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CAREER: Multiscale Modeling of Axonal Fiber Bundles in the Brain

职业：大脑轴突纤维束的多尺度建模

基本信息

批准号：
1846059
负责人：
Reuben Kraft
金额：
$ 50万
依托单位：
Pennsylvania State Univ University Park
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2019
资助国家：
美国
起止时间：
2019-02-15 至 2024-01-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1846059&HistoricalAwards=false
关键词：
CAREER Multiscale Modeling Axonal Fiber

项目摘要

Brain injuries are a significant health concern for civilian and military populations. Many of these injuries result from damage to the axons, the long extensions of neurons that allow communication between brain cells. This Faculty Early Career Development Program (CAREER) project will contribute to the understanding of brain trauma by developing advanced computer models that link neuroimaging results, biomechanical assessments, and computational modeling of the brain. Specifically, this project will develop and validate a model of axonal damage using controlled experimental methods. More broadly, the continued pursuit of the development and validation of numerical diagnostics is anticipated to advance the emerging field of computational medicine. This project will integrate education and outreach activities with the research, including a mobile "NSF Sideline Science" curriculum that teaches and promotes awareness of brain science and computational medicine for K-12 students and the general public. In addition, a systematic multiyear study will examine the effectiveness of a new junior-level computational tools course on improving undergraduate performance in other core engineering and design courses. Also, a graduate-level, semiannual colloquium will enhance students' understanding of the power of advanced cyberinfrastructures to solve diverse problems in science and engineering.Diffuse axonal injury is a common pathology associated with traumatic brain injury in which deformation of axonal cells leads to rupture and axonal degeneration; yet, there remain difficulties with interpreting the degree of injury based on imaging of structural changes. Axonal fiber tracts formed from organized collections of neural cells can be visualized using magnetic resonance diffusion imaging. These images will be used in conjunction with a new multiscale embedded finite element technique that models the complex nature of axonal tracts in the brain. The research objective is to develop a validated multiscale computational method that explicitly includes axonal fiber tracts from diffusion-weighted neuroimaging and predicts primary and secondary effects of axonal injury over time. The central hypothesis is that changes in diffusion tensor imaging can be fully explained through the use of computational predictions of axonal fiber bundle strain. This project will develop a new computational tool, or "Digital Brain," that leverages advanced cyberinfrastructures and expands capabilities in the emerging field of computational medicine. This will be accomplished through the implementation of a new multiscale embedded finite element technique to model the complex nature of axonal tracts in the brain as well as a time-dependent, inelastic damage model for the axonal fiber tracts and surrounding extra cellular matrix. Both will be validated using controlled experimental methods. The model will extend from the molecular to the organ level to study axonal injury mechanisms. Single cell-to-fiber tract coupling will enable the transfer of structural and functional information across scales. This multiscale modeling will thus provide insight into primary and secondary Wallerian injury cascades associated with brain injury.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.

脑损伤是平民和军人的重大健康问题。这些损伤中的许多都是由于轴突受损造成的，轴突是神经元的长期延伸，允许脑细胞之间的交流。该学院早期职业发展计划(CALEAR)项目将通过开发先进的计算机模型，将神经成像结果、生物力学评估和大脑的计算建模联系起来，帮助理解脑创伤。具体地说，该项目将利用受控实验方法开发和验证轴突损伤模型。更广泛地说，对数值诊断的发展和验证的持续追求有望推动计算医学这一新兴领域的发展。该项目将把教育和外展活动与研究相结合，包括一个流动的“NSF副业科学”课程，教授和促进K-12学生和普通公众对脑科学和计算医学的认识。此外，一项系统的多年研究将检验一门新的初级计算工具课程在提高本科生在其他核心工程和设计课程中的表现方面的有效性。此外，研究生级别的半年一次的研讨会将增强学生对先进网络基础设施解决科学和工程中各种问题的能力的理解。弥漫性轴突损伤是一种与创伤性脑损伤相关的常见病理，轴突细胞变形导致轴突破裂和轴突变性；然而，基于结构变化的成像来解释损伤程度仍然存在困难。轴突纤维束由有组织的神经细胞集合形成，可以使用磁共振扩散成像进行可视化。这些图像将与一种新的多尺度嵌入式有限元技术结合使用，该技术将模拟大脑中轴突束的复杂性质。研究目标是开发一种有效的多尺度计算方法，该方法显式包括来自扩散加权神经成像的轴突纤维束，并预测轴突损伤随时间的原发和继发影响。中心假设是，扩散张量成像的变化可以通过使用轴突纤维束应变的计算预测来完全解释。该项目将开发一种新的计算工具，即“数字大脑”，它利用先进的网络基础设施，并在新兴的计算医学领域扩展能力。这将通过实施一种新的多尺度嵌入式有限元技术来模拟大脑轴索的复杂性质，以及轴突纤维束和周围细胞外基质的随时间变化的非弹性损伤模型来实现。这两种方法都将使用受控实验方法进行验证。该模型将从分子水平延伸到器官水平，研究轴突损伤的机制。单细胞到纤维束的耦合将使结构和功能信息的跨尺度传输成为可能。因此，这种多尺度建模将提供对与脑损伤相关的原发和继发性沃勒损伤级联的洞察。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。