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

合作研究：人类中枢神经系统白质组织损伤的多尺度生物力学

基本信息

批准号：
1763005
负责人：
Assimina Pelegri
金额：
$ 33.28万
依托单位：
Rutgers University New Brunswick
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2023-06-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1763005&HistoricalAwards=false
关键词：
Collaborative Research Multiple Scale Biomechanics

项目摘要

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.

体育运动中的头部撞击或战争中的爆炸效应造成的创伤性脑损伤 (TBI) 造成的长期衰弱后果现在普遍被认为是危险的。即使是较轻微的头部撞击也需要对患者进行监测，但具体持续多长时间尚不完全清楚。为了照顾损伤不太明显的人并测量患者是否已经痊愈，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。白质损失是受伤后脑组织的变化之一。目前尚不清楚头部冲击如何以压力形式分布在大脑中，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质多尺度力学模型。该经过验证的模型将用于利用整个大脑的影响模型来估计大脑中的轴突损伤。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，以提高女性在该领域的参与度和保留率。该项目将重点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合作团队的新颖的多尺度计算模型的基础上，介绍：（i）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的分析； (ii) 将轴突和神经胶质基质相互作用的复合力学（包括损伤）计算纳入组织尺度负载后白质的整体（宏观）响应中； (iii) 根据计算模型定量预测轴突水平的应力集中； (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由于轴突微观结构损伤和髓磷脂变性而导致的整体机械性能的变化。预计该模型可以轻松集成到先进的成像模式中，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，被认为值得支持。

项目成果

期刊论文数量（13）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Oligodendrocyte Tethering Effect on Hyperelastic 3D Response of Injured Axons in Brain White Matter

少突胶质细胞束缚对脑白质损伤轴突超弹性 3D 反应的影响

DOI：
10.1115/imece2021-73376
发表时间：
2021
期刊：
ASME International Mechanical Engineering Congress and Exposition (IMECE
影响因子：
0
作者：
Agarwal, Mohit;Pasupathy, Parameshwaran;De Simone, Robert;Pelegri, Assimina A.
通讯作者：
Pelegri, Assimina A.

On the Transversely Isotropic, Hyperelastic Response of Central Nervous System White Matter Using a Hybrid Approach

使用混合方法研究中枢神经系统白质的横向各向同性超弹性响应