Multi-Scale Modeling of Central Nervous System White Matter

本研究的主要目的是开发一种多尺度建模方法的基础上，有代表性的体积元素，使中枢神经系统（CNS）的白色物质，特别是脑和脊髓创伤的准确描述和有限元分析。要做到这一点的车辆是一个综合的多学科分析，计算和实验方法，包括几个同样重要的步骤。该项目的基本假设是，在脊髓创伤期间，轴突纤维既不牢固地束缚也不完全与胶质基质解偶联;事实上，随着拉伸的增加，它们变得更加束缚。为此，微观结构的运动学，忽略了目前的研究，需要纳入准确地表示和建模的白色物质的大脑和脊髓。在这个项目的过程中，我们将开发一种新的材料模型的中枢神经系统白色的问题，将捕捉微观尺度的行为轴突在宏观尺度的连续分析。该模型的开发将通过新的原位实验进行指导和测试。 建议的工作的主要智力价值在于计算纳入的微观结构的轴突和神经胶质细胞的功能和属性的CNS白色mater的全球（宏观）的反应，并在原位实验相关性和验证的模拟数据的各种负载的情况。这项研究的结果将引领轴突损伤耐受标准的发展，这是至关重要的，因为轴突损伤是TBI和SCI后功能丧失的近端原因。它还将有助于设计新的体内和体外模型，目标是基于计算机预测在特定模式和位置诱导损伤。社会影响在于，完成后，CNS白色模型将能够集成到SCI和TBI的分析中，具有更复杂的负载条件，以预测单轴突水平的损伤。这是中枢神经系统生物力学建模的一个突破，可以极大地促进诊断，最终导致改善损伤第一反应和治疗的手段和措施。该项目在基础研究和知识传播方面的影响是显而易见的，因为这个多学科项目带来了材料科学，生物工程，控制和高科技计算技术的任务，以开发最先进的组织诊断模型，具有独特的定量测量能力，并以数学方式对其进行全面描述。教育的影响将是显着的，我们的研究生不仅在科学和工程领域，而且在指导和推广，因为他们是我们的社区努力通过罗格斯大学未来学者计划的一个组成部分。积极招收少数民族和弱势群体的研究生和本科生。这些举措为这些学生提供了独特的机会，这将激发他们对工程教育和培训的兴趣，并有助于塑造我们科学和工程界未来的领导者。最后，为了支持成果传播和推广，主要参与者获得了参加CMMI两年一度的受赠者会议的资金。

The primary objective of this research is to develop a mutli-scale modeling approach based on representative volume elements to enable the accurate depiction and finite element analysis of central nervous system (CNS) white matter, in particular of brain and spinal cord trauma. The vehicle to do this is an integrated multi-disciplinary analytical, computational and experimental methodology consisting of several equally important steps. The underlying hypothesis for the project is that axon fibers are neither firmly tethered nor completely uncoupled to the glial matrix during spinal cord trauma; in fact, they become more tethered with increasing stretch. To this end, microstructural kinematics, omitted by current studies, need to be incorporated to accurately represent and model the white matter of the brain and spinal cord. During the course of this project, we will develop a novel material model for CNS white matter that will capture the micro-scale behavior of axons in a macro-scale continuum analysis. The development of this model will be guided and tested by novel in situ experiments. The major intellectual merit of the proposed work lies upon the computational incorporation of the microstructural axon and glial features and properties into the global (macro) response of the CNS white mater, and the in situ experimental correlation and validation of the simulation data for a variety of loading scenarios. Results from this research will spearhead the development of axon damage tolerance criteria, which is of paramount importance since injury to axons is the proximal cause for loss of function following TBI and SCI. It will also assist in designing new in vivo and in vitro models with the goal of inducing injury in specific patterns and locations based on in silico predictions.The societal impact lies in that, upon completion, the CNS white mater model will be able to be integrated into analyses of SCI and TBI with more complex loading conditions to predict injury at the single axon level. This is a breakthrough in the CNS biomechanical modeling, which can greatly facilitate diagnostics that can ultimately lead to improved means and measures of injury first response and treatment. The impact of this project in terms of basic research and the spread of knowledge is evident since this multidisciplinary program brings in tasks from materials science, bioengineering, controls, and hi-tech computational techniques, to develop a state of the art tissue diagnostic model, with unique quantitative measuring capabilities and that is described mathematically to its entirety. The educational impact will be significant for our graduate students not only in scientific and engineering fields, but also in mentoring and outreach since they are an integral part of our community efforts through the Rutgers Future Scholars program. Graduate students and undergraduates from minority and under represent groups will be actively recruited. These initiatives provide unique opportunities to these students that will excite them about education and training in engineering and help shape future leaders of our scientific and engineering communities. Finally, in support of results dissemination and outreach, the PI has secured funding to attend the CMMI bi-annual grantees' meeting.