Collaborative Research: Multiple Scale Biomechanics of Tissue Damage in the White Matter of the Human Central Nervous System

运动中头部撞击或战争中爆炸效应造成的创伤性脑损伤（TBI）的长期后果现在被普遍认为是危险的。 即使是轻微的头部撞击也需要患者监测，尽管不完全知道持续多久。 为了照顾那些受伤不太明显的人，并衡量病人是否已经痊愈，需要新的脑成像方法。 这项研究旨在改善脑损伤的预测和监测。 白色物质的损失是脑组织损伤后的变化之一。头部撞击如何作为压力在大脑中分布尚不清楚，我们也不知道脑细胞对压力的耐受性。该研究项目将使用快速共聚焦显微镜和磁共振成像（MRI）技术来开发和验证可以预测细胞损伤的脑白色物质的多尺度力学模型。 该经验证的模型将用于使用全脑的撞击模型来估计脑中的轴突损伤。 该研究将用于本科生和研究生的教育。 PI在机械和航空航天工程领域建立了GirlsConnect俱乐部，以增加妇女在这一领域的参与和保留。该项目将侧重于确定当组织暴露于动态机械拉伸时，白色物质内单个轴突的损伤阈值。这项跨学科的研究建立在创新的实验方法，以了解轴突运动学和新颖的多尺度计算模型的合作团队介绍：（i）轴突水平的位移和亚故障轴突损伤后，临床相关的，动态加载的白色物质的分析;（ii）轴突和神经胶质基质相互作用的复合力学的计算结合，包括损伤，进入全球（宏观）响应的白色以下组织规模的负荷;（iii）定量预测应力集中在轴突水平的计算模型;和（iv）临床成像（MRI和磁共振弹性成像）和随后的组织病理学的整合以及机械特性与轴突损伤的相关性。多尺度模型将能够预测轴突微结构损伤和髓鞘变性引起的体积力学性能变化。预计该模型可以很容易地集成到先进的成像模式，以预测和监测脑损伤和疾病。该奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

The debilitating long-term consequences of traumatic brain injury (TBI) caused by head impacts in sports or blast effects in war are now generally recognized as dangerous. Even milder head impacts require patient monitoring, though for how long is not completely known. To care for people with less obvious injuries and to measure whether a patient has healed, new approaches to brain imaging are needed. This research is targeted at improving the prediction and monitoring of brain injuries. A loss of white matter is one of the changes in brain tissue after injury. How the head impact is distributed as stress in the brain is not known, nor do we know the tolerance of brain cells to stress. This research project will use fast confocal microscopy and Magnetic Resonance Imaging (MRI) techniques to develop and validate a multiscale mechanical model for brain white matter that can predict cell injury. This validated model will be used to estimate axonal injury in the brain using impact models of the whole brain. The research will be used in the education of undergraduate and graduate students. The PI instituted the GirlsConnect club in Mechanical and Aerospace Engineering to increase the participation and retention of women in this field.This project will focus on identifying the injury thresholds for individual axons within white matter when the tissue is exposed to dynamic, mechanical stretch. This interdisciplinary research builds on the innovative experimental approaches to understand axon kinematics and novel multi-scale computational models of the collaborative team to introduce: (i) Analysis of axon-level displacements and sub-failure axonal damage following clinically-relevant, dynamic loading of white matter; (ii) Computational incorporation of the composite mechanics of axon and glial matrix interaction, including damage, into the global (macro) response of the white matter following tissue-scale loading; (iii) Quantitative prediction of stress concentrations at the axon-level from the computational models; and (iv) Integration of clinical imaging (MRI and Magnetic Resonance Elastography) and subsequent histopathology and correlation of mechanical properties to axonal damage. The multi-scale model will enable the prediction of changes in bulk mechanical properties from damage to the axonal microstructure and from myelin degeneration. It is anticipated that this model can be easily integrated into advanced imaging modalities to predict and monitor brain injury and disease.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.