3D & 4D Coronary Hemodynamics and Local Atherosclerosis

动脉粥样硬化性冠状动脉疾病的发展是复杂的。最近的研究表明， 临床事件的进展和风险受斑块形态和成分、局部血流动力学 压力、三维动脉运动、炎症和局部血管信号传导。在第一阶段，我们开发了一个 一种通过血管造影和血流动力学融合的冠状动脉形态和血流动力学的3-D和4-D评估方法 血管内超声图像。在第二阶段，我们将开发一种预测动脉粥样硬化进展的方法。 这个预测模型，结合我们现在成熟的方法和其他因素，将被开发， 随后在冠状动脉粥样硬化疾病受试者的纵向研究中得到验证。 我们的主要假设是，冠状动脉疾病患者的系列体内研究可以提供以下见解： 血管形态、斑块组成、血流动力学和全身炎症等的时间效应 局部动脉粥样硬化进展的血管生物标志物，从而允许预测负荷的变化， 动脉粥样硬化的位置和程度。因此，我们建议： 目的1：进一步改进先前开发的血管造影-IVUS融合图像分析方法 以提高效率，再现性和3-D/4-D的几何表示的一致性， 体内的冠状动脉。 目的2：开发一种在体内三维和四维评估配准中复杂斑块组成的方法 具有几何学上正确的冠状动脉解剖结构和斑块形态， 血管系统内的功能和生理测量。 目的3：建立一种从多因素预测动脉粥样硬化斑块时间变化的方法 三维和四维冠状动脉几何形状、血流动力学、斑块形态的计算机评估 和组成，同时测定全身动脉粥样硬化相关的生物标志物。 目的4：在50例已建立的动脉粥样硬化性心脏病患者的系列研究中验证斑块进展预测方法。 动脉粥样硬化 我们的工作将揭示初始局部斑块性质和成分、血管和 全身炎症环境和血流动力学状况与中期动脉粥样硬化疾病进展或 回归分析一旦成功开发，我们的工作将揭示这些复杂而不同的启动子之间的相互作用 动脉粥样硬化这将对临床前动脉粥样硬化患者的临床管理产生影响 疾病以及经历冠状动脉血运重建和急性冠状动脉综合征治疗的那些患者。

The development of atherosclerotic coronary artery disease is complex. Recent work indicates that plaque progression and risk of clinical events are influenced by plaque morphology and composition, local hemodynamic stresses, 3-D arterial motion, inflammation, and local vascular signaling. In Phase I of this proposal, we developed a method for 3-D and 4-D assessment of coronary artery morphology and hemodynamics by fusion of angiographic and intravascular ultrasound images. In Phase II, we will develop a method for predicting atherosclerosis progression. This predictive model, incorporating our now mature methodology with other factors, will be developed and subsequently validated in longitudinal studies of subjects with coronary atherosclerotic disease. Our main hypothesis is that serial in-vivo studies of patients with coronary artery disease can provide insights into the temporal effects of vessel morphology, plaque composition, hemodynamics, and systemic inflammatory and other vascular biomarkers on local atherosclerosis progression, thus allowing the prediction of changes in the burden, location and extent of atherosclerosis. Therefore, we propose to: Aim 1: Further improve the previously developed image analysis methodology for angiography-IVUS fusion to increase efficiency, reproducibility, and 3-D/4-D consistency of the geometric representations of coronary arteries in vivo. Aim 2: Develop a method for in vivo 3-D and 4-D assessment of complex plaque composition in registration with geometrically correct coronary anatomy and plaque morphology with the ability to incorporate functional and physiologic measures within the vasculature. Aim 3: Develop a method for predicting temporal changes in atherosclerotic plaque in vivo from multifactorial computational assessment of 3-D and 4-D coronary geometry, hemodynamics, plaque morphology and composition, with the concomitant determination of systemic atherosclerosis-related biomarkers. Aim 4: Validate the plaque progression prediction method in a serial study of 50 patients with established atherosclerosis. Our work will uncover the relative contribution of initial local plaque properties and composition, the vascular and systemic inflammatory milieu and hemodynamic conditions to intermediate-term atherosclerotic disease progression or regression. Once successfully developed, our work will uncover the interplay of these complex and disparate promoters of atherosclerosis. It will have implications on the clinical management of patients with preclinical atherosclerotic disease as well as those patients undergoing coronary revascularization and treatment of acute coronary syndromes.