Diffusion tensor imaging of the injured spinal cord

受损脊髓的弥散张量成像

• 批准号: 7748471
• 负责人: Shekar N. Kurpad
• 金额: --
• 依托单位: CLEMENT J. ZABLOCKI VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-10-01 至 2012-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7748471
• 关键词: Animals; Behavioral; Caring; Cell physiology; Cells; Cervical; Chest; Chronic; Clinical Research; Contusions; Data; Development; Diagnostic; Diagnostic tests; Diffusion; Diffusion Magnetic Resonance Imaging; Distant; Dorsal; Effectiveness; Engineering; Evoked Potentials; Family; Fiber; Flexor; Forelimb; Future; Goals; Healthcare; Hindlimb; Histologic; Histology; Human; Image; Image Analysis; Imaging Techniques; Implant; Injury; Intervention; Joints; Length; Lesion; Location; Magnetic Resonance Imaging; Manuscripts; Measurement; Measures; Mentorship; Military Personnel; Modeling; Monitor; Morphology; Motor Evoked Potentials; Natural regeneration; Nature; Neurons; Pain; Pathology; Patients; Pattern; Permeability; Persons; Physical therapy; Pilot Projects; Population; Postdoctoral Fellow; Process; Program Reviews; Property; Publications; Rattus; Recovery; Reflex action; Rehabilitation therapy; Research; Research Support; Resolution; Scanning; Sensorimotor functions; Services; Severities; Site; Somatosensory Evoked Potentials; Spinal; Spinal Cord; Spinal cord injury; Stem cells; Structure; Testing; Thoracic spinal cord structure; Time; Tissues; Translating; Transplantation; United States; Validation; Veterans; Work; allodynia; base; clinical care; dorsal horn; experience; functional status; graduate student; gray matter; in vivo; injured; interest; meetings; morphometry; novel; prognostic; public health relevance; regenerative; regenerative therapy; research and development; research study; response; sciatic nerve; spinal tract; tool

DESCRIPTION (provided by applicant): ABSTRACT Hypothesis: We hypothesize the diffusion properties and microstructure change across the entire length of the spinal cord during recovery from SCI. Also, we postulate that diffusion measurements and tissue sparing can be used to estimate sensorimotor function. In addition, we hypothesize that DTI is sensitive to regenerative interventions. Preliminary Data: Pilot studies have demonstrated the feasibility of obtaining DTI images of the injured and non-injured rat spinal cord using a high field (9.4T) small animal magnet. DTI images appear to follow expected patterns predicted by images obtained in chronic human SCI, with changes in diffusivity both at the injury site and in regions distant from the injury. Of particular note, reductions in diffusion appear in regions o fthe spinal cord distant from the injury site that correlate with histological data indicating cellular responses in neurons ofthe corresponding gray matter. Further, pilot data indicate that diffusion patterns are related to functional connectivity of the spinal cord, evidenced by correlations with spinal somatosensory evoked potentials (SSEPs). In separate studies, we have also demonstrated specific structural changes in the cervical dorsal hom of the rat spinal cord subjected to thoracic contusion injury and treated with stem cell grafts. These structural changes correlated with increased proliferation of pain fibers, which functionally resulted in the development of forelimb allodynia. We propose using this treatment paradigm, with well documented structural and functional changes, to test the diagnostic and prognostic abilities of DTI. Research Objectives: The overall goal of this project is to determine whether DTI can provide a non invasive imaging correlate of spinal cord structure and function following injury and regenerative therapies in a rat model of SCI. We plan to pursue this goal through three specific objectives. (1) Characterize region-specific changes in diffusivity during recovery from SCI. (2) Characterize functional correlates to DTI in the spinal cord during recovery from SCI. (3) Determine the sensitivity ofDTI to neuronal stem cell treatments following SCI. Our approach will use in vivo and ex vivo OTI to detemi.ine histological correlates during recovery from SCI. We will then determine the behavioral and electrophysiological functional correlates to DTI to histology and axonal morphometry. Lastly, we will determine the sensitivity of DTI to regeneration interventions with known changes in structure and function. The translational nature of this project is reflected by direct future application in humans if DTI is found to be able to detect histologically verifiable changes in morphology in the injured spinal cord. PUBLIC HEALTH RELEVANCE: Potential Impact on Veterans' Health Care: Spinal cord injury (SCI) constitutes one of the most devastating calamities that a person or their family can experience. With the United States currently engaged in several military efforts globally, SCI is likely to be an increasingly significant problem in the veteran population. This study will result in the validation of novel magnetic resonance imaging techniques (Diffusion Tensor Imaging, DTI) for monitoring the structural integrity and functional status of the spinal cord following an injury. We anticipate this information will prove vital to further understanding the pathology of SCI and establishing the use of DTI as an accurate, non-invasive diagnostic and prognostic tool. In addition, detailed information of the extent of injury and subsequent impact on sensorimotor function will prove invaluable in rehabilitative strategies involving pharmacological and physical therapies. We have focused in the last two years in the development and retention of a "team" approach to SCI treatment and imaging which uses experts in engineering (Dr Schmit), image acquisition and analysis (Dr Ulmer) and spinal cord interventions with stem cells (Dr Kurpad, Alexanian and Crowe). Dr Kurpad additionally is the Chief of the Neurosurgical Service at the Zablocki VA and has a strong interest in the clinical care of patients with SCI. This commitment to SCI clinical care and research is additionally reflected by his research support from the BL R&D MERIT Review Program. The presence of this "team" and the promising preliminary data that have culminated in five publications this year are expected to generate definitive data that can be translated successfully for the care of Veterans with SCI.

描述（由申请人提供）： 摘要假设：我们假设 SCI 恢复期间整个脊髓长度的扩散特性和微观结构发生变化。此外，我们假设扩散测量和组织保留可用于估计感觉运动功能。此外，我们假设 DTI 对再生干预敏感。初步数据：初步研究已经证明使用高场 (9.4T) 小动物磁铁获得受伤和未受伤大鼠脊髓的 DTI 图像的可行性。 DTI 图像似乎遵循慢性人类 SCI 中获得的图像预测的预期模式，损伤部位和远离损伤的区域的扩散率都发生变化。特别值得注意的是，扩散减少出现在远离损伤部位的脊髓区域，这与表明相应灰质神经元细胞反应的组织学数据相关。此外，试点数据表明，扩散模式与脊髓的功能连接相关，与脊髓体感诱发电位 (SSEP) 的相关性证明了这一点。在单独的研究中，我们还证明了遭受胸椎挫伤并接受干细胞移植治疗的大鼠脊髓颈背角的特定结构变化。这些结构变化与疼痛纤维增殖增加相关，这在功能上导致前肢异常性疼痛的发生。我们建议使用这种具有详细记录的结构和功能变化的治疗范例来测试 DTI 的诊断和预后能力。研究目标：该项目的总体目标是确定 DTI 是否可以在 SCI 大鼠模型损伤和再生治疗后提供与脊髓结构和功能相关的非侵入性成像。我们计划通过三个具体目标来实现这一目标。 (1) 表征 SCI 恢复期间扩散率的区域特定变化。 (2) 表征 SCI 恢复期间脊髓中与 DTI 的功能相关性。 (3)确定SCI后DTI对神经元干细胞治疗的敏感性。我们的方法将使用体内和离体 OTI 来确定 SCI 恢复期间的组织学相关性。然后我们将确定 DTI 与组织学和轴突形态测量的行为和电生理功能相关性。最后，我们将确定 DTI 对已知结构和功能变化的再生干预的敏感性。如果发现 DTI 能够检测到受损脊髓的组织学上可验证的形态变化，则该项目的转化性质将通过未来直接应用于人类来体现。 公共卫生相关性： 对退伍军人医疗保健的潜在影响：脊髓损伤 (SCI) 是个人或其家人可能经历的最具破坏性的灾难之一。由于美国目前在全球范围内开展多项军事行动，SCI 可能成为退伍军人中日益严重的问题。这项研究将验证新型磁共振成像技术（扩散张量成像，DTI），用于监测受伤后脊髓的结构完整性和功能状态。我们预计这些信息对于进一步了解 SCI 的病理学以及建立 DTI 作为准确、非侵入性的诊断和预后工具至关重要。此外，有关损伤程度以及随后对感觉运动功能的影响的详细信息将在涉及药物和物理治疗的康复策略中证明是非常有价值的。过去两年，我们致力于开发和保留 SCI 治疗和成像的“团队”方法，该方法使用工程专家（Schmit 博士）、图像采集和分析（Ulmer 博士）以及干细胞脊髓干预（ Kurpad 博士、Alexanian 和 Crowe）。 Kurpad 博士还是 Zablocki VA 神经外科服务的主管，对 SCI 患者的临床护理有着浓厚的兴趣。他对 SCI 临床护理和研究的承诺还体现在他对 BL 研发 MERIT 审查计划的研究支持上。这个“团队”的存在以及今年已发表五份出版物的充满希望的初步数据预计将产生明确的数据，这些数据可以成功转化用于护理患有 SCI 的退伍军人。