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

由运动中的头部撞击或战争中的爆炸效应引起的创伤性脑损伤（TBI）的长期衰弱后果现在普遍认为是危险的。即使是轻微的头部撞击也需要病人监测，尽管不完全清楚持续多久。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。本研究旨在提高对脑损伤的预测和监测。脑白质丢失是脑损伤后脑组织的变化之一。我们不知道头部的冲击是如何作为压力在大脑中分布的，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）技术来开发和验证脑白质的多尺度力学模型，该模型可以预测细胞损伤。该验证模型将用于使用全脑冲击模型来估计脑轴突损伤。本研究将用于本科生和研究生的教育。PI设立了机械和航空航天工程领域的GirlsConnect俱乐部，以增加妇女在这一领域的参与和保留。该项目将着重于确定当组织暴露于动态机械拉伸时，白质内单个轴突的损伤阈值。这项跨学科研究建立在理解轴突运动学的创新实验方法和协作团队的新型多尺度计算模型的基础上，介绍：(i)分析与临床相关的白质动态加载后轴突水平位移和亚失效轴突损伤；（ii）将包括损伤在内的轴突和胶质基质相互作用的复合力学计算纳入到组织尺度加载后白质的整体（宏观）反应中；（iii）利用计算模型定量预测轴突水平的应力集中；（iv）整合临床影像学（MRI和磁共振弹性成像）和随后的组织病理学以及机械性能与轴突损伤的相关性。多尺度模型将能够预测轴突微观结构损伤和髓鞘变性引起的总体力学性能变化。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。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.