EVALUATION OF SPINAL CORD WHITE MATTER INJURY USING DTI

使用 DTI 评估脊髓白质损伤

• 批准号: 8279436
• 负责人: SHENG-KWEI SONG
• 金额: $ 41.28万
• 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/8279436
• 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（由申请人提供）：扩散张量成像（DTI）测量水分子的扩散，这反映了感兴趣的组织的微结构组织。以前，我们已经证明了与纤维平行的水扩散，轴向扩散率远大于垂直于纤维，径向扩散率的水扩散。我们进一步证明，脱髓鞘会导致径向扩散率的升高和轴突损伤导致白质损伤小鼠模型中轴向扩散率的降低。在此提案中，我们假设轴突损伤的体内DTI生物标志物，即轴向扩散率降低，可以作为脊髓损伤结果预测（SCI）的早期且准确的替代端点。 SCI后急性时期发生的轴突损伤是SCI长期神经残疾的主要原因。因此，拟议的研究的主要目标是确定在伤害后时间点可以使用DTI来准确预测SCI啮齿动物模型中的功能（行为和电生理）结果。还将追求将轴突损伤的DTI生物标志物转换为颈椎脊髓病（CSM）患者的转换，以测试该标志物在临床环境中的功效。提出了三个关键问题：（1）体内DTI轴突损伤生物标志物是否反映了基本的结构变化并预测SCI小鼠的长期神经学结果？ （2）体内生物标志物是否与体内电生理学测量的轴突功能相关？ （3）体内DTI生物标志物是否与人宫颈脊柱脊髓病（CSM）患者的神经疾病准确相关？这些问题将通过对轴突损伤的生物标志物进行机械评估，并使用YFP和Shiverer-YFP小鼠作为SCI的结果预测因子（AIM 1），在体内生物学损伤与电子生理学（AIM 2）和人类翻译（AIM 2）的功能相关。公共卫生相关性：脊髓损伤（SCI）可能导致毁灭性的医疗，心理，社会和财务后果。在超急性期期间关注白质保存的实验策略具有创伤性SCI后功能恢复的最大潜力。在拟议的研究中，拟议的白质的体内扩散张量成像生物标志物的成功应用将为SCI患者提供更准确的预后和改进的治疗分层。