Coronary Artery Dynamic Geometry and Atherosclerosis

描述（由申请人提供）： 本研究的长期目标是：（1）确定有利于动脉粥样硬化发展的冠状动脉血管系统的动态和几何特征，并可用于诊断和识别风险个体;（2）了解机械因素在动脉粥样硬化病理生物学和自然史中的作用。为了实现第一个目标，（a）将定义人体冠状动脉动力学和几何形状的正常变异性，以及（B）将寻求患病人体冠状动脉的动态几何形状与这些血管中病理的分布和进展之间的关系。第二个目标将通过（a）开发壁内应力分布的模型用于针对测量的体内壁应变进行测试，和（B）将apo-E缺陷小鼠的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来进一步实现。 将对140例血管造影正常的患者的双平面冠状动脉电影血管造影片进行处理，以重建左前降支和右冠状动脉树的选定段的中轴的时间依赖性三维（3-D）过程。将使用客观计算机算法从轴获得描述节段动态几何形状的参数，并定义其在总体中的正态分布。对于60例有明显疾病的患者的额外队列，血管造影片将由相同节段的血管内超声（IVUS）记录补充，将对其进行处理，以产生血管形态测量的详细测量结果和与血管轴搭配的3-D应变。在某些情况下，还将采集相位压力。考虑到动脉粥样硬化传统危险因素的变异性，将寻求从血管造影和IVUS记录中得出的参数之间的关系。这些数据还将用于开发和测试血管壁中的应力分布和适应模型。将暴露36只apo-E缺陷小鼠和8只野生型对照小鼠的心脏，并在双平面上观察。 将对双平面图像进行类似于临床图像的动态几何参数处理，并将寻求这些参数与组织的形态学、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.