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、3-D动脉运动、炎症和局部血管信号的影响。在本提案的第一阶段，我们开发了一种通过血管造影和血管内超声图像融合来评估冠状动脉形态和血流动力学的3d和4d方法。在II期，我们将开发一种预测动脉粥样硬化进展的方法。该预测模型结合了我们目前成熟的方法和其他因素，将在冠状动脉粥样硬化疾病患者的纵向研究中得到发展和验证。我们的主要假设是，对冠状动脉疾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、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血管造影- ivus融合图像分析方法，以提高体内冠状动脉几何表征的效率、可重复性和3-D/4-D一致性。目标2：开发一种体内3-D和4-D评估复杂斑块组成的方法，在几何上正确的冠状动脉解剖和斑块形态注册中，能够结合血管系统内的功能和生理测量。目标3：开发一种预测体内动脉粥样硬化斑块时间变化的方法，通过对三维和4d冠状动脉几何、血流动力学、斑块形态和组成的多因素计算评估，同时确定与系统性动脉粥样硬化相关的生物标志物。目的4：在50例已确诊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特性和组成、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疾病进展或消退的相对贡献。一旦成功开发，我们的工作将揭示这些复杂和不同的动脉粥样硬化促进因子的相互作用。这将对临床前动脉粥样硬化性疾病患者的临床管理以及接受冠状动脉血管重建术的患者和急性冠状动脉综合征的治疗具有重要意义。

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.