EVALUATION OF SPINAL CORD WHITE MATTER INJURY USING DTI

使用 DTI 评估脊髓白质损伤

• 批准号: 8079705
• 负责人: SHENG-KWEI SONG
• 金额: $ 41.49万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8079705
• 关键词: Acute; Address; Amyloid beta-Protein Precursor; Animals; Axon; Behavioral; Biological Markers; Biological Preservation; Cervical; Cervical spinal cord structure; Classification; Clinical; Consultations; Corticospinal Tracts; Demyelinations; Diffusion Magnetic Resonance Imaging; Distal; Electrophysiology (science); Evaluation; Experimental Designs; Experimental Models; Fiber; Follow-Up Studies; Functional disorder; Future; Goals; Health; Histology; Hospitals; Hour; Human; Immunohistochemistry; Impairment; Individual; Injury; International; Ischemia; Lateral; Lead; Lesion; Location; Magnetism; Measurement; Measures; Medical; Membrane; Modeling; Motor; Mus; Myelin; Myelin Basic Proteins; Neuraxis; Neurologic; Neurological outcome; Ohio; Operative Surgical Procedures; Outcome; Outcome Measure; Pathology; Patients; Perfusion; Phase; Physiological; Play; Radial; Rattus; Recovery of Function; Recruitment Activity; Rodent Model; Role; Sensory; Severities; Shivering; Spinal Cord Diseases; Spinal Cord Lesions; Spinal cord injury; Spinal cord injury patients; Stratification; Structure; Surgical Decompression; Surrogate Endpoint; Testing; Time; Tissues; Transgenic Mice; Translating; Translations; Trauma; Universities; Validation; Vertebral column; Wallerian Degeneration; Washington; clinical decision-making; disability; dorsal column; dysmyelination; efficacy testing; follower of religion Jewish; functional status; gray matter; improved; in vivo; interest; medical schools; mouse model; neurofilament; neurosurgery; psychologic; response; sample fixation; social; spinal cord white matter; water diffusion; white matter; white matter injury

DESCRIPTION (provided by applicant): Diffusion tensor imaging (DTI) measures the diffusion of water molecules, which reflects the microstructural organization of the tissues of interest. Previously, we have demonstrated that water diffusion parallel to the fibers, axial diffusivity, is much greater than that perpendicular to the fibers, radial diffusivity. We further demonstrated that demyelination leads to an increase in radial diffusivity and axonal damage leads to a decrease in axial diffusivity in mouse models of white matter injuries. In this proposal, we hypothesized that the in vivo DTI biomarker of axonal injury, i.e., decreased axial diffusivity, may serve as an early and accurate surrogate endpoint for outcome prediction in spinal cord injury (SCI). Axonal damage occurring in the acute period following SCI is the primary cause of long-term neurological disabilities in SCI. Thus, the primary goal of the proposed study is to determine at what post-injury time points can DTI be used to accurately predict functional (behavioral and electrophysiological) outcomes in rodent models of SCI. A translation of the use of DTI biomarker of axonal injury to cervical spondylotic myelopathy (CSM) patients will also be pursued to test the efficacy of this marker in the clinical setting. Three key questions are asked: (1) Does the in vivo DTI axonal injury biomarker reflect the underlying structural changes and predict long-term neurological outcome in SCI mice? (2) Do the in vivo DTI biomarkers correlate with axon function as measured with in vivo electrophysiology? (3) Do the in vivo DTI biomarkers accurately correlate with neurological disabilities in human cervical spondylotic myelopathy (CSM) patients? These questions will be addressed by performing the mechanistic assessment of the in vivo DTI derived biomarker of axonal injury and its application as the outcome predictor of SCI using YFP and shiverer-YFP mice (Aim 1), functional correlation of in vivo DTI biomarker of axonal injury with electrophysiology (Aim 2), and the human translation of this biomarker to CSM patients (Aim 3). PUBLIC HEALTH RELEVANCE: Spinal cord injury (SCI) can lead to devastating medical, psychological, social, and financial consequences. Experimental strategies that focus on white matter preservation during the hyperacute phase hold the greatest potential for functional recovery following traumatic SCI. The successful application of the proposed in vivo diffusion tensor imaging biomarker of white matter in the proposed studies will offer a more accurate prognostication and improved treatment stratification for SCI patients.

描述(申请人提供)：扩散张量成像(DTI)测量水分子的扩散，这反映了感兴趣组织的微观结构组织。以前，我们已经证明了水在平行于纤维的扩散系数，轴向扩散系数，远大于垂直于纤维的径向扩散系数。我们进一步证明，在白质损伤的小鼠模型中，脱髓鞘导致径向弥散系数增加，轴突损伤导致轴向弥散系数降低。在这项建议中，我们假设轴突损伤的体内DTI生物标记物，即轴向弥散系数降低，可以作为脊髓损伤(SCI)预后预测的早期和准确的替代终点。脊髓损伤后急性期发生的轴突损伤是导致脊髓损伤后长期神经功能障碍的主要原因。因此，本研究的主要目的是确定在脊髓损伤的啮齿动物模型中，什么时间点的DTI可以准确地预测功能(行为和电生理)结果。DTI轴突损伤生物标记物在脊髓型颈椎病(CSM)患者中的应用也将在临床环境中测试该标记物的有效性。提出了三个关键问题：(1)体内DTI轴突损伤生物标记物是否反映了脊髓损伤小鼠潜在的结构变化并预测其长期神经预后；(2)体内DTI生物标记物是否与体内电生理学测量的轴突功能相关？(3)体内DTI生物标记物是否准确地与人类脊髓型颈椎病(CSM)患者的神经功能障碍相关？这些问题将通过对体内DTI衍生的轴突损伤生物标记物的机械评估及其作为脊髓损伤预后预测因子的应用(目标1)、轴突损伤体内DTI生物标记物与电生理学的功能相关性(目标2)以及该生物标记物在CSM患者中的人类翻译(目标3)来解决。公共卫生相关性：脊髓损伤(SCI)可导致毁灭性的医疗、心理、社会和经济后果。侧重于超急性期脑白质保护的实验策略对创伤性脊髓损伤后的功能恢复具有最大的潜力。所提出的脑白质体内扩散张量成像生物标记物的成功应用将为脊髓损伤患者提供更准确的预测和改善的治疗分层。