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技术，用于医学诊断。肝弹性成像已经成为肝纤维化无创分期的一种临床模式。相比之下，尽管磁共振弹性成像（MRE）在证明神经元粘弹性常数对疾病的高度敏感性方面取得了初步成功，但在脑成像中使用弹性成像仍然有限。该项目的目标是通过在小鼠模型中使用MRE来测试并最终建立粘弹性作为神经炎症和神经退行性过程的定量生物标志物。以下小鼠模型将被研究：(i)实验性自身免疫性脑炎（EAE）作为多发性硬化症诱导的神经炎症模型，（ii） 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）作为帕金森病中增强的成人神经发生和神经变性的公认模型，MRE结合广泛的组织学研究将使我们能够揭示和系统地分析神经组织粘弹性基质的疾病相关改变。特别是以下机制：(i)脱髓鞘，（ii）神经胶质的激活和激活模式的分布，（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，以及（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，拟议的项目对于人类MRE的验证和更深入的理解至关重要，这将在一个并行项目中进行研究。此外，小鼠的神经磁共振成像是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.