Evaluation of developing lesions with a combined approach of Magnetic Resonance Imaging, Magnetic Resonance Elastography and histopathology in an animal model of multiple sclerosis.
结合磁共振成像、磁共振弹性成像和组织病理学在多发性硬化症动物模型中评估病变进展情况。
基本信息
- 批准号:317305913
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:德国
- 项目类别:Research Fellowships
- 财政年份:2016
- 资助国家:德国
- 起止时间:2015-12-31 至 2016-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Multiple Sclerosis (MS) is the most common neuroinflammatory disease. It leads to demyelination, axonal and neuronal damage in the central nervous system resulting in considerable impairment of those affected. MS is an immune-mediated disorder in genetically susceptible individuals. However, cause and pathogenesis are still unknown. Magnetic Resonance Imaging (MRI) has emerged as most important paraclinical tool to diagnose and monitor MS. However, conventional MRI-parameters lack specificity and correlate only poorly with the clinical course. Additionally, they hardly allow conclusions to be drawn with regard to the underlying pathology and the prognostic value is limited. Hence, novel in vivo parameters are needed to improve this situation.The proposed project focuses on the detection of inflammatory foci in the brain of MS patients in a very early stage. The experimental autoimmune encephalitis (EAE) mouse model will be used to test whether early neuroinflammatory changes can be depicted. Conventional MRI will be combined with a special arterial spin labeling (ASL) technique allowing for the quantification of vessel permeability and with Magnetic Resonance Elastography (MRE). MRE provides quantitative information on the biomechanical properties of a tissue non-invasively and in vivo. These properties are acquired by analyzing the propagation of low-frequency shear waves, which are mechanically elicited in the organ of interest. Finally, imaging parameters will be correlated to histopathological analyses focusing on inflammation, myelin and the extracellular matrix.Lesion development in MS and EAE respectively comprises the influx of autoreactive T-cells in the brain, recruitment and activation of further immune cells leading to demyelination and damage of axons and neurons. These processes interfere with the normal geometrical network of the brain parenchyma, which renders them mechanically detectable with MRE.During acute inflammation, some mediators are released leading to a disruption of the blood brain barrier (BBB). This can be investigated with a novel ASL method. It renders information on the capillary transfer time, a parameter reflecting changes in the integrity of the BBB as it is linked to capillary function.In order to facilitate influx of immune cells and to make the site of lesion development predictable, the BBB will be gradually opened in a predefined area using focused ultrasound. In summary, the project combines the evaluation of BBB integrity and the assessment of biomechanical properties in the EAE-model of MS to potentially find a biomarker able to predict the development of lesions. Such a biomarker has the potential to significantly improve the management of MS-patients. The non-invasive identification of early inflammatory activity could firstly facilitate the diagnosis of MS, secondly improve decision-making when a treatment should be initiated or modified and thirdly could help to predict the disease course.
多发性硬化(MS)是最常见的神经炎性疾病。它导致脱髓鞘,中枢神经系统的轴突和神经元损伤,导致受影响的人受到相当大的损害。多发性硬化症是一种遗传易感个体的免疫介导的疾病。然而,病因和发病机制尚不清楚。磁共振成像(MRI)已成为诊断和监测ms最重要的临床辅助工具,然而,传统的MRI参数缺乏特异性,与临床病程的相关性很差。此外,它们很难得出关于潜在病理和预后价值有限的结论。因此,需要新的体内参数来改善这种情况。拟建项目的重点是在非常早期的阶段检测MS患者的大脑炎症灶。实验性自身免疫性脑炎(EAE)小鼠模型将用于测试是否可以描述早期神经炎症变化。传统的MRI将结合一种特殊的动脉自旋标记(ASL)技术,允许血管渗透率的量化,并与磁共振弹性成像(MRE)相结合。MRE提供了非侵入性和体内组织生物力学特性的定量信息。这些特性是通过分析低频剪切波的传播而得到的,这些剪切波是机械地在感兴趣的器官中引起的。最后,成像参数将与聚焦于炎症、髓磷脂和细胞外基质的组织病理学分析相关。MS和EAE的病变发展分别包括自身反应性t细胞涌入大脑,募集和激活进一步的免疫细胞,导致脱髓鞘和轴突和神经元损伤。这些过程干扰了脑实质的正常几何网络,这使得它们在机械上可以被磁共振检测到。在急性炎症期间,一些介质被释放,导致血脑屏障(BBB)的破坏。这可以用一种新的ASL方法来研究。它提供了有关毛细血管转移时间的信息,这是一个反映血脑屏障完整性变化的参数,因为它与毛细血管功能有关。为了促进免疫细胞的涌入,并使病变发展的位置可预测,将使用聚焦超声在预定区域逐渐打开血脑屏障。综上所述,该项目结合了MS eae模型中BBB完整性评估和生物力学特性评估,以潜在地找到能够预测病变发展的生物标志物。这种生物标志物有可能显著改善ms患者的管理。早期炎症活动的无创识别首先有助于MS的诊断,其次可以改善何时开始或修改治疗的决策,第三可以帮助预测病程。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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