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使用磁共振成像（MRI）在小鼠模型中研究脊髓轴突变性。在中枢神经系统（CNS）中，脊髓充当周围神经系统和大脑之间的主要通路。由于损伤、毒性暴露或神经系统疾病对脊髓的损伤通常会导致轴突变性。一个例子是多发性硬化症（MS）。MS的特征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重要作用，并且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MS和脊髓损伤中轴突变性的确切机制，已经开发了几种小动物模型，例如实验性变态反应性脑脊髓炎（EAE）模型。能够非侵入性地监测轴突变性状态的技术将提供关于发病机制、治疗功效和轴突再生的空间和时间概况的重要信息。目前，在小鼠中难以实现轴突变性的非侵入性监测。小鼠脊髓的微小尺寸（直径约2 mm）需要高的空间分辨率。在这个建议中，我们将开发在体内的高分辨率MRI技术定量测量组织T2（横向弛豫时间），平均表观扩散常数（ADC）和扩散各向异性在小鼠脊髓。然后，这些技术将用于表征经历L4L5背侧神经根切断术的小鼠中的轴突变性。然后将结果与离体MR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.