Predicting Cardiovascular Risk in Vulnerable Plaque Rupture

预测易损斑块破裂的心血管风险

基本信息

批准号：
7937740
负责人：
Sheldon Weinbaum
金额：
$ 35.66万
依托单位：
CITY COLLEGE OF NEW YORK
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7937740
关键词：
Acute Address Algorithms American Area Arterial Fatty Streak Award Biomechanics Blood Pressure Breast Microcalcification Cadaver Calcified Cardiology Cardiovascular system Cereals Cessation of life Computer software Confocal Microscopy Coronary Coronary Arteriosclerosis Coronary artery Detection Elements Event Exertion Frequencies Funding Grant Heart Human Image Imaging Techniques Individual Lead Lesion Life Location Magnetic Resonance Imaging Medical Modeling Necrosis Patients Prize Process Property Research Personnel Resolution Risk Risk Factors Role Rupture Sampling Sampling Studies Shapes Site Solid Solutions Spatial Distribution Staining method Stains Stress Structure System Thick Thrombosis Thrombus Tissues Vacuum Variant Water X-Ray Computed Tomography acute coronary syndrome base calcification cardiovascular risk factor college comparative effectiveness effectiveness research imaging modality in vivo innovation insight instrumentation interfacial macrophage meetings novel plaque lesion posters public health relevance symposium

项目摘要

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (05): Comparative Effectiveness Research; Challenge Topic 05-HL-104 Reducing cardiovascular risk in moderate-risk and asymptomatic patients. More than half of the 500,000 coronary artery deaths each year in the U.S. from acute coronary syndrome are due to the rupture of the thin fibrous cap overlying the necrotic core of the lesion and the formation of a thrombus. The mechanism as to why some thin caps rupture and others do not is very likely the single most important unanswered question in life threatening atherothrombotic lesions. We recently proposed a new paradigm of thin cap fibroatheroma (TCFA) rupture, suggesting that minute calcifications located in the cap itself increase tissue stress concentration and plaque vulnerability. Microcalcifications can lead to cavitation induced debonding, a process in which the tissue in the cap will pull away from the calcified inclusion and tear when tensile stress in the tissue due to blood pressure becomes too large. The first experimental evidence for this new paradigm was recently provided using confocal microscopy and high resolution micro computed tomography. In Aim 1 we will use a high resolution micro-CT imaging system to examine a much broader sample of ruptured and non-ruptured human thin cap fibroatheroma and statistically analyze the frequency, size, shape and spatial distribution of the cellular-level microcalcifications. In Aim 2 we quantitatively evaluate the impact of the microcalcifications on the biomechanical stability of the cap using a three-dimensional (3D) multi-level finite element model (FEM) of realistic 3D geometries of human coronary lesions based on high resolution micro-CT imaging. We will investigate the stress concentration effect produced by the size, shape and presence of multiple microcalcifications in close proximity within a region of high peak circumferential stress (PCS), on the biomechanics of cap rupture. This multi-level micro-CT based approach has the ability to include the fine grain structure required to imbed local solutions in the vicinity of the microinclusions, which is critical to determine the PCS amplification leading to fibroatheroma rupture. These studies, if successful, could resolve the long-standing mystery as to why some vulnerable plaque lesions are more prone to rupture than others and, as a result, provide vital new criteria for the detection and treatment of vulnerable plaque. PUBLIC HEALTH RELEVANCE: The rupture of the thin fibrous cap overlying the necrotic core of a vulnerable plaque is the principal cause of acute coronary syndrome. Unfortunately, the mechanism of vulnerable plaque rupture has remained a mystery. We proposed that the rupture of thin cap fibroatheroma may be caused by minute calcifications in the cap itself due to tissue stress concentration and provided the first experimental evidence for this new paradigm. We will investigate the impact of microcalcifications on cap rupture using a three-dimensional (3D) multi-level finite element model of realistic 3D geometries of human coronary lesions based on high resolution micro-CT imaging. If successful, this study may provide important insights on the rupture of fibrous cap atheromas responsible for more than half of the 500,000 coronary artery disease deaths in US every year.

描述（由申请人提供）：本申请解决了广泛的挑战领域（05）：比较有效性研究；挑战主题 05-HL-104 降低中危和无症状患者的心血管风险。在美国，每年因急性冠状动脉综合征导致的 50 万人冠状动脉死亡中，有一半以上是由于覆盖病变坏死核心的薄纤维帽破裂并形成血栓所致。关于为什么一些薄帽破裂而另一些不破裂的机制很可能是危及生命的动脉粥样硬化血栓病变中最重要的未解答的问题。我们最近提出了薄帽纤维粥样斑块（TCFA）破裂的新范例，表明帽本身的微小钙化增加了组织应力集中和斑块脆弱性。微钙化可导致空化引起的脱粘，在该过程中，当血压导致组织中的拉伸应力过大时，帽中的组织将从钙化夹杂物中脱离并撕裂。最近使用共焦显微镜和高分辨率显微计算机断层扫描提供了这种新范例的第一个实验证据。在目标 1 中，我们将使用高分辨率微型 CT 成像系统来检查更广泛的破裂和非破裂人类薄帽纤维粥样斑块样本，并统计分析细胞水平微钙化的频率、大小、形状和空间分布。在目标 2 中，我们使用基于高分辨率显微 CT 的人体冠状动脉病变真实 3D 几何形状的三维 (3D) 多级有限元模型 (FEM) 定量评估微钙化对冠帽生物力学稳定性的影响成像。我们将研究高峰值周向应力 (PCS) 区域内多个微钙化点的大小、形状和存在所产生的应力集中效应，对帽破裂的生物力学产生影响。这种基于多级微 CT 的方法能够包含在微包含物附近嵌入局部溶液所需的细晶结构，这对于确定导致纤维粥样斑块破裂的 PCS 放大至关重要。这些研究如果成功，可以解决长期存在的谜团，即为什么某些易损斑块病变比其他斑块更容易破裂，从而为易损斑块的检测和治疗提供重要的新标准。公众健康相关性：覆盖易损斑块坏死核心的薄纤维帽破裂是急性冠状动脉综合征的主要原因。不幸的是，易损斑块破裂的机制仍然是个谜。我们提出，薄帽纤维粥样斑块的破裂可能是由于组织应力集中导致帽本身的微小钙化引起的，并为这一新范例提供了第一个实验证据。我们将使用基于高分辨率显微 CT 成像的人体冠状动脉病变的真实 3D 几何形状的三维 (3D) 多级有限元模型来研究微钙化对冠破裂的影响。如果成功，这项研究可能会提供关于纤维帽粥样斑块破裂的重要见解，而纤维帽粥样斑块破裂导致美国每年 500,000 例冠状动脉疾病死亡，其中一半以上是由纤维帽粥样斑块破裂引起的。