3D & 4D Coronary Hemodynamics and Local Atherosclerosis

描述(申请人提供)：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，斑块的进展和临床事件的风险受斑块形态和组成、局部血流动力学应力、三维动脉运动、炎症和局部血管信号的影响。在这项建议的第一阶段，我们开发了一种通过融合血管造影和血管内超声图像来评估冠状动脉形态和血流动力学的3-D和4-D方法。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。这一预测模型将我们现在成熟的方法与其他因素结合起来，将被开发出来，并随后在冠状动脉粥样硬化性疾病受试者的纵向研究中得到验证。我们的主要假设是，对冠心病患者进行的一系列体内研究可以深入了解血管形态、斑块组成、血流动力学以及全身炎症和其他血管生物标志物对局部动脉粥样硬化进展的时间影响，从而能够预测动脉粥样硬化的负担、位置和程度的变化。因此，我们建议：目标1：进一步改进先前开发的用于血管造影-IVUS融合的图像分析方法，以提高在体冠状动脉几何表示的效率、重复性和3-D/4-D一致性。目的2：建立一种体内3-D和4-D评估复杂斑块成分的方法，该方法与几何正确的冠状动脉解剖和斑块形态相匹配，能够将功能和生理措施结合到血管系统中。目的：通过对冠状动脉三维和四维几何结构、血流动力学、斑块形态和成分的多因素计算，结合系统性动脉粥样硬化相关生物标志物的测定，建立一种预测动脉粥样硬化斑块在体内的时间变化的方法。目的4：在50例已确诊的动脉粥样硬化患者的系列研究中验证斑块进展预测方法。我们的工作将揭示初始局部斑块的属性和组成、血管和全身炎症环境以及血流动力学条件对中期动脉粥样硬化性疾病进展或消退的相对贡献。一旦开发成功，我们的工作将揭示这些复杂和不同的动脉粥样硬化促进剂之间的相互作用。这将对临床前动脉粥样硬化性疾病患者以及接受冠状动脉血运重建术和急性冠脉综合征治疗的患者的临床处理具有一定的指导意义。

DESCRIPTION (provided by applicant): 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.