3D & 4D Coronary Hemodynamics and Local Atherosclerosis

描述（由申请人提供）：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到斑块形态和组成，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。在第一阶段的建议，我们开发了一种方法，冠状动脉形态和血流动力学的血管造影和血管内超声图像融合的3-D和4-D评估。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与其他因素，将开发和随后验证冠状动脉粥样硬化疾病的纵向研究。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深入了解血管形态、斑块组成、血流动力学和全身炎症及其他血管生物标志物对局部动脉粥样硬化进展的时间效应，从而预测动脉粥样硬化的负荷、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示的效率、再现性和3-D/4-D一致性。目标二：开发一种方法，用于复杂斑块成分的体内3-D和4-D评估，与几何正确的冠状动脉解剖结构和斑块形态配准，并能够在血管系统内结合功能和生理测量。目标3：通过对3-D和4-D冠状动脉几何形状、血流动力学、斑块形态和组成的多因素计算评估，以及对全身动脉粥样硬化相关生物标志物的测定，开发一种预测体内动脉粥样硬化斑块时间变化的方法。目的4：在50例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性质和组成、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，我们的工作将揭示动脉粥样硬化这些复杂和不同的促进剂的相互作用。这将对临床前动脉粥样硬化疾病患者的临床管理以及接受冠状动脉血运重建和急性冠状动脉综合征治疗的患者产生影响。

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.