Evaluation of Spinal Cord White Matter Injury Using DTI

描述（申请人提供）：脊髓损伤（SCI）是最具破坏性的创伤性事件之一。超过20万美国人因车祸、运动损伤和其他创伤而患有脊髓损伤。由于脊髓白质病变通常会导致脊髓损伤患者瘫痪和感觉丧失，因此开发非侵入性模式以提供脊髓损伤潜在病理的详细评估至关重要。此外，随着新疗法的发展，将白质损伤指标作为损伤程度和治疗反应的替代标记物是很重要的。本文提出的弥散张量成像（diffusion tensor imaging， DTI）的分析使用可能提供了这样一个指标，并且与我们开发DTI技术以帮助改善SCI患者生活质量的更广泛目标是一致的。DTI在中枢神经系统（CNS）中得到了广泛的应用，提供了详细的组织形态学和病理学分析。近年来，越来越多地使用DTI来评估脊髓损伤的严重程度和损伤的进展。然而，传统的DTI并没有解决更迫切的需要，即无创检测和区分中枢神经系统白质损伤的潜在病理，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技术来建立定向扩散率与脊髓损伤期间潜在白质病理之间的直接联系。具体来说，我们将使用具有高度特异性、明确病理的脊髓损伤小鼠模型来量化DTI参数，这些参数主要涉及：髓鞘变性（Aim 1）、轴突损伤后脱髓鞘（Aim 2）、炎症伴/不伴轴突和髓鞘损伤（Aim 3）。我们预计，在轴突和髓鞘损伤的炎症的Aim 3中，髓鞘降解将先于轴突损伤，而在Aim 2中，我们预计轴突损伤之后是脱髓鞘。体内DTI的发现将通过组织学分析进行验证，包括髓磷脂染色、轴突染色和透射电镜（EM）。

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).