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）： 抽象假设：我们假设从SCI恢复期间，整个脊髓的扩散特性和微观结构变化。同样，我们假设扩散测量和避免组织可用于估计感觉运动功能。此外，我们假设DTI对再生干预措施敏感。初步数据：初步研究表明，使用高场（9.4t）小动物磁铁获得受伤和未造成的大鼠脊髓的DTI图像的可行性。 DTI图像似乎遵循在慢性人类SCI中获得的图像预测的预期模式，损伤部位和远离伤害区域的扩散率都有变化。特别值得注意的是，扩散的减少出现在远离损伤部位的脊髓的区域，该区域与表明相应灰质神经元的细胞反应相关的损伤部位。此外，试点数据表明，扩散模式与脊髓的功能连通性有关，这证明了与脊柱体感诱发电位（SSEP）的相关性。在单独的研究中，我们还证明了脊髓脊髓的宫颈背部的特定结构变化，受到胸骨挫伤损伤并用干细胞移植物处理。这些结构变化与疼痛纤维增殖的增加相关，这在功能上导致了前肢异常性疾病的发展。我们建议使用这种治疗范式具有充分的结构和功能变化，以测试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大鼠模型中受伤和再生疗法后的脊髓结构和功能的非侵入性成像相关。我们计划通过三个特定目标来实现这一目标。 （1）表征从SCI恢复期间扩散率的区域特异性变化。 （2）在从SCI中恢复过程中，表征功能与脊髓中的DTI相关。 （3）确定SCI后DTI对神经元干细胞处理的敏感性。我们的方法将使用体内和离体OTI来检测从SCI恢复期间的组织学相关。然后，我们将确定与DTI与组织学和轴突形态计量学的行为和电生理功能相关。最后，我们将确定DTI对再生干预措施的敏感性，并具有已知的结构和功能变化。如果发现DTI能够检测受损伤脊髓中形态学的组织学可验证的变化，则该项目的翻译性质反映在人类中。 公共卫生相关性： 对退伍军人的医疗保健的潜在影响：脊髓损伤（SCI）构成了一个人或其家人可以体验到的最具破坏性的灾难之一。由于美国目前在全球进行了几项军事努力，因此在退伍军人人口中，SCI可能是一个越来越重大的问题。这项研究将导致验证新型磁共振成像技术（扩散张量成像，DTI），以监测损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理解SCI的病理并确定DTI作为准确，无创诊断和预后工具至关重要。此外，在涉及药理和物理疗法的康复策略中，损伤程度以及随后对感觉运动功能的影响的详细信息将是无价的。在过去的两年中，我们专注于使用工程专家（Schmit博士），图像获取和分析（ULMER博士）和干细胞的脊髓干预（Kurpad，Alexanian和Crowe）的“团队”方法的SCI治疗和成像。 Kurpad博士还是Zablocki VA神经外科服务的负责人，对SCI患者的临床护理非常感兴趣。 BL R＆D优异审查计划的研究支持还反映了对SCI临床护理和研究的承诺。预计今年在五个出版物中达到顶峰的“团队”的存在以及有希望的初步数据将产生确定的数据，这些数据可以成功地转化为SCI的退伍军人。