Biomechanical Indices for Coronary Lesion Rupture Risk and Lesion Prognostication

项目摘要 急性冠状动脉综合征（ACS）是突然的管腔血栓形成的结果。这些病理事件是 严重的临床问题，不仅是因为它们的频率，而且还由于诊断的挑战， 对冠状动脉病变的风险进行分层（即，稳定与破裂倾向），并确定将经历 快速发展和脆弱性增加（即，病灶切除）。虽然侵入性成像方式 可以表征斑块组成和表型，使用成像对冠状动脉病变进行风险分层， 导致急性冠脉综合征的说法不太准确因此，斑块风险分层策略应 超越基于图像的形态学标记，并专注于识别 导致冠状动脉疾病（CAD）快速进展，增加脆弱性和破裂风险。的 因此，R 01提案的总体目标是检验损伤的力学指标的预测价值 在评价冠状动脉自然史的前瞻性研究中进行危险分层和验证 动脉粥样硬化我们的中心假设是，机械指数将促进高风险的识别 冠状动脉病变并提高预测斑块破裂的能力。为了实现这一目标，我们将 通过两个假设驱动的特定目的进行研究：（i）检查斑块材料的预测价值 硬度在分层冠状动脉病变破裂的风险和（ii）评估变形的预后价值- 诱导的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 开发并验证计算框架，以提取冠状动脉的异质材料特性 并通过前向有限差分法预测3D患者特定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，以确定其临床价值。 成功完成拟议的研究将促进对预后价值的理解， CAD自然史中的机制，并推进患者管理和治疗策略， 尽量减少ACS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.