Diffusion Tensor Imaging of the Injured Spinal Cord

损伤脊髓的弥散张量成像

• 批准号: 8783631
• 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: 2014
• 资助国家: 美国
• 起止时间: 2014-10-01 至 2018-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8783631
• 关键词: Acute; Architecture; Astrocytes; Axon; Biological; Biological Markers; Caring; Cervical; Cervical spinal cord structure; Chest; Clinical; Clinical Research; Contusions; Data; Demyelinations; Detection; Diagnosis; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Distant; Edema; Exhibits; Experimental Models; Functional Magnetic Resonance Imaging; Goals; Gold; Histopathology; Human; Image; Imaging Techniques; Injury; Intervention; Knowledge; MRI Scans; Magnetic Resonance Imaging; Measures; Methods; Metric; Modeling; Monitor; Morphologic artifacts; Nervous System Physiology; Nervous System Trauma; Neurologic Examination; Outcome; Patient Monitoring; Patients; Pre-Clinical Model; Prognostic Marker; Rattus; Recovery; Recovery of Function; Research; Residual state; Sensitivity and Specificity; Severities; Signal Transduction; Site; Spinal; Spinal Cord; Spinal cord injury; Surrogate Markers; Techniques; Testing; Therapeutic Intervention; Thoracic Injuries; Thoracic spinal cord structure; Time; Tissues; Translating; Translations; Validation; Vertebral column; Veterans; Weight; axonal degeneration; base; experience; functional outcomes; improved; in vivo; indexing; injured; innovation; interdisciplinary approach; nerve injury; novel; novel strategies; preclinical study; prognostic; public health relevance; sample fixation; spinal cord imaging; stem; therapy design; tool; white matter

DESCRIPTION: Rationale and Preliminary Data: We will conduct a validation and characterization of the diffusion tensor imaging changes and histopathology of the cervical spinal cord following experimental thoracic contusion injury. Conventional MRI scans to detect edema using T2-weighted imaging are no better at predicting the degree of recovery in patients with spinal cord injury (SCI) than a traditional neurological examination. Diffusion tensor imaging (DTI) is showing promise as a prognostic imaging biomarker in SCI. However, DTI at the injury site is often hampered by artifacts from spinal fixation hardware. Our preclinical studies in the rat have demonstrated robust DTI alterations in the high cervical spinal cord (hcDTI) that correlate with injury severity and functional recovery. Thus, our preliminary data indicates that diffusivity in te high cervical spinal cord, as measured by DTI, is a potential biomarker of neural injury in SCI. While promising, a more comprehensive validation is necessary for accurate diagnosis in human SCI. To that end, we will employ our preclinical model of thoracic contusion injury to advance the understanding of the DTI changes in the cervical cord as markers of injury. Hypothesis and Specific Aims: We hypothesize that advanced MRI of the high cervical spinal cord is an accurate biomarker of tissue damage and injury severity that is prognostic of outcome. To examine this hypothesis, we will employ a rat model of thoracic contusion spinal cord injury and perform in vivo MRI, functional assessments, and histopathology. We will test our hypothesis by performing diffusion kurtosis imaging (DKI) and quantitative T2 (qT2) to improve the prognostic ability in the acute setting (Aim 1), establish these measures as a surrogate maker of tissue damage at the site of injury (Aim 2), and elucidate the pathophysiological mechanisms of MRI changes remote from the site of injury using gold-standard histopathology (Aim 3). To accomplish these aims, a multidisciplinary approach using in vivo DKI and qT2, quantitative histopathological analysis, and functional assessments will provide a comprehensive understanding of the relationship between noninvasive imaging markers and their biological underpinnings and functional implications. We hypothesize that detection of injury in the acute setting will be enhanced by DKI and qT2 MRI techniques. Furthermore, it is believed that the cervical cord DTI changes accurately reflect the degree of injury at the site of injury assessed by the amount of spared white matter. Finally, it is postulatd that in addition to axonal degeneration and demyelination, astrocyte reactivity is a prominent feature of injury that occurs distant from the injury and relates to the degree of functional recovery. Collectively, these studies will establish and validate hcDTI as a sensitive biomarker of SCI with the potential to improve prognostication and will guide translation to human SCI.

产品说明： 基本原理和初步数据：我们将对实验性胸部挫伤后颈髓的扩散张量成像变化和组织病理学进行验证和表征。在预测脊髓损伤（SCI）患者的恢复程度方面，使用T2加权成像检测水肿的常规MRI扫描并不比传统的神经系统检查更好。扩散张量成像（DTI）显示出作为SCI预后成像生物标志物的前景。然而，损伤部位的DTI经常受到脊柱固定硬件伪影的阻碍。我们在大鼠中的临床前研究已经证明了与损伤严重程度和功能恢复相关的高颈段脊髓（hcDTI）中的稳健DTI改变。因此，我们的初步数据表明，在高颈脊髓扩散，如DTI测量，是一个潜在的生物标志物的神经损伤在SCI。虽然有希望，但更全面的验证对于人类SCI的准确诊断是必要的。为此，我们将采用我们的临床前模型的胸部挫伤损伤，以促进理解的DTI变化在颈髓损伤的标志物。假设和具体目标：我们假设，高级MRI高颈脊髓是一个准确的生物标志物的组织损伤和损伤的严重程度，是预后的结果。为了检验这一假设，我们将采用大鼠模型的胸挫伤脊髓损伤，并进行体内MRI，功能评估，和组织病理学。我们将通过进行弥散峰度成像（DKI）和定量T2（qT2）来检验我们的假设，以提高急性环境中的预后能力（目标1），将这些措施作为损伤部位组织损伤的替代标志物（目标2），并使用金标准组织病理学来阐明远离损伤部位的MRI变化的病理生理学机制（目标3）。为了实现这些目标，使用体内DKI和qT2、定量组织病理学分析和功能评估的多学科方法将全面了解非侵入性成像标记物及其生物学基础和功能影响之间的关系。我们假设DKI和qT2 MRI技术将增强急性环境中损伤的检测。此外，据信颈髓DTI的变化准确地反映了损伤部位的损伤程度，通过备用白色物质的量来评估。最后，据推测，除了轴突变性和脱髓鞘，星形胶质细胞反应性是损伤的一个突出特征，发生在远离损伤的地方，并与功能恢复的程度有关。总的来说，这些研究将建立和验证hcDTI作为SCI的敏感生物标志物，具有改善诊断的潜力，并将指导人类SCI的翻译。