CRCNS: Modeling for Carotid Plaque Rupture and Stroke

描述（由申请人提供）：中风是美国第三大死亡原因，通常由动脉粥样硬化性颈动脉斑块破裂引起。中风可能导致各种脑损伤、脑功能障碍和残疾。大量表面上健康的受害者突然死亡，之前没有任何症状。现有的筛查和诊断方法不足以在事件发生前识别受害者。本项目的目标是将计算建模、磁共振成像（MRI）技术、超声/多普勒技术（US）、力学测试和病理分析相结合，对颈动脉粥样硬化斑块进行定量力学分析，量化可能发生斑块破裂的临界血流量和斑块应力/应变条件；并寻求将定量力学分析与最先进的成像技术相结合的潜力，以实现更好的筛查和诊断应用。这些目标与NIBIB的使命相一致。40名计划接受颈动脉内膜切除术的患者将被招募参加本研究，并获得适当的同意。另外50个尸体或离体动脉内膜切除术颈动脉斑块样本也将用于研究。具体目标是：(1)开发和整合3D MRI、美国技术和计算方法，量化斑块结构和血管材料特性；(2)基于MRI、US技术和术中测量获得的体外、离体和体内测量数据，建立血管相互作用的三维多组分计算模型；(3)对动脉粥样硬化斑块进行完整的力学分析，确定临界应力/应变条件与斑块形态和组成、血管力学性能和血流压力条件之间的相关性；(4)量化和验证临界应力/应变条件与斑块易损性之间的相关性，确定医生可用于临床和诊断决策的临界应力/应变指标。这将为未来的软件开发和技术集成奠定基础。通过大规模的患者研究验证，长期目标是将计算建模与MRI和US成像技术相结合，可以更好地解释MRI和超声图像中已经包含的信息，开发新的成像软件，更准确地评估斑块易损，并对可能的中风进行潜在的早期预测。随着预测准确性的提高，某些不必要的手术可以避免，医疗费用可以降低，一些致命事件可以预防。综合计算力学图像分析改进了当前的图像分析技术，可以为涉及多组分相互作用的复杂生物结构的许多进一步研究活动提供基础。

DESCRIPTION (provided by applicant): Stroke is the third leading cause of death in the United States which is often caused by atherosclerotic carotid plaque rupture. Stroke may lead to various brain damages, brain malfunctions and disability. A large number of victims who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The objectives of this project are to integrate computational modeling, Magnetic Resonance Imaging (MRI) technology, ultrasound/Doppler technology (US), mechanical testing, and pathological analysis to perform quantitative mechanical analysis to atherosclerotic carotid plaques, to quantify critical blood flow and plaque stress/strain conditions under which plaque rupture is likely to occur, and to seek the potential that quantitative mechanical analysis can be integrated into state-of-the-art imaging technologies for better screening and diagnostic applications. Those objectives are consistent with the mission of the NIBIB. Forty patients scheduled to undergo carotid endarterectomy will be recruited to participate in this study with proper consent. Fifty additional cadaveric or ex-vivo endarterectomy carotid plaque samples will also be used in the study. The specific aims are: (1) Develop and integrate 3D MRI, US technologies and computational methods to quantify plaque structure and vessel material properties; (2) Develop 3D multi-component computational models with blood- vessel interactions based on in vitro, ex vivo and in vivo measurements obtained by MRI, US technologies and intra- operative measurements; (3) Perform complete mechanical analysis for atherosclerotic plaques and identify correlations between critical stress/strain conditions and plaque morphology and composition, vessel mechanical properties and blood flow pressure conditions; (4) Quantify and validate correlations between critical stress/strain conditions and plaque vulnerability and identify critical stress/strain indicators which could be used by doctors to make clinical and diagnostic decisions. This will establish the base for future software development and technology integration. With large-scale patient study validations, the long term goal is to establish that integration of computational modeling with MRI and US imaging technologies can lead to better interpretation of the information already contained in MRI and ultrasound images, new development of imaging software for more accurate assessment of plaque vulnerability, and potential early prediction of possible stroke. With improved accuracy of predictions, certain unnecessary operations may be avoided, cost of medical care can be reduced, and some fatal events may be prevented. The integrated computational mechanical image analysis improves current image analysis techniques and can serve as basis for many further research activities involving complex biological structures with multi-component interactions.