Over the past few years, we have studied the initiation and growth of aortic aneurysms. Excised aneurysms of a popular aneurysm mouse model were imaged with a novel, high-resolution technique (Paul Scherrer Institute, Switzerland), demonstrating that the disease is the immediate consequence of a tear in the aortic wall near one of the side branches of the aorta (the celiac artery) which leads to internal bleeding within the aorta wall, a delamination of the different layers of the arterial wall and an apparent local dilatation (called “issecting aneurysm”. We also developed an advanced computational model framework to simulate blood flow within and stresses throughout the abdominal aortic wall. Preliminary simulations - in normal mice –showed stress concentrations near specific abdominal side branches which perfectly corresponded with the sites of rupture in the aortic wall that we visualized in mice that developed a dissecting aneurysm. In the current research proposal, we will implement a biomechanical model that includes (i) the complex anisotropy of the aorta and specifically accounts for the internal fiber organization in the vicinity of side branches; (ii) initiation of rupture and (iii) the progressive delamination of the aortic wall. The necessary data will be obtained from both available and new experiments in mice with “issecting aneurysms”where we will follow up the same animals prior to and during aneurysm formation.