Micro-histological MRI of White Matter Cytoarchitecture in Alzheimers Disease

描述(申请人提供)：磁共振成像(MRI)已经成为实时对静态和时间敏感的生物事件进行软组织成像的强大工具 允许探索新的医疗技术。随着磁共振成像技术的进步，组织标本的显微成像已经成为一种手段，可以进一步提高我们对疾病过程的理解，推动对创新治疗策略的测试和验证。与阿尔茨海默病(AD)相关的生物学过程一直受到密切关注，因此，疾病治疗策略的确定仍然难以捉摸。在阿尔茨海默病中，磁共振成像技术的组织病理学基础及其与疾病过程的关联并不完全被理解。本研究的重点是利用磁共振成像来探讨阿尔茨海默病中与神经组织改变相关的MR松弛的潜在机制和组织病理学基础。有大量证据支持这一假设，即阿尔茨海默病不仅是一种皮质灰质(即神经元)疾病，而且是一种皮质和皮质下白质完整性疾病。最近的研究表明，AD大脑中存在白质变化，并在已知的形成β-淀粉样斑块的区域发现。神经发育过程中髓鞘形成较晚的区域被发现在疾病过程的早期就会形成β-淀粉样斑块，而较早形成髓鞘的区域在阿尔茨海默病进展中很大程度上是不会出现的。这一现象目前还不清楚，并框架了髓鞘参与AD的过程。在与疾病状态引起的微结构和超结构模式的改变有关的结构和解剖MRI指标的原因和解释方面，在成像领域内存在差距。研究表面上报道了MRI图像指标与阿尔茨海默病状态的关系，然而，MRI异常的确切解剖病理相关性仍不清楚。这导致了在没有直接了解图像对比度和细胞结构之间的关系的情况下，在临床解释疾病过程中使用结构MRI表现时的一个基本问题。这项研究的目的涉及与阿尔茨海默病病理相关的早期和晚期髓鞘皮质白质成分和完整性的显微磁共振和随后的组织学评估。阿尔茨海默氏症和对照组织切片将用先前建立的组织学方法以及各种组织学检查技术进行磁共振成像。其目的是从组织学、磁共振成像和显微镜下评估AD皮质组织中的白质，以支持这一假说，即皮质白质和相关微结构在AD过程中发生改变，可通过磁共振成像检查，并可用于早期诊断、确定和跟踪疾病进展，以支持疾病进展的生物标记物。

DESCRIPTION (provided by applicant): Magnetic resonance imaging (MRI) has emerged as a powerful tool for soft tissue imaging of static and time sensitive biological events in real time allowing the exploration of novel medical techniques. With the advancement of MRI technology the microimaging of tissue samples has become possible as a means to further enhance our understanding of disease processes and move forward testing and validation of innovative therapeutic strategies. The biological process associated with Alzheimer's disease (AD) is under constant scrutiny and as such the determination of disease therapeutic strategies has remained elusive. The histo-pathological basis of MR imaging techniques and their association to disease processes is not entirely understood in AD. This research focuses on the utilization of magnetic resonance imaging to pursue the underlying mechanism and histo-pathological basis of MR relaxation associated with neural tissue alterations in Alzheimer's disease. There is a body of evidence supporting the hypothesis that Alzheimer's disease is not only a cortical gray matter (i.e. neuronal) disease but also one of cortical and sub-cortical white matter integrity. Recent research has shown that white matter alterations are present in the AD brain and are found in regions known to form beta-amyloid plaques. Regions the myelinate later during neural development have been found to development beta-amyloid plaques early in the disease process while regions that myelinate earlier are largely spared until later in Alzheimer's progression. This phenomena is not currently understood and frameworks the involvement of myelin in the AD process. A gap exists within the imaging field in linking the cause and interpretation of structural and anatomical MRI metrics in relation to alterations in micro- and ultra-structural patterns due to disease state. Studies have ostensibly reported the relation of MRI image metrics to the Alzheimer's disease state, however the exact anatomic-pathologic correlates of MRI aberrations remains unclear. This results in a fundamental concern when using structural MRI findings in the clinical interpretation of disease processes without direct knowledge of the relationship between image contrast and cyto-architecture. The aims of this research involve the microscopic magnetic resonance and subsequent histological evaluation of early and late myelinating cortical white matter composition and integrity in relation to Alzheimer's disease pathology. Alzheimer's and control tissue sections will be MR imaged with previously established histological methods along with the utilization of various histological examination techniques. The objective being to histologically MR image and microscopically evaluate white matter in AD cortical tissue, in support of the hypothesis that cortical white matte and related microstructure is altered in the AD process, reviewable with MR imaging, and can be utilized in early diagnosis determination and tracking of disease progression in support of a biomarker of disease progression.