Evaluation of Spinal Cord White Matter Injury Using DTI

描述（由申请人提供）：脊髓损伤（SCI）是最具破坏性的创伤事件之一。 超过200，000名美国人因车祸、运动损伤和其他创伤而患有SCI。 由于脊髓白质病变通常导致SCI患者瘫痪和感觉丧失，因此开发非侵入性方式以提供SCI潜在病理学的详细评估至关重要。 此外，随着新疗法的开发，重要的是具有白色物质损伤的指标作为损伤程度和治疗反应的替代标记。 本文提出的弥散张量成像（DTI）的分析使用可以提供一个这样的指标，并与我们开发DTI技术，以帮助改善SCI患者的生活质量的更广泛的目标是一致的。 弥散张量成像技术已广泛应用于中枢神经系统（CNS）的组织形态学和病理学分析。 近年来，DTI在脊髓损伤中用于评估损伤的严重程度和进展的使用也有所增加。 然而，DTI的常规使用没有解决非侵入性地检测和区分CNS白色物质损伤的潜在病理的更迫切的需要，即，轴突损伤、脱髓鞘和炎症。在这项研究中，我们建议使用目前可用的DTI技术，以建立一个直接的联系之间的定向扩散率和潜在的白色物质的病理在SCI。具体来说，我们将使用具有高度特异性、明确病理学的SCI小鼠模型来量化主要与以下相关的DTI参数：髓鞘变性（Aim 1）、轴突损伤后脱髓鞘（Aim 2）以及伴有/不伴有轴突和髓鞘损伤的炎症（Aim 3）。预期髓鞘降解将先于具有轴突和髓鞘损伤的炎症的目标3中的轴突损伤，与我们预期轴突损伤随后脱髓鞘的目标2相反。将通过组织学分析（包括髓鞘染色、轴突染色和透射电子显微镜（EM））验证体内DTI结果。

DESCRIPTION (provided by applicant): Spinal cord injury (SCI) is one of the most devastating traumatic events. More than 200,000 Americans are living with SCI resulting from automobile accidents, sports injuries, and other trauma. Since white-matter lesions of the spinal cord usually result in paralysis and sensory loss in SCI patients, it is crucial that non-invasive modalities be developed to provide a detailed assessment of the underlying pathology of SCI. Further, as new therapies are developed, it is important to have indicators of white matter injury as surrogate markers for degree of damage and therapeutic response. The analytical use of diffusion tensor imaging (DTI) proposed herein may provide one such indicator and is consistent with our broader goal of developing DTI technology to help improve the quality of life of SCI patients. DTI has been widely applied in central nervous systems (CNS), providing detailed analysis of tissue morphology and pathology. Increased use of DTI in spinal cord injury for assessment of severity and progression of the damage has also been seen in recent years. However, conventional use of DTI has not addressed the more pressing need to non-invasively detect and differentiate underlying pathologies of the CNS white matter injury, i.e., axonal injury, demyelination, and inflammation. In this study, we propose to use the currently available DTI technology to establish a direct link between directional diffusivities and underlying white matter pathologies during SCI. Specifically, we will use mouse models of SCI with highly-specific, well-defined pathology to quantify DTI parameters relating primarily: myelin degeneration (Aim 1), axonal injury followed by demyelination (Aim 2), and inflammation with/without axonal and myelin injury (Aim 3). It is expected that myelin degradation will precede axonal injury in Aim 3 of inflammation with axonal and myelin injury, in contrast to Aim 2 in which we expect axonal injury followed by demyelination. In vivo DTI findings will be validated by histological analysis including myelin staining, axonal staining, and transmission electron microscopy (EM).