CAREER: Biomechanical Characterization of Periventricular White Matter and its Age-related Degeneration

职业：脑室周围白质的生物力学特征及其与年龄相关的变性

• 批准号: 2337739
• 负责人: Johannes Weickenmeier
• 金额: $ 57.06万
• 依托单位: Stevens Institute of Technology
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-06-01 至 2029-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2337739&HistoricalAwards=false
• 关键词: CAREER; Biomechanical; Characterization; Periventricular; White

This Faculty Early Career development (CAREER) award supports research that will apply experimental and computational strategies to quantify the biomechanical properties of periventricular white matter and its age-related degeneration. Brain aging is characterized by progressive neurodegeneration that inescapably leads to cognitive slowing and functional decline. As such, corresponding cell-level changes manifest on the organ-level as brain shape changes in the form of cortical thinning, white matter shrinking, and – most notably – lateral ventricular enlargement. The research seeks to study how progressive tissue loss drives ventricular enlargement, leads to tissue damage associated with neuroinflammation and axon loss and is clearly visible in medical imaging of the brain. The framework will explain the impact of decade-long brain shape changes on functional brain structures, such as the ventricular wall. This work could lead to potential identification of subjects showing signs of abnormal aging early on. The research will also inform educational activities that aim at educating the public about basic brain aging mechanisms and fostering early interest in science, engineering, and medicine among underrepresented groups in STEM. That includes contributions to the annual Brain Awareness Week as well as research opportunities catered to 10th-graders and undergraduate engineering students. The specific goal of the research is to combine medical image registration, mechanical characterization, and constitutive modeling to fundamentally understand the relationship between organ-level tissue volume loss and periventricular tissue degeneration during aging. Thus, the research objectives of this project include to (i) infer ventricular enlargement from longitudinal image data; (ii) to quantify the evolving properties of periventricular tissues; and (iii) to establish a constitutive brain aging model that predicts ventricular enlargement and corresponding periventricular whiter matter lesion locations. Upon completion of the work, it will become clear (i) how cerebral atrophy drives microstructural degeneration of periventricular white matter tissue and (ii) how the severity of age-related brain shape changes is a reliable predictor for the brain’s overall state of health. Additionally, the tools arising from this work will be an important addition to the soft tissue biomechanics community. The overarching focus will be on using the newly generated knowledge to identify subjects that are at increased risk for early periventricular white matter lesion formation. This project will ultimately allow the PI to advance the emerging field of computational and experimental neuromechanics and establish his long-term career in brain health.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.

这项教师早期职业发展（职业）奖支持将采用实验和计算策略的研究，以量化周围白质及其与年龄相关的变性的生物力学特性。大脑衰老的特征是进行性神经退行性变化，这不可避免地导致认知减慢和功能下降。因此，相应的细胞水平变化表现在器官级别上，因为大脑形状在皮质变薄，白质缩小的形式下变化，并且（最著名的是 - 最值得注意的 - 侧心室膨胀。该研究试图研究渐进组织损失如何推动心室扩张，从而导致与神经炎症和轴突丧失相关的组织损伤，并且在大脑的医学成像中清晰可见。该框架将解释长达十年的大脑形状变化对功能性大脑结构（例如心室壁）的影响。这项工作可能会导致对受试者的潜在识别，显示出早期衰老异常的迹象。这项研究还将为旨在向公众提供有关基本大脑老化机制的教育活动，并在STEM中代表性不足的群体中培养对科学，工程和医学的早期兴趣。这包括对年度大脑意识周的贡献，以及迎合10年级和本科工程专业学生的研究机会。该研究的具体目标是结合医学图像注册，机械表征和组成型建模，以从衰老期间从根本上了解器官水平的组织体积损失与周期性组织变性之间的关系。这是该项目的研究目标包括（i）从纵向图像数据中推断心室扩张； （ii）量化周期组织的发展特性； （iii）建立一个预测心室增加并相应的脑室白质病变位置的组成型脑老化模型。完成工作后，（i）脑萎缩如何驱动脑室白质组织的微观结构变性，以及（ii）与年龄相关的大脑形状变化的严重程度如何成为大脑整体健康状况的可靠预测因子。此外，这项工作产生的工具将是软组织生物力学社区的重要补充。总体重点将是利用新生成的知识来识别面临早期白质病变形成风险增加的受试者。该项目最终将使PI能够推进计算和实验性神经力学的新兴领域，并在大脑健康方面建立他的长期职业。该奖项反映了NSF的法定任务，并通过使用该基金会的知识分子的优点和更广泛的影响来审查标准，认为通过评估来表现出宝贵的支持。