GOALI: Development of an Ultrasound-Based System for Dynamic Intra-Coronary Plaque Characterization

虽然冠状动脉树的所有部分都暴露在相同的系统性风险因素(高低密度脂蛋白、高血压、尼古丁代谢物等)下，但冠心病的所有临床重要方面都表现为冠脉树内特定位置的局部现象。最值得注意的是：最初的动脉粥样硬化病变偏心地出现在冠状动脉弯曲处和分叉处附近。病变进展最常见的是偏心和局部性的，至少在疾病最晚期之前是这样。心肌梗死(即心脏病发作)的发生是由于特定的病变破裂，通常不会阻塞超过50%的动脉，随后在病变上方形成闭塞血栓(血块)的管腔。对尸检冠状动脉的广泛研究表明，所有这些现象都与详细的血流模式密切相关，主要是血液对动脉内皮细胞衬里施加的剪应力。低剪应力促进动脉粥样硬化的形成和生长，而高剪应力和(可能)剪应力梯度促进斑块破裂，继而在潜在的动脉闭塞处形成血栓。到目前为止，无论是在人类还是在实验动物中，活体局部血流和剪应力模式都是不可能的，因为测量导管插入冠状动脉会完全扭曲被测的流场，而目前的磁共振成像技术(MRI)没有足够的分辨率。我们建议开发一种基于超声的系统，用于实时确定血流动力学特性和动脉粥样硬化斑块的生长。首先，通过重建定向动脉粥样硬化切除超声和双平面冠状动脉造影术后的图像数据，确定动脉的三维解剖。该管腔几何图形随后将被处理成适合于计算的网格结构。详细的血管内流动特性将从控制质量和动量守恒的输运方程的数值解中得到。图像处理和数值模型将进行独立验证，最终结果将记录在数据库中并显示在计算机上，以跟踪动脉粥样硬化斑块的进展。该提案的长期目标是提供一种工具，可以用来进一步研究血流动力学和动脉粥样硬化斑块之间的关系。我们预计，一个奖项将提供杠杆作用，以寻求额外的资金来测试通过动物研究开发的系统。这项提议是东北大学和两家哈佛附属医院之间的合作项目，前者擅长数值建模和图像分析，后者擅长心脏病学、ICU和双平面血管造影术，后者擅长医疗器械。Quinton将就将我们的系统与血流动力学和成像系统集成的实际方面向该项目提供密切建议。这将加快我们系统的上市时间，并确保它与世界各地广泛的导尿管实验室的需求相兼容。如果该项目成功，这将是对Quinton产品线的合理补充。我们在医院的合作者将同时进行ICU和双平面血管造影术，以提供图像数据。该项目预计在36个月内完成。

9902011IlegbusiAlthough all segments of the coronary artery tree are exposed to the same systemic risk factors (high LDL cholesterol, hypertension, nicotine metabolites, etc.), all the clinically important aspects of coronary heart disease are manifest as local phenomena at specific locations within the coronary tree. Most notably: The initial atherosclerotic lesions appear eccentrically at bends and near bifurcations of the coronary arteries. Lesion progression is most commonly eccentric and localized, at least until the most advanced stages of the disease. Myocardial infarction (i.e. heart attack) occurs as a result of rupture of a specific lesion, often one that does not occlude more than 50% of the artery, followed by the formation of a lumen occluding thrombus (blood clot) over the lesion.Extensive study of the post-mortem coronary arteries has made it clear that all of these phenomena are intimately dependent on the detailed blood flow pattern, primarily the shear stress exerted by the blood on the endothelial lining of the artery. Low shear stress promotes initial atheroma formation and growth while high shear stress and (probably) shear stress gradient promote plaque rupture with subsequent thrombus formation on potential artery occlusion.To date, it has been impossible to investigate local blood flow and shear stress patterns in vivo, either in humans or experimental animals, because the insertion of a measuring catheter into the coronary artery completely distorts the flow-field being measured, while current magnetic resonance imaging techniques (MRI) do not have adequate resolution. We propose developing an ultrasound-based system for determining hemodynamic characteristics and atherosclerotic plaque growth in real time. First, the three-dimensional anatomy of the artery will be determined by reconstructing the image data obtained after directional atherectomy ultrasound and biplane coronary angiography. This luminal geometry will then be processed into a grid structure suitable for use in computation. The detailed intravascular flow characteristics will be obtained from numerical solution of the transport equations governing the conservation of mass and momentum. The image processing and numerical models will be verified independently and the final results will be recorded in a database and displayed on the computer to follow the progression of atherosclerotic plaque. The long-term objective of the proposal is to provide a tool with which the relationship between hemodynamics and atherosclerotic plaque can be further investigated. We envisage that an award will provide leveraging to seek additional funds to test the system thus developed through animal studies. This proposal is a collaborative program between Northeastern University, with expertise in numerical modeling and image analysis, two Harvard affiliated hospitals, with expertise in cardiology, ICUS and biplane angiography, and Quinton Instruments Co. with expertise in medical instrumentation. Quinton will closely advise the project on the practical aspects of integrating our system with both hemodynamic and imaging systems. This will accelerate the time-to-market of our system and ensure that it is compatible with the needs of a broad spectrum of catheterization laboratories worldwide. If the project is successful, it will be a logical addition to the Quinton product line. Our collaborators at the hospitals will perform simultaneous ICUS and biplane angiography to provide image data. The project is expected to be completed in 36 months.