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

该学院早期职业发展(CALEAR)奖支持将应用实验和计算策略来量化脑室周围白质及其年龄相关变性的生物力学特性的研究。大脑老化的特征是进行性神经退化，不可避免地会导致认知减慢和功能衰退。因此，相应的细胞水平的变化在器官水平上表现为大脑形状的变化，表现为皮质变薄，脑白质缩小，以及--最显著的--侧脑室扩大。这项研究试图研究进行性组织丢失如何导致脑室扩大，导致与神经炎症和轴突丢失相关的组织损伤，并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脑功能结构(如脑室壁)的影响。这项工作可能导致对早期表现出异常衰老迹象的受试者进行潜在识别。这项研究还将为旨在教育公众了解基本大脑老化机制的教育活动提供信息，并在STEM中代表性不足的群体中培养早期对科学、工程和医学的兴趣。这包括对一年一度的大脑意识周的贡献，以及为10年级学生和工科本科生提供的研究机会。这项研究的具体目标是将医学图像配准、力学表征和本构建模相结合，从根本上了解器官水平的组织体积损失和老化过程中脑室周围组织退变之间的关系。因此，本项目的研究目标包括：(I)从纵向图像数据推断脑室扩大；(Ii)量化脑室周围组织的演变特性；(Iii)建立预测脑室扩大和相应脑室周围白质损害位置的结构性脑老化模型。这项工作完成后，(I)大脑萎缩如何导致脑室周围白质组织的微结构退化，以及(Ii)与年龄相关的脑形状变化的严重性如何是大脑整体健康状态的可靠预测指标将变得清晰。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。主要的重点将是使用新产生的知识来识别早期脑室周围白质病变形成的风险增加的受试者。该项目最终将允许PI推进计算和实验神经力学的新兴领域，并建立他在脑健康方面的长期职业生涯。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。

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.