Advanced MRI of Spinal Cord Injury

脊髓损伤的高级 MRI

• 批准号: 9900574
• 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: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9900574
• 关键词: Acute; Adoption; Atrophic; Axon; Biological Markers; Caring; Cervical spinal cord injury; Cervical spinal cord structure; Chronic; Clinical; Clinical Management; Complement; Cross-Sectional Studies; Data; Detection; Development; Diagnosis; Diagnostic Procedure; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Distant; Edema; Ensure; Goals; Hour; Human; Image; Imaging Techniques; Impairment; Individual; Injury; Linear Regressions; Link; Longitudinal Studies; Magnetic Resonance Imaging; Measurement; Measures; Metals; Methods; Modeling; Monitor; Morphologic artifacts; Motor; Nervous System Physiology; Nervous System Trauma; Neurologic; Neurologic Examination; Neurological outcome; Operative Surgical Procedures; Outcome; Pathologic; Pathology; Patient Outcomes Assessments; Patients; Phase; Pre-Clinical Model; Prognostic Marker; Quality of life; Rattus; Recovery; Reporting; Scientist; Sensory; Severities; Signal Transduction; Site; Specificity; Spinal Cord; Spinal cord injury; Spinal cord injury patients; Structure; T2 weighted imaging; Techniques; Technology; Testing; Therapeutic Intervention; Time; Translating; Trauma; Veterans; Visualization; acute care; axon injury; base; clinical translation; contrast imaging; follow-up; functional outcomes; functional status; human subject; imaging biomarker; imaging modality; improved; in vivo; injured; magnetic resonance imaging biomarker; neurological recovery; novel; novel strategies; outcome prediction; pre-clinical; preclinical study; prognostic; prognostic value; spinal cord imaging; success; technology validation; therapy design; tool; translation to humans; translational study

Rationale and Preliminary Data: We will conduct a study of human spinal cord injury (SCI) to validate MRI biomarkers of injury severity and prognostication of outcome using a novel diffusion MRI technique developed specifically to detect axonal injury in the spinal cord. Predicting outcome from SCI has been a longstanding goal for better clinical management and aiding in the development and testing of therapies. Traditional neurological examination is not an accurate predictor of outcome, and conventional MRI, including T2-weighted imaging, while useful for diagnosis, does not accurately predict the degree of recovery. Diffusion tensor imaging (DTI) has shown promise as a prognostic imaging biomarker in SCI, but its clinical adoption has been hindered by technical challenges and non-specificity to the underlying pathology. Our preclinical studies in a rat SCI model have demonstrated that double diffusion encoding (DDE) MRI is sensitive to acute axonal injury and predicts outcome with accuracy better than either DTI or traditional functional scoring. Likewise, recent developments by our collaborative group have demonstrated the ability to employ diffusion contrast adjacent to metal surgical hardware, which is prone to artifacts. While promising, validation of these technologies to simultaneously improve contrast and quality is critical to advance the technology and ensure its utility in human subjects and clinical settings. This project will translate these techniques to advance the understanding of the DTI changes in the cord as markers of injury. Our hypotheses are 1) in the acute setting, DDE estimates of acute axonal injury will predict long-term functional outcomes, and 2) in the chronic setting, DDE estimates of permanent axonal loss will correlate with existing functional outcomes. It is predicted that DDE will outperform DTI, conventional MRI, or functional neurological exams in SCI. To test this hypothesis, we will perform in vivo MRI and functional assessments in the acute phase after traumatic spinal cord injury. In Aim 1, we will examine the prognostic ability of DDE to predict later neurological recovery using follow-up functional assessments. In Aim 2, we will detail the link between axonal loss (sparing) as measured by DDE and permanent neurological function after SCI. These studies seek to establish and validate DDE as a surrogate maker of injury severity and outcome and compare it with existing clinical standards and established MRI indicators of SCI. We hypothesize based on strong preclinical results that detection of microstructural injury using DDE will more accurately reflect the degree of neurological impairment than MRI techniques non-specific to underlying pathology. The potential for clinical translation is highlighted by DDE being a rapid acquisition of only a few minutes and requires minimal post-processing or post-hoc analysis for quantification. Moreover, DDE enables visualization of the degree of injury in individual subjects, making it promising for clinical management of SCI patients. Collectively, these studies will establish and validate DDE as a biomarker of SCI with the potential to improve prognostication in human SCI.

理由和初步数据：我们将对人脊髓损伤（SCI）进行研究以验证MRI 使用新型扩散MRI技术开发了损伤严重程度和预后的生物标志物 专门检测脊髓中的轴突损伤。从SCI预测结果一直是一个长期目标 为了更好地临床管理并有助于疗法的开发和测试。传统神经系统 考试不是结果的准确预测指标和常规MRI，包括T2加权成像， 虽然可用于诊断，但不能准确预测恢复程度。扩散张量成像（DTI） 在SCI中表现出了作为预后成像生物标志物的承诺，但其临床采用受到了阻碍 对基本病理的技术挑战和非特异性。我们在大鼠SCI模型中的临床前研究 已经证明了双扩散编码（DDE）MRI对急性轴突损伤敏感，并预测 与DTI或传统功能评分更好的结果。同样，最近的发展 由我们的协作小组证明了具有与金属手术相邻的扩散对比的能力 硬件，容易产生工件。在有希望的同时，对这些技术的验证同时验证 改善对比度和质量对于推进技术并确保其在人类受试者中的效用至关重要 临床环境。该项目将翻译这些技术，以提高对DTI变化的理解 在电线中作为伤害的标记。我们的假设是1）在急性环境中，DDE急性轴突的估计值 伤害将预测长期功能结果，而2）在慢性环境中，DDE估计是永久性的 轴突损失将与现有的功能结果相关。据预测，DDE将胜过DTI， 常规MRI或SCI中的功能性神经检查。为了检验该假设，我们将在体内执行MRI 创伤性脊髓损伤后急性期的功能评估。在AIM 1中，我们将检查 DDE使用随访功能评估预测后来的神经恢复的预后能力。目标 2，我们将详细介绍DDE测量的轴突丢失（保留）和永久性神经功能 科幻之后。这些研究旨在建立和验证DDE为损伤严重性和结果的代替代人 并将其与现有的临床标准进行比较，并确定了SCI的MRI指标。我们假设基于 关于强烈的临床前结果，使用DDE检测微结构损伤将更准确地反映 神经系统损伤程度比MRI技术对基本病理学的非特异性障碍程度。潜力 DDE仅需几分钟就可以突出显示临床翻译，并且需要最少 用于定量的后处理或事后分析。此外，DDE可以可视化 单个受试者的伤害，使其对SCI患者的临床管理有希望。总的来说，这些 研究将建立并验证DDE作为SCI的生物标志物，并有可能改善预后。 人科学。