Aortic Wall Distensibility in the Growth and Rupture of Abdominal Aortic Aneurysm

主动脉壁扩张与腹主动脉瘤生长和破裂的关系

• 批准号: 8784426
• 负责人: Christopher M Haggerty
• 金额: $ 1.78万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2015-04-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8784426
• 关键词: Abdomen; Abdominal Aortic Aneurysm; Affect; Aneurysm; Angiotensin II; Animal Disease Models; Animals; Aorta; Aortic Diseases; Apolipoprotein E; Area; Attenuated; Biomedical Engineering; Caliber; Cause of Death; Cell physiology; Clinical; Computer Simulation; Coupled; Data; Development; Diagnosis; Doxycycline; Elements; Enzymes; Extracellular Matrix; Extracellular Matrix Degradation; Future; Goals; Gold; Growth; Growth and Development function; Heterogeneity; Human; Image; Incidence; Inhibition of Matrix Metalloproteinases Pathway; Institution; Kentucky; Knowledge; Lead; Left; Luminal region; Magnetic Resonance Imaging; Matrix Metalloproteinases; Measurement; Measures; Mechanics; Medial; Mediating; Medical Imaging; Methods; Metric; Microscopic; Modeling; Mus; Natural History; Operative Surgical Procedures; Outcome; Patients; Physiologic pulse; Play; Predictive Value; Procedures; Property; Qualifying; Relative Risks; Reliance; Research; Resolution; Risk; Role; Rupture; Ruptured Abdominal Aortic Aneurysm; Ruptured Aneurysm; Sensitivity and Specificity; Shapes; Stress; Systolic Pressure; Testing; Therapeutic; Time; Translating; Ultrasonography; Universities; abdominal aorta; base; cardiovascular imaging; clinical care; clinical decision-making; clinical practice; effective therapy; improved; insight; mortality; mouse model; outcome forecast; programs; prophylactic; public health relevance; reconstruction; repaired; response

DESCRIPTION (provided by applicant): Abdominal aortic aneurysm (AAA) rupture is the 13th leading cause of death in the US. While prophylactic surgical repair is an effective treatment, there is significant mortality risks associated with the procedure. Since most aneurysms do not rupture, these surgical risks may outweigh the benefits of repair in many cases. However, there are currently no means to accurately identify an aneurysm that will rupture to effectively evaluate the relative risk of rupture versus repair. The big-picture goal of this research program is to improve clinical care for patients with AAA by establishing sensitive, non-invasive markers for aneurysm rupture that can be used to better identify patients who should undergo surgical repair. Aneurysm size, as determined by medical imaging, is currently the most common method used to evaluate AAA rupture risk. However, recent advances in magnetic resonance imaging (MRI) allow for more sophisticated, high resolution assessments of aortic mechanics, which are known to be more sensitive. For example, quantifying the dynamic changes in aortic size and shape with systolic pressure pulses can be used to assess the distensibility of the aortic wall. These images can also be used to create computer models of the aneurysm to calculate areas of high wall stress. Since AAA rupture occurs when aneurysm stress exceeds mechanical strength, we hypothesize that non-invasive quantification of these mechanical and structural properties will lead to better rupture predictions. The first step in evaluating our hypothesis is to demonstrate proof of concept for this imaging-based paradigm in an animal disease model. The most widely used model of AAA is the ApoE-/-/angiotensin-II mouse model, which was developed and has been extensively studied our institution over the past 15 years. This expertise, coupled with our cardiovascular imaging abilities in both mice and humans, uniquely qualifies us to successfully carry out this research. To develop mechanical rupture markers, we propose a two-pronged approach. We first seek to relate the macroscopic mechanics measured via MRI to the microscopic function of cells and enzymes, such a matrix metalloproteinases (MMPs), which are important deterministic factors in aneurysm grown and remodeling. Serial assessment of these mechanical measures in mouse AAA will then be related to rupture outcomes to evaluate their predictive value. The long-term objective of this proposal is to take these sensitive imaging markers and translate them to human studies to improve clinical decision-making.

描述（由申请人提供）：腹部主动脉动脉瘤（AAA）破裂是美国第13大死亡原因。虽然预防性手术修复是一种有效的治疗方法，但该手术存在很大的死亡率风险。由于大多数动脉瘤不会破裂，因此这些手术风险在许多情况下可能会大于修复的好处。但是，目前没有手段可以准确识别会破裂以有效评估破裂与修复的相对风险。该研究计划的重大目标是通过为动脉瘤破裂建立敏感的，无创的标记来改善AAA患者的临床护理，该标记可用于更好地识别应进行手术修复的患者。由医学成像确定的动脉瘤大小是评估AAA破裂风险的最常见方法。然而，磁共振成像（MRI）的最新进展允许对主动脉力学的更复杂的高分辨率评估，这更敏感。例如，用收缩压脉冲量化主动脉尺寸和形状的动态变化可用于评估主动脉壁的扩张性。这些图像也可以用于创建动脉瘤的计算机模型以计算高壁应力区域。由于当动脉瘤应力超过机械强度时发生AAA破裂，因此我们假设对这些机械和结构特性的非侵入性定量将导致更好的破裂预测。评估我们的假设的第一步是在动物疾病模型中证明这种基于成像的范式的概念证明。 AAA最广泛使用的模型是APOE - / - /Angiotensin-II小鼠模型，该模型已开发并在过去15年中已广泛研究了我们的机构。这种专业知识，再加上我们在小鼠和人类中的心血管成像能力，使我们有资格成功地进行这项研究。为了开发机械破裂标记，我们提出了一种两管齐的方法。我们首先寻求将通过MRI测量的宏观力学与细胞和酶的显微镜功能（这样的基质金属蛋白酶（MMP）（MMP）相关联，这些基质金属蛋白酶（MMPS）是动脉瘤生长和重塑的重要决定性因素。然后，对小鼠AAA中这些机械测量的连续评估将与破裂结果有关，以评估其预测价值。该提案的长期目标是采用这些敏感的成像标记，并将其转化为人类研究以改善临床决策。