Coronary Artery Dynamic Geometry and Atherosclerosis

描述(由申请人提供)： 这项研究的长期目标是：(1)识别有利于动脉粥样硬化发展的冠状动脉血管的动态和几何特征，并可用于预测和识别处于危险中的个体；(2)了解机械因素在动脉粥样硬化的病理生物学和自然历史中的作用。为了实现第一个目标，(A)将定义人类冠状动脉动力学和几何的正常变异性，以及(B)将寻找病变冠状动脉的动态几何与这些血管中的病理分布和进展之间的关系。第二个目标将通过(A)开发壁内应力分布模型来测试体内测量的壁应变，以及(B)将apo-E缺陷小鼠冠状动脉的动态几何形状与组织组织学和基因表达相关联，以进一步实现第二个目标。 对140例冠状动脉造影正常的患者进行双平面冠状动脉造影，重建左、前降支和右冠状动脉树选定节段中轴的时间相关三维(3-D)过程。描述线段动态几何形状的参数将使用客观的计算机算法从轴线获得，并将定义其在总体中的正态分布。对于另外60名有明显疾病的患者，血管造影将得到相同节段的血管内超声(IVUS)记录的补充，这些记录将被处理，以产生血管形态测量和与血管轴配置的3-D应变的详细测量。在某些情况下，还会获得相压力。考虑到动脉粥样硬化的传统危险因素的可变性，将寻求从血管造影术和血管内超声记录中获得的参数之间的关系。这些数据还将用于开发和测试血管壁应力分布和适应的模型。36只apo-E基因缺陷小鼠和8只4岁的野生型对照小鼠的心脏将在双平面上暴露和观察。 将对双平面图像进行类似于临床图像的动态几何参数的处理，并将寻找这些参数与组织的形态测量、组织学和基因表达谱之间的关系。

DESCRIPTION (provided by applicant): The long-term objectives of this research are: (1) to identify dynamic and geometric features of the coronary vasculature that favor atherosclerotic development and can be used prognostically and to identify individuals at risk, and (2) to understand the role of mechanical factors in the pathobiology and natural history of atherosclerosis. To achieve the first objective, (a) the normal variability in human coronary artery dynamics and geometry will be defined, and (b) relationships will be sought between the dynamic geometry of diseased human coronary arteries and the distribution and progression of pathology in these vessels. The second objective will be furthered by (a) developing models of intramural stress distribution for testing against measured in vivo wall strain, and (b) correlating the dynamic geometry of the coronary arteries of apo-E deficient mice against tissue histology and gene expression. Biplane coronary cineangiograms of 140 patients with angiographically normal vessels will be processed to reconstruct the time-dependent three-dimensional (3-D) course of the medial axes of selected segments of the left anterior descending and right coronary artery trees. Parameters describing the dynamic geometry of the segments will be obtained from the axes using objective computer algorithms, and their normal distributions in the population will be defined. For an additional cohort of 60 patients with evident disease, angiograms will be complemented by intravascular ultrasound (IVUS) records of the same segments, which will be processed to yield detailed measurements of vessel morphometry and 3-D strain collocated to the vessel axes. In some cases, phasic pressure will also be acquired. Relations will be sought between the parameters derived from the angiograms and from the IVUS records, taking into account variability in the traditional risk factors for atherosclerosis. These data will also be used to develop and test models of stress distribution and adaptation in the vessel wall. The hearts of 36 apo-E deficient and 8 wild type control mice at four ages will be exposed and viewed in biplane. The biplane images will be processed for dynamic geometry parameters similarly to the clinical images, and relationships will be sought between these parameters and the morphometry, histology and gene expression profiles of the tissue.