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

该学院早期职业发展（Career）奖支持将应用实验和计算策略来量化心室周围白质及其年龄相关变性的生物力学特性的研究。脑老化的特点是进行性神经退行性变，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在器官水平上表现为大脑形状的改变，表现为皮层变薄，白质萎缩，最明显的是侧脑室增大。该研究旨在研究进行性组织丢失如何驱动心室增大，导致与神经炎症和轴突丢失相关的组织损伤，并在大脑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。这项工作可能有助于识别早期表现出异常衰老迹象的受试者。这项研究还将为教育活动提供信息，旨在向公众宣传基本的大脑衰老机制，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，以及为10年级学生和工程本科学生提供的研究机会。本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，从根本上了解衰老过程中器官水平组织体积损失与心室周围组织变性之间的关系。因此，本项目的研究目标包括：(i)从纵向图像数据推断心室增大；（ii）量化脑室周围组织的演化特性；（iii）建立脑老化本构模型，预测脑室增大和相应的脑室周围白质病变位置。在完成这项工作后，我们将清楚地了解(i)脑萎缩如何驱动脑室周围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态的可靠预测指标。此外，从这项工作中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产生的知识来识别早期心室周围白质病变形成风险增加的受试者。这个项目最终将允许PI推进计算和实验神经力学的新兴领域，并建立他在大脑健康方面的长期职业生涯。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值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.