Bio-mechanical studies of normal and aging arterial wall

主动脉是人体最大的血管，它离开心脏，将富含氧气的血液输送到解剖结构的所有其他区域的细胞中。从本质上讲，主动脉是一个圆柱形的管子，壁光滑，非常坚固。然而，随着年龄的增长，它开始失去力量。这与组织组织的整体减少和弹性蛋白的丢失有关，弹性蛋白是主要的承重元素，同时增加了其他不太理想的成分。这项拟议的研究将回答以下基本问题：(A)我们如何在整个生命周期内监测血管的特性(例如，硬化)？(B)我们能否开发出不需要实际机械测试就能从图像中估计这些特性的方法？以及(D)动脉组织随着年龄的增长发生的分子过程是什么，根据它们的成像和血流特征能“识别”它们吗？具体的五年目标如下：1.为健康的动脉组织开发和测试一个新的数学模型，该模型描述了由于生长(重塑)和老化而发生的变化。2.开发通过适当线性化本构模型和体内血流模式来估计局部动脉壁硬度的技术。3.研究细胞信号和炎症过程，它们是健康动脉组织生理重塑过程的一部分。这项研究的好处是，它将使跟踪健康动脉特性的变化成为可能。大多数健康组织不能从普通人群中获得，从尸检中获得的组织数量和质量有限。因此，非侵入性技术提供了一个独特的机会。此外，目前监测动脉硬化(例如脉搏波速度)的方法没有将它们与微结构组件联系起来，也不允许对体内拉伸进行评估。这一点很重要，因为较高的压力可能表现为在不改变组织特性的情况下表观硬度增加。提出并应用了一种既能描述再塑又能描述时效的新本构模型。结果将是正常和老化的主动脉图谱，这些图谱可以用来实现早期诊断，并最终确定治疗方案的优先顺序。该项目将培养跨学科研究的本科生、研究生和博士后实习生。这些学生将在数学建模、非线性力学、流体力学、生物学、显微镜和统计方法方面积累专业知识。他们将在工程学和自然科学的边界上积累知识，并将重点放在批判性思维上。这些技能可以在生物工程领域的许多学科中翻译，也可以在外部，例如复合材料力学和聚合物材料科学中翻译。

The aorta is the largest vessel in the body, exiting the heart and carrying oxygen-rich blood to cells in all other regions of the anatomy. Essentially, the aorta is a cylindrical tube with smooth walls and is extremely strong. Yet, it starts losing strength with age. This is associated with an overall decrease of the tissue organization with loss of elastin, which is the primary load bearing element, along with an increase of other less desirable components. The proposed research will answer the following fundamental questions: (a) how do we monitor the properties (for example stiffening) of blood vessels across the lifespan? (b) can we develop methods to estimate these properties from images without the need for actual mechanical tests? and (d) what are the molecular processes that occur in arterial tissues as they age, and can they be `recognized' from their imaging and flow signatures? The specific five-year objectives are as follows: 1.Develop and test a new mathematical model for healthy arterial tissue that describes changes due to growth (remodelling) and aging. 2.Develop techniques to estimate local arterial wall stiffness - by properly linearizing the constitutive model - and flow patterns, in vivo. 3.Study cell signalling and inflammatory processes which are part of the physiological remodelling processes in healthy arterial tissues. The advantage of this research is that it will make it possible to follow changes in the properties of healthy arteries. Most healthy tissues cannot be obtained from the general population and the amount and quality of tissues obtained from autopsy is limited. Therefore non-invasive techniques offer a unique opportunity. Moreover, current methodologies that monitor stiffening of arteries (for example pulse-wave velocity) do not link them to the micro-structural components and do not allow assessment of the in vivo stretch. This is important because higher pressure may manifest itself as increased apparent stiffness without changes in the tissue property. A new constitutive model capable of describing both remodelling and aging will be proposed and applied. Outcomes will be atlases of normal and aging aortas which could be used to achieve early diagnoses and eventually prioritize treatment options. This project will prepare undergraduate, graduate and post-doctoral trainees in interdisciplinary research. The students will build expertise in mathematical modelling, non-linear mechanics, fluid mechanics, biology, microscopy and statistical methodologies. They will build knowledge at the boundaries of engineering and natural science with a strong focus on critical thinking. These skills are translatable in many disciplines both in the area of bioengineering, as well as outside, in composite mechanics and polymeric material science, for example.