Collaborative Research: Multiscale Mechanical Models for the Aging Brain

随着美国8100万婴儿潮一代步入老年，50%的85岁以上成年人患有阿尔茨海默氏症，这一事实给人们带来了一场迫在眉睫的危机。早期诊断或开发有效的神经保护或再生干预措施的希望，需要更深入地了解健康的人的大脑是如何正常衰老的。一种新的基于磁共振成像的非侵入性弹性成像方法可以高分辨率测量活着的大脑的局部机械特性，这表明大脑的僵硬程度随着年龄的增长而降低。该奖项专注于基础知识的发展，将脑组织微结构与非侵入性测量的局部机械特性联系起来。利用当地诊所提供的成像技术，然后可以生成大脑的机械地图，并将其用作基线，以确定与年龄相关的大脑退化阶段，或监测干预的效果。这一奖项将加强两位首席研究人员的外展努力，继续吸引对计算力学、软组织力学、图像处理和神经科学交叉感兴趣的传统上代表性不足的群体的工程师。除了丰富与力学有关的课程和培训未来工程师在与国家健康大脑倡议相一致的研究方面外，该项目预计将直接影响这两个机构的更广泛的医学界。两个重要的技术进步提供了对脑神经元发育和退化的洞察：细胞水平的机械生物学和高分辨率活体磁共振弹性成像。挑战是将这两个层次的分析统一起来，以便获得正常衰老期间人脑白质的严格生物力学视图。该奖项支持基于医学成像和已发表的组织学数据的白质微观力学分层多尺度模型的开发。这些模型将能够根据轴突微结构中的某些参数来解释磁共振弹性成像数据。局部粘弹性特性将与轴突网络的结构指标在空间上相关联，因此可以跨受试者和年龄组研究大脑的生物力学特性。这种多尺度建模工作的主要结果是将轴突的结构完整性与磁共振成像量化的局部平均功能特性联系起来。这将有助于解释大脑白质中与年龄相关的变化如何与神经元和神经胶质细胞随着年龄增长而发生的连接和机械耦合的变化有关。

As 81 million 'baby boomers' living in the US enter old age, the fact that 50 percent of adults over the age of 85 are afflicted with Alzheimer's disease presents a looming crisis. Early diagnosis or the hope of developing an effective neuroprotective or regenerative intervention requires a deeper understanding of how the healthy human brain ages normally. A novel noninvasive elastography method based on magnetic resonance imaging has allowed high-resolution measurements of local mechanical properties of the living brain, which reveal that brain stiffness decreases with age. This award focuses on the development of fundamental knowledge to connect brain tissue microstructure with local mechanical properties measured noninvasively. Employing imaging technology available in the local clinic, mechanical maps of the brain can then be generated and used as a baseline to determine the stage of age-related brain degeneration, or to monitor the efficacy of an intervention. This award will enhance the outreach efforts of both principal investigators towards continuing to attract engineers from traditionally underrepresented groups interested in the intersection of computational mechanics, soft-tissue mechanics, image processing, and neuroscience. In addition to the enrichment of the mechanics-related curriculum and training of future engineers in research aligned with the national healthy brain initiatives, this project is expected to directly impact the broader medical communities at the two institutions. Two important technical advances have provided insight into the development and degeneration of brain neurons: cell-level mechanobiology and high-resolution in vivo magnetic resonance elastography. The challenge is to unify these two levels of analysis in order to obtain a rigorous biomechanical view of the white matter of the human brain during normal aging. This award supports the development of hierarchical multiscale models of white matter micromechanics based on medical imaging and published histological data. These models will enable the interpretation of the magnetic resonance elastography data in terms of certain parameters in axon microstructure. Local viscoelastic properties will be spatially correlated with architectural metrics of the axonal network, so that the biomechanical properties of the brain can be investigated across subjects and age groups. The main outcome of this multiscale modeling effort is to relate the structural integrity of the axons to locally averaged functional properties quantified by magnetic resonance imaging. This will help explain how the age-related changes in the brain white matter are related to alterations in connectivity and mechanical coupling between neurons and glial cells as they age.