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.

描述： 基本原理和初步数据：我们将对实验性胸骨挫伤损伤后的扩散张量成像变化和颈脊髓的组织病理学进行验证和表征。常规的MRI扫描使用T2加权成像检测水肿，在预测脊髓损伤患者（SCI）的恢复程度上，不如传统的神经系统检查更好。扩散张量成像（DTI）在SCI中表现为预后成像生物标志物。但是，受伤部位的DTI通常受到脊柱固定硬件的工件的阻碍。我们在大鼠中的临床前研究表明，高宫颈脊髓（HCDTI）的强大DTI改变与损伤的严重程度和功能恢复相关。因此，我们的初步数据表明，通过DTI测量的高颈脊髓的扩散是SCI神经损伤的潜在生物标志物。在有希望的同时，对于人类科学的准确诊断是必要的。为此，我们将采用胸骨挫伤的临床前模型来促进对宫颈索中DTI变化的理解，作为损伤的标志。假设和特定目的：我们假设高颈脊髓的高级MRI是组织损伤和损伤严重程度的准确生物标志物，这是预后的。为了审查这一假设，我们将采用大鼠脊髓脊髓损伤的大鼠模型，并进行体内MRI，功能评估和组织病理学。我们将通过进行扩散的峰度成像（DKI）和定量T2（QT2）来测试我们的假设，以提高急性环境中的预后能力（AIM 1），将这些措施确立为损伤部位的组织损害的替代者（AIM 2）的替代制造商（AIM 2），并阐明了MRI造成的病理学机制的遥控器，而远距离造成了远程造成的损害。为了实现这些目标，使用体内DKI和QT2的多学科方法，定量组织病理学分析和功能评估将对非侵入性成像标记物及其生物学基础和功能意义之间的关系提供全面的理解。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，颈绳DTI的变化准确地反映了通过遗憾的白质量评估的损伤部位的损伤程度。最后，据称，除了轴突变性和脱髓鞘外，星形胶质细胞反应性是损伤的突出特征，与损伤远距离发生，并且与功能恢复的程度有关。总的来说，这些研究将建立并验证HCDTI为SCI的敏感生物标志物，并有可能改善预后，并将指导转化为人类SCI。