Biomechanical Indices for Coronary Lesion Rupture Risk and Lesion Prognostication

项目总结 急性冠脉综合征(ACS)是突然的管腔血栓形成的结果。这些病理事件是一种 严重的临床问题，不仅是因为它们的频率，而且是因为 对冠状动脉病变的风险进行分层(即稳定性和易破裂)，并识别将要经历的病变 进展迅速，易损性增加(即病变预测)。尽管有侵入性的成像方式 可以表征斑块的成分和表型，利用成像来对冠状动脉病变进行风险分层 事实证明，沉淀ACS事件的准确性较低。因此，斑块风险分层策略应该 超越基于图像的形态标记，专注于识别局部环境因素(S) 会导致冠状动脉疾病(CAD)的快速发展、脆弱性增加和破裂风险。这个 因此，R01提案的总体目标是检查机械指标对病变的预测价值 评价冠状动脉自然病史的前瞻性研究中的风险分层和预测 动脉硬化。我们的中心假设是机械指数将促进高风险的识别 冠状动脉病变和促进预测斑块破裂的能力。为了实现这一目标，我们将采取以下做法 通过两个假设驱动的特定目标进行研究：(I)检查斑块材料的预测价值 硬性分层冠状动脉病变破裂的风险和(Ii)评估变形的预后价值-- 诱发壁应力用于识别快速进展的CAD和增加的斑块易损性。我们建议 开发和验证计算框架以提取冠状动脉的非均质材料属性 通过前向有限元方法预测3D患者特有的冠状动脉斑块力学环境 元素分析。随后，这些框架将被临床翻译，以确定它们的临床价值。 拟议研究的成功完成将促进对高血压的预后价值的理解。 CAD自然历史中的力学和先进的患者管理和治疗策略 最大限度减少与急性冠脉综合征相关的不良事件。

PROJECT SUMMARY Acute coronary syndromes (ACS) are a result of sudden luminal thrombosis. These pathologic events are a significant clinical problem, not only because of their frequency, but also due to the diagnostic challenge in stratifying risk for coronary lesions (i.e., stable versus rupture-prone) and identifying lesions that will undergo rapid progression and increased vulnerability (i.e., lesion prognostication). Although invasive imaging modalities can characterize plaque composition and phenotype, the use of imaging to risk stratify coronary lesions that will precipitate an ACS event has proven less accurate. Thus, plaque risk stratification strategies should move beyond image-based morphologic markers and focus on identifying the local environmental factor(s) that contribute to rapid coronary artery disease (CAD) progression, heightened vulnerability, and rupture risk. The overall goal of this R01 proposal, therefore, is to examine the predictive value of mechanical metrics for lesion risk stratification and prognostication in prospective studies evaluating the natural history of coronary atherosclerosis. Our central hypothesis is that mechanical indices will advance the identification of high-risk coronary lesions and promote the ability to predict plaque rupture. To realize this goal, we will approach this research through two hypothesis-driven Specific Aims: (i) examine the predictive value of plaque material stiffness in stratifying risk for coronary lesion rupture and (ii) evaluate the prognostic value of deformation- induced wall stress for identifying rapidly progressing CAD and increased plaque vulnerability. We propose to develop and validate computational frameworks to extract the heterogeneous material properties of coronary arteries and predict the 3D patient-specific coronary plaque mechanical environment through forward finite element analysis. Subsequently, these frameworks will be clinically translated to establish their clinical value. Successful completion of the proposed research will advance understanding of the prognostic value of mechanics in the natural history of CAD and advance patient management and treatment strategies towards minimizing adverse events associated with ACS.