Invivo imaging of mouse spinal cord axonal degeneration

描述（由申请人提供）：本项目的总体目标是利用磁共振成像（MRI）研究小鼠脊髓轴突变性模型。在中枢神经系统（CNS）中，脊髓是连接周围神经系统和大脑的主要通道。由于损伤、中毒或神经系统疾病引起的脊髓损伤常引起轴突变性。多发性硬化症（MS）就是一个例子。多发性硬化症的特点是脱髓鞘和轴突损伤，导致轴突变性。在MS患者中，轴突变性在神经功能障碍的发展中起着重要作用，并已被确定为不可逆神经功能障碍的主要决定因素。为了了解多发性硬化症和脊髓损伤中轴突变性的确切机制，人们建立了几种小动物模型，如实验性过敏性脑脊髓炎（EAE）模型。能够无创监测轴突变性状态的技术将为轴突的发病机制、治疗效果和再生提供重要的时空信息。目前，对小鼠轴突变性的无创监测难以实现。小鼠脊髓的微型尺寸（直径约2毫米）需要很高的空间分辨率。在这项提议中，我们将开发体内高分辨率MRI技术，用于定量测量小鼠脊髓组织T2（横向松弛时间），平均表观扩散常数（ADC）和扩散各向异性。然后，这些技术将用于表征L4L5背根切开术小鼠的轴突变性。结果将与体外磁共振测量和组织病理学相关联。

DESCRIPTION (provided by applicant): The overall goal of this project is to study spinal cord axonal degeneration in a mouse model using magnetic resonance imaging (MRI). In the central nervous system (CNS), the spinal cord acts as the major pathway between the peripheral nervous system and the brain. Damages to the spinal cord due to injuries, toxic exposure, or neurological diseases often cause axonal degeneration. One example is Multiple Sclerosis (MS). MS is characterized by demyelination and axonal damage, which leads to axonal degeneration. In MS patients, axonal degeneration plays an important role in the development of neurological disability and has been identified as the major determinant of irreversible neurological disability. To understand the precise mechanisms of axonal degeneration in MS and spinal cord injuries, several small animal models have been developed, such as the experimental allergic encephalomyelitis (EAE) model. Techniques that can non- invasively monitor the state of axonal degeneration will provide important information on the spatial and temporal profiles of pathogenesis, treatment efficacy, and axonal regeneration. Currently, non-invasive monitoring of axonal degeneration is difficult to achieve in the mouse. The miniature size of the mouse spinal cord (1approximately 2 mm in diameter) requires high spatial resolution. In this proposal, we will develop in vivo high resolution MRI techniques for quantitative measurement of tissue T2 (transverse relaxation time), averaged apparent diffusion constant (ADC,) and diffusion anisotropy in the mouse spinal cord. These techniques will then be used to characterize axonal degeneration in mice that undergo L4L5 dorsal radiculotomy. The results will then be correlated with ex vivo MR measurements and histopathology.