Neuro MRE (II): Correlation of histology and changes in viscoelastic properties of the brain in animal models

弹性成像是一种基于图像的生物软组织力学特性检测方法，用于医学诊断。肝脏弹性成像已经成为肝纤维化无创分期的一种成熟的临床模式。与此相反，使用脑成像的弹性成像仍然是有限的，尽管初步成功的磁共振弹性成像（MRE）在证明神经元的粘弹性常数的疾病的高灵敏度，拟议项目的目标是测试，并最终建立粘弹性作为定量生物标志物的神经炎症和神经退行性疾病的过程中使用MRE在小鼠模型。将研究以下小鼠模型：（i）实验性自身免疫性脑炎（EAE）作为多发性硬化诱导的神经炎症模型，和（ii）1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）作为帕金森病MRE中增强的成人神经发生和神经变性的公认模型，结合广泛的组织学研究，将使我们能够揭示和系统地分析疾病-神经组织的粘弹性基质的相关改变，特别是关于以下机制：（i）脱髓鞘，（ii）神经胶质活化和活化模式的分布，（iii）由于炎症机制如淋巴细胞浸润或内皮改变引起的细胞外基质的变化，和（iv）神经元的增殖、分化和整合到组织基质中。通过解决这些问题，拟议项目对于验证和更深入地了解人类的地雷危险教育至关重要，这将在一个平行项目中进行调查。此外，小鼠中的神经MRE作为弹性成像作为结构敏感成像方式的任何其他应用的基础。

Elastography is the image-based detection of the mechanical properties of biological soft tissues for medical diagnosis. Elastography of the liver has already become an established clinical modality for the noninvasive staging of hepatic fibrosis. In contrast, the use of elastography for brain imaging is still limited despite initial success of magnetic resonance elastography (MRE) in demonstrating the high sensitivity of neuronal viscoelastic constants to disease.The goal of the proposed project is to test and ultimately establish viscoelasticity as a quantitative biomarker for neuroinflammatory and neurodegenerative processes by using MRE in mouse models. The following mouse models will be investigated: (i) Experimental autoimmune encephalitis(EAE) as a model of neuroinflammation induced by multiple sclerosis, and (ii) 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) as an accepted model for enhanced adult neurogenesis and neurodegeneration in Parkinson's disease MRE combined with extensive histological investigations will enable us to reveal and systematically analyze disease-related alterations of the viscoelastic matrix of neural tissue, specifically with regard to the following mechanisms: (i) demyelination, (ii) glial activation and distribution of activation patterns, (iii) changes in the extracellular matrix due to inflammatory mechanisms such as lymphocytic infiltration or endothelial alterations, and (iv) proliferation, differentiation, and integration of neurons into the tissue matrix. By addressing these issues, the proposed project is pivotal for the validation and deeper understanding of MRE in humans, which will be investigated in a parallel project. Moreover, Neuro MRE in the mouse serves as the underpinning for any other application of elastography as a structure-sensitive imaging modality.