Aortic Wall Microarchitecture and Cyclic Strain

描述(由申请人提供)： 人的主动脉易受动脉粥样硬化斑块沉积和动脉瘤扩大的影响。虽然具体的致病机制尚不清楚，但生物力学因素被认为发挥了重要作用，特别是在胸主动脉和腹主动脉对这些退行性变化的不同易感性方面。我们发展了一种无创的磁共振方法来量化在体的主动脉壁生物力学，发现主动脉壁的运动和应变在主动脉周长附近变化，主动脉结构的局部变化明显。这与临床上观察到的偏心斑块定位和局灶性动脉瘤形成是一致的。此外，血管内支架和支架移植物等用于治疗闭塞性疾病和主动脉瘤的植入性血管内装置也会影响主动脉的生物力学，但长期后果尚不清楚。 在这项资助中，我们将把活体测量的不同的主动脉应变模式与正常猪主动脉的三维微结构联系起来。然后，我们将在实验动物体内植入血管内支架和支架移植物，以改变主动脉壁的生物力学。我们将评估急性和慢性对在体主动脉壁生物力学的影响以及主动脉微结构的长期变化。我们将利用相同的在体磁共振成像技术来评估人类主动脉壁的运动和循环应变，并量化主动脉周长和长度上的差异。我们将研究青年和老年健康志愿者，以辨别年龄和性别相关的主动脉壁生物力学差异。这些数据将为我们理解与生物力学应变相关的主动脉结构和成分提供有价值的见解，并将提供一种评估使用植入性主动脉装置的介入治疗对主动脉壁的影响的手段。此外，这些研究将提供一个框架，以了解影响人类主动脉的正常年龄相关和退行性变化。最后，它将为主动脉磁共振成像在更大规模的人体临床试验中的应用提供量化基础，该试验涉及主动脉动脉瘤或闭塞症患者，包括血管内治疗前后的患者。

DESCRIPTION (provided by applicant): The human aorta is susceptible to both atherosclerotic plaque deposition and aneurysmal enlargement. While the specific causal mechanisms are unclear, biomechanical factors are thought to play an important role, particularly in the differing susceptibility of the thoracic and abdominal aorta to these degenerative changes. We developed a non-invasive magnetic resonance method to quantify aortic wall biomechanics in vivo and found that aortic wall motion and strain vary around the aortic circumference with significant local variation in aortic structure. This is consistent with clinical observations of eccentric plaque localization and focal aneurysm formation. Furthermore, aortic biomechanics are impacted by implanted endovascular devices such as stents and stent grafts which are used to treat occlusive disease and aneurysms of the aorta with unknown long term consequences. During this grant, we will relate varying aortic strain patterns measured in vivo to the 3-dimensional microarchitecture of normal porcine aortas. We will then implant endovascular aortic stents and stent grafts in experimental animals to modify aortic wall biomechanics. We will assess the acute and chronic impact on in vivo aortic wall biomechanics and long-term changes in aortic microstructure. We will utilize the same in vivo magnetic resonance imaging technique to assess aortic wall motion and cyclic strain in humans and quantitate the differences about the circumference and along the length of the aorta. We will study both young and elderly healthy volunteers in order to discern age and gender related differences in aortic wall biomechanics. These data will provide valuable insights into our understanding of the structure and compostition of the aorta in relation to biomechanical strain and will provide a means of assessing the impact on the aortic wall of interventional treatments using implanted aortic devices. Further, these studies will provide a framework to understand normal age-related and degenerative changes affecting the human aorta. Finally, it will provide a quantitative basis for application of aortic magnetic resonance imaging in larger human clinical trials involving patients with aneurysmal or occlusive disease of the aorta, both before and after endovascular treatment.