Novel Diffusion MRI Encoding in Rat Spinal Cord Injury Assessment

项目摘要 脊髓损伤(SCI)是一种衰弱的疾病，对急性脊髓损伤的评估具有很大的局限性。 严重，使及时和有效的治疗策略复杂化。扩散张量成像(DTI)是一种 检测显微组织的磁共振成像(MRI)研究技术前景看好 脊髓损伤，但需要较长的扫描时间，对重要的预后缺乏特异性 细胞损伤的标记物，降低了其临床实用性。这个项目的目标是应用一种新的 弥散磁共振成像技术克服了这些局限性，提高了脊髓损伤的诊断和预后。 这种称为双扩散编码(DDE)的技术是专门为评估轴突而量身定做的 脊髓的完整性，已被证明是预测功能结果的最佳指标 损伤后，通过降低其对水肿和其他扰乱扩散的过程的敏感性 测量。初步数据表明，DDE测量能够更敏感地 与DTI相比，损伤的获取时间大大减少。此外，自动化的DDE 分析只需要最少的数据后处理，并提供了比 通常与DTI一起使用的耗时的手动感兴趣区域绘制。因此，DDE 这项技术提供了比DTI更多的好处，增加了其潜在临床应用的可行性 SCI的评价。该项目的目的是证明扩散变化的细胞基础。 用DDE进行测量，并将其作为长期功能恢复的预后指标。这 该方法将使用大鼠脊髓挫伤模型进行评估，该模型由体重引起的严重程度分级 掉落伤痕。MRI测量结果与金标准组织学定量结果的比较 证明DDE参数与轴突损伤之间有很强的相关性(目标1)。这个 这种新方法的预后能力也将在急性DDE的能力中进行测试 用于预测损伤后慢性神经系统功能的测量(目标2)。结果是 这些研究将影响SCI评估的临床前和临床应用。 对轴突损伤的敏感性将更好地为干预、治疗和康复策略提供信息。 该项目的翻译性质，加上对科学基本原理的培训 调查，将推动我继续取得成功，成为一名独立的长期目标 内科科学家。

Project Summary Spinal cord injury (SCI) is a debilitating condition with significant limitations for acute evaluation of severity, complicating prompt and effective treatment strategies. Diffusion Tensor Imaging (DTI) is a promising magnetic resonance imaging (MRI) research technique for detecting microscopic tissue injury in SCI, but requires long scan durations and lacks specificity for the important prognostic marker of cellular damage, reducing its clinical usefulness. The goal of this project is to apply a novel diffusion MRI technique to overcome these limitations and improve diagnosis and prognosis of SCI. This technique, termed double diffusion encoding (DDE), was specifically tailored to evaluate axonal integrity in the spinal cord, which has been shown to be the best predictor of functional outcome following injury, by reducing its sensitivity to edema and other processes that confound diffusion measurements. Preliminary data demonstrate that DDE measurements enable greater sensitivity to injury than DTI with a substantially reduced acquisition time. Furthermore, the automated DDE analysis requires minimal data post-processing and provides an important objective benefit over the time-consuming manual region of interest drawing commonly used with DTI. Thus, the DDE technique provides multiple benefits over DTI that increase its feasibility for potential clinical evaluation of SCI. The aims of the project are to demonstrate the cellular basis for diffusion changes measured with DDE and its use as a prognostic indicator for long-term functional recovery. This method will be evaluated using a rat contusion model of SCI with graded severities induced by weight drop injuries. Comparison of MRI measurements to gold-standard histological quantification will demonstrate the strong association between DDE parameters and axonal injury (Aim 1). The prognostic capabilities of this new method will also be tested in the ability of acute DDE measurements to predict chronic nervous system function following injury (Aim 2). The results of these studies will impact both preclinical and clinical applications of SCI evaluation where improved sensitivity to axonal damage will better inform intervention, treatment, and rehabilitation strategies. The translational nature of the project, coupled with training in fundamental principles of scientific investigation, will promote continued success in my long-term goal to become an independent physician scientist.