LT
• 通讯作者: Holly LT

Spinal Cord Perfusion MR Imaging Implicates Both Ischemia and Hypoxia in the Pathogenesis of Cervical Spondylosis.

• DOI: 10.1016/j.wneu.2019.04.253
• 发表时间: 2019-08
• 期刊: World neurosurgery
• 影响因子: 2
• 作者: Ellingson BM;Woodworth DC;Leu K;Salamon N;Holly LT
• 通讯作者: Holly LT

Pathophysiology, classification, and MRI parallels in microvascular disease of the heart and brain.

心脏和大脑微血管疾病中的病理生理，分类和MRI相似。

• DOI: 10.1111/micc.12648
• 发表时间: 2020-11
• 期刊: Microcirculation (New York, N.Y. : 1994)
• 作者: Thomas MA;Hazany S;Ellingson BM;Hu P;Nguyen KL
• 通讯作者: Nguyen KL

Sex-Dependent Cortical Volume Changes in Patients with Degenerative Cervical Myelopathy.

• DOI: 10.3390/jcm10173965
• 发表时间: 2021-09-01
• 期刊: Journal of clinical medicine
• 影响因子: 3.9
• 作者: Oughourlian TC;Wang C;Salamon N;Holly LT;Ellingson BM
• 通讯作者: Ellingson BM