In Vivo IVUS Image-Based Modeling for Human Coronary Plaque Assessment

描述（由申请人提供）：本项目的目的是将各向异性计算建模与体内血管内超声（IVUS）、血管造影术、离体磁共振成像（MRI）、机械测试和病理组织学分析相结合，以分析易损性动脉粥样硬化冠状动脉斑块，并确定关键血流和斑块应力/应变指标，用于定量冠状动脉斑块易损性评估。长期目标是：a）开发计算机械图像分析工具，用于更准确的斑块评估和对当前美国心脏协会（AHA）斑块分类方案的可能的定量改进; B）识别临界流动和应力/应变斑块易损性风险指标，其可以被监测用于相关心血管疾病的早期预测、诊断、治疗和预防。假设是：（1）临界斑块应力/应变条件与斑块易损性密切相关，可用作进一步区分AHA高级斑块分类中的斑块的指标（V-VIII型），并提供更定量的方法来评估斑块破裂风险;（2）结合体内IVUS成像，压力和流量测量以及具有流体-结构相互作用（FSI）的3D各向异性多组分模型循环弯曲将提高冠状动脉斑块的力学分析的准确性，并导致更准确的体内斑块易损性评估。该项目有四个具体目标。目标1：开发并整合体内IVUS成像、流量和压力测量技术、血管造影术、多对比离体MRI、组织学分析和双轴机械测试技术，以量化斑块形态、组织成分、曲率、病变部位的冠状动脉内流量和压力条件以及各向异性血管材料特性。目标二：建立100个人体冠状动脉斑块的三维各向异性多组分FSI模型（50例体内IVUS，50例离体MRI），循环弯曲和冠状动脉内血流和压力条件（仅IVUS）以获得3D血流剪切应力和斑块应力/应变数据;目的3：对冠状动脉斑块进行3D机械图像分析，并确定临界应力/应变条件之间的相关性（潜在风险指标）和斑块形态和组成、血管机械性能和血流压力条件（患者数据）。计算模型将通过体内IVUS和体外实验数据进行验证。目标4：介绍定量体内/离体/组织学斑块易损性评估方案，并与AHA基于组织学的斑块分类进行比较，以了解AHA方案和潜在筛查实践的可能定量改进。该项目的成功将导致更准确的斑块脆弱性评估和对可能的斑块破裂风险的预测，从而可以做出更好的治疗决策，从而改善公共卫生并降低医疗保险的成本。机械图像分析和软件添加，以增强MRI/IVUS成像技术的临床应用是可能的，与未来的大规模患者研究确认。 公共卫生相关性：许多心血管事件（如心脏病发作和中风）是由动脉粥样硬化斑块破裂引起的，可能会在没有任何警告信号的情况下发生。该项目的成功将导致更准确的体内冠状动脉斑块脆弱性评估和预测可能的斑块破裂风险，以便更好和及时地做出治疗决定，从而改善公共卫生并降低医疗保险成本。随着模型构建和数据分析程序的自动化，研究成果的商业化成为可能。

DESCRIPTION (provided by applicant): The objective of this project is to combine anisotropic computational modeling with in vivo intravascular ultrasound (IVUS), angiography, ex vivo Magnetic Resonance Imaging (MRI), mechanical testing, and pathohistological analysis to analyze vulnerable atherosclerotic coronary plaques and identify critical blood flow and plaque stress/strain indicators for quantitative coronary plaque vulnerability assessment. The long term goals are: a) develop computational mechanical image analysis tools for more accurate plaque assessment and possible quantitative improvement to the current American Heart Association (AHA) plaque classification scheme; b) identify critical flow and stress/strain plaque vulnerability risk indicators which could be monitored for early prediction, diagnosis, treatment, and prevention of related cardiovascular diseases. The hypotheses are: (1) Critical plaque stress/strain conditions correlate closely with plaque vulnerability and may be used as indicators to further differentiate plaques within AHA advanced plaque classifications (types V- VIII) and provide more quantitative methods to assess plaque rupture risk; (2) Combination of in vivo IVUS imaging, pressure and flow measurements and 3D anisotropic multi-component models with fluid-structure interactions (FSI) and cyclic bending will improve the accuracy of mechanical analysis for coronary plaques and lead to more accurate in vivo plaque vulnerability assessment. This project has four specific aims. Aim 1: Develop and integrate in vivo IVUS imaging, flow and pressure measurements techniques, angiography, multi-contrast ex vivo MRI, histological analysis, and biaxial mechanical testing techniques to quantify plaque morphology, tissue components, curvature, intra-coronary flow and pressure conditions at the lesion site, and anisotropic vessel material properties. Aim 2: Develop 3D anisotropic multi-component FSI models for 100 human coronary plaques (50 in vivo IVUS, 50 ex vivo MRI) with cyclic bending and intra-coronary flow and pressure conditions (IVUS only) to obtain 3D flow shear stress and plaque stress/strain data; Aim 3: perform 3D mechanical image analysis for coronary plaques and identify correlations between critical stress/strain conditions (potential risk indicators) and plaque morphology and composition, vessel mechanical properties and blood flow pressure conditions (patient data). Computational models will be validated by both in vivo IVUS and in vitro experimental data. Aim 4: Introduce quantitative in vivo/ex vivo/histological plaque vulnerability assessment schemes and compare with AHA histology-based plaque classifications for possible quantitative improvements on AHA scheme and potential screening practice. Success of this project will lead to more accurate plaque vulnerability assessment and predictions for possible plaque rupture risk so that better decisions for treatment can be made leading to better public health and reduced costs of Medicare. Mechanical image analysis and software additions to enhance MRI/IVUS imaging technology for clinical applications are possible with future large-scale patient study validations. PUBLIC HEALTH RELEVANCE: Many cardiovascular events (such as heart attack and stroke) are caused by atherosclerotic plaque rupture which may happen without any warning signals. Success of this project will lead to more accurate in vivo coronary plaque vulnerability assessment and predictions for possible plaque rupture risk so that better and timely decisions for treatment can be made leading to better public health and reduced costs of Medicare. Commercialization of the research results is possible with the automation of model construction and data analysis procedures.