Advanced MRI of Spinal Cord Injury

脊髓损伤的高级 MRI

• 批准号: 10356042
• 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 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10356042
• 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; T2 weighted imaging; Techniques; Technology; Testing; Therapeutic Intervention; Time; Translating; Trauma; United States Department of Veterans Affairs; Veterans; Visualization; acute care; axon injury; base; clinical prognostic; 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 method; prognostic value; prognostication; 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.

基本原理和初步数据：我们将对人类脊髓损伤 (SCI) 进行研究以验证 MRI 使用新型扩散 MRI 技术开发损伤严重程度的生物标志物和预后预测 专门用于检测脊髓中的轴突损伤。预测 SCI 的结果一直是一个长期目标 更好的临床管理并帮助开发和测试疗法。传统神经科 检查并不能准确预测结果，传统 MRI（包括 T2 加权成像） 虽然对诊断有用，但不能准确预测恢复程度。扩散张量成像 (DTI) 已显示出作为 SCI 预后成像生物标志物的前景，但其临床应用受到以下因素的阻碍 技术挑战和潜在病理学的非特异性。我们在大鼠 SCI 模型中进行的临床前研究 已证明双扩散编码 (DDE) MRI 对急性轴突损伤敏感并可预测 结果的准确性优于 DTI 或传统功能评分。同样，最近的事态发展 我们的合作小组已经证明了在金属手术附近采用扩散对比的能力 硬件，这很容易出现伪影。虽然前景光明，但同时验证这些技术 提高对比度和质量对于推进技术并确保其在人类受试者中的实用性至关重要 临床环境。该项目将转化这些技术以增进对 DTI 变化的理解 在脐带中作为受伤标记。我们的假设是 1) 在急性环境中，急性轴突的 DDE 估计 损伤将预测长期功能结果，2) 在慢性环境中，DDE 估计永久功能 轴突损失将与现有的功能结果相关。预计DDE的表现将优于DTI， 传统 MRI 或 SCI 中的功能神经学检查。为了验证这个假设，我们将进行体内 MRI 以及创伤性脊髓损伤后急性期的功能评估。在目标 1 中，我们将检查 DDE 通过后续功能评估预测后期神经功能恢复的预后能力。瞄准 2，我们将详细介绍通过 DDE 测量的轴突损失（保留）与永久性神经功能之间的联系 SCI之后。这些研究旨在建立和验证 DDE 作为损伤严重程度和结果的替代指标 并与现有的临床标准和既定的SCI MRI指标进行比较。我们假设基于 根据强有力的临床前结果，使用 DDE 检测微结构损伤将更准确地反映 与 MRI 技术相比，神经损伤程度对潜在病理非特异性。的潜力 DDE 突出了临床翻译的特点，即只需几分钟即可快速获取数据，并且需要最少的时间 用于量化的后处理或事后分析。此外，DDE 可以实现程度的可视化 个体受试者的损伤，使其在 SCI 患者的临床治疗中具有广阔的前景。总的来说，这些 研究将建立并验证 DDE 作为 SCI 的生物标志物，有可能改善预后 人类SCI。