Summary

基于光学相干断层扫描的冠状动脉粥样硬化进展生物力学流固相互作用分析

Published: January 15, 2022
doi:

Summary

需要确定哪些动脉粥样硬化病变将在冠状动脉脉管系统中进展,以指导心肌梗死发生前的干预。本文概述了在商业有限元求解器中使用流固耦合技术从光学相干断层扫描中对动脉进行生物力学建模,以帮助预测这一进展。

Abstract

在本文中,我们提出了冠状动脉脉管系统中动脉粥样硬化斑块生物力学分析的完整工作流程。由于动脉粥样硬化是全球死亡,发病率和经济负担的主要原因之一,因此需要新的方法来分析和预测其进展。一种这样的计算方法是使用流固耦合(FSI)来分析血流和动脉/斑块结构域之间的相互作用。结合 体内 成像,这种方法可以针对每个患者量身定制,有助于区分稳定和不稳定的斑块。我们概述了三维重建过程,利用血管内光学相干断层扫描(OCT)和侵入性冠状动脉造影(ICA)。在商业有限元求解器中进行设置和分析之前,将讨论仿真的边界条件的提取,包括复制动脉的三维运动。概述了描述动脉壁的高度非线性超弹性特性和脉动血流速度/压力的过程,以及建立两个域之间的系统耦合。我们通过分析心肌梗死后患者的非罪魁祸首,轻度狭窄,富含脂质的斑块来证明该程序。讨论了与动脉粥样硬化斑块进展相关的已建立和新出现的标志物,例如壁剪切应力和局部归一化螺旋度,并且与动脉壁和斑块的结构反应相关。最后,我们将结果转化为潜在的临床相关性,讨论局限性,并概述进一步发展的领域。本文中描述的方法有望帮助确定有动脉粥样硬化进展风险的部位,因此可以帮助管理动脉粥样硬化的重大死亡,发病率和经济负担。

Introduction

冠状动脉疾病(CAD)是最常见的心脏病类型,也是全球死亡和经济负担的主要原因之一1,2。在美国,大约每八例死亡中就有一例归因于加元3,4,而全球大多数加拿大元死亡现在见于低收入和中等收入国家5。动脉粥样硬化是这些死亡的主要驱动因素,斑块破裂或糜烂导致冠状动脉闭塞和急性心肌梗死(AMI)6。即使在罪魁祸首冠状动脉病变的血运重建后,患者在AMI后仍有复发性重大不良心血管事件(MACE)的风险,这主要是由于同时存在其他非罪魁祸首斑块,这些斑块也容易破裂7。冠状动脉内成像提供了检测这些高风险斑块的机会8。尽管血管内超声 (IVUS) 是评估斑块体积的金标准,但与光学相干断层扫描 (OCT) 的高分辨率 (10-20 μm) 相比,其识别脆弱斑块的微观结构特征的分辨率有限。在大型脂质池上覆盖的薄而发炎的纤维帽已被证明是脆弱斑块9的最重要特征,并且在目前可用的冠状动脉内成像方式中,OCT最好地识别和测量10。重要的是,OCT还能够评估其他高风险斑块特征,包括:脂质弧;巨噬细胞浸润;存在薄帽纤维粥样硬化(TCFA),其定义为富含脂质的核心,具有覆盖的薄纤维帽(<65μm);斑点钙化;和斑块微通道。在AMI后,在非罪魁祸首斑块中检测到这些高风险特征与未来MACE11的风险增加多达6倍有关。然而,尽管如此,血管造影和OCT成像预测哪些冠状动脉斑块将进展并最终破裂或侵蚀的能力是有限的,阳性预测值仅为20%-30%8 。这种有限的预测能力阻碍了临床决策,围绕哪些非罪魁祸首斑块进行治疗(例如,通过支架置入术)7,12。

除了患者因素和斑块的生物学特征外,冠状动脉中的生物力学力也是斑块进展和不稳定性的重要决定因素13。一种有望帮助全面评估这些力的技术是流固耦合(FSI)14 仿真。壁剪切应力(WSS),也称为内皮剪切应力,一直是冠状动脉生物力学研究的传统焦点15,人们普遍认为WSS在动脉粥样硬化形成中起病因作用16。主要使用计算流体动力学(CFD)技术模拟,低WSS区域与内膜增厚17,血管重塑18 以及预测病变进展19 和未来MACE20有关。这些分析的最新进展表明,WSS矢量场拓扑21及其多向特征22比单独使用WSS幅度更能预测动脉粥样硬化风险。然而,WSS只能捕捉到腔壁处整体生物力学系统的一瞥,并且与成像方式非常相似,没有一个生物力学指标可以可靠地识别高风险的动脉粥样硬化特征。

进一步的指标在动脉粥样硬化的形成中变得具有潜在的重要性。腔内流动特征23就是这样一个例子,螺旋流,通过各种指标24量化,表明通过抑制扰动的流动模式25,26起到动脉粥样硬化保护作用。虽然CFD技术可以分析这些流动特征并提出广泛的有用结果,但它们没有考虑血流,动脉结构和一般心脏运动之间的潜在相互作用。这种将动态系统简化为刚性壁的做法错过了潜在的关键结果,例如纤维帽应力。虽然支持和反对FSI对CFD需求的争论仍在继续27,28,29,但许多比较忽略了包括心室功能的影响。这种限制可以通过FSI克服,FSI已经表明,通过心室功能的影响对动脉施加的动态弯曲和压缩可以显着影响斑块和动脉结构应力以及流量指标,如WSS 30,31,32。这很重要,因为结构应力也是分析和预测斑块破裂33,34的关键指标并且已被建议与斑块增加的区域14,35共同定位。捕获这些相互作用可以更真实地表示冠状动脉环境和疾病进展的潜在机制。

为了解决这个问题,我们概述了从OCT成像36 开发患者特定几何体的过程,以及使用商业有限元求解器设置和运行动脉FSI仿真的过程。在对患者动脉进行三维计算重建之前,详细介绍了手动提取腔,脂质和外动脉壁的过程。我们概述了模拟设置,偶联和比较基线的过程,以及随访的OCT成像参数,以确定病变进展。最后,我们讨论了数值结果的后处理,以及这些数据如何通过比较生物力学结果与病变进展/消退来具有临床相关性。总体方法见于一名 58 岁高加索男性患者的右冠状动脉 (RCA) 非罪魁祸首、轻度狭窄、富含脂质的斑块,该患者在高血压、2 型糖尿病、肥胖 (BMI 32.6) 和早产 CAD 家族史的情况下出现急性非 ST 段抬高型心肌梗死。 然后在12个月后作为正在进行的临床试验的一部分(COCOMO-ACS试验ACTRN12618000809235)。我们预计这种技术可以进一步完善,并用于识别具有高进展风险的冠状动脉斑块。

Protocol

从招募到正在进行的COCOMO-ACS随机对照试验(ACTRN12618000809235;皇家阿德莱德医院HREC参考编号:HREC/17/RAH/366),并由中央阿德莱德地方卫生网络(CALHN)研究服务授予额外的伦理学批准,用于生物力学模拟(CALHN参考编号14179)。 图 1 总结了以下协议中概述的完整工作流,可应用于任何支持 FSI 的软件或代码。 1. 图像评估 使用解剖学标志…

Representative Results

对于动脉粥样硬化进展的已建立和新出现的生物力学标志物,提出了具有代表性的结果。 图 10显示了 WSS 和 WSS 派生结果等既定指标(包括时间平均壁剪切应力 (TAWSS) 和振荡剪切指数 (OSI))。心脏周期的壁剪切应力主要由血流速度驱动,然而,动脉几何形状及其运动/收缩在其空间分布中起着重要作用。这可以在TAWSS和OSI轮廓中看到,OSI是血流再循环的一种测量方法,与…

Discussion

从数值建模和临床结果方面来看,使用FSI方法分析冠状动脉生物力学仍然是一个发展中的领域。在这里,我们描述了利用OCT和血管造影成像,基于有限元/有限体积方法建立患者特定FSI分析的大纲。虽然我们在这里描述的方法使用商业有限元求解器,但该程序可以应用于任何支持FSI的软件。该方法仍有一些限制需要改进。首先,我们承认仅为单个患者提供代表性结果的局限性;然而,我们提出了当?…

Divulgations

The authors have nothing to disclose.

Acknowledgements

作者要感谢阿德莱德大学,皇家阿德莱德医院(RAH)和南澳大利亚健康与医学研究所(SAHMRI)提供的支持。COCOMO-ACS试验是一项由研究者发起的研究,由澳大利亚国家卫生和医学研究委员会(NHMRC)(ID1127159)和澳大利亚国家心脏基金会(ID101370)的项目资助资助。H.J.C.由西太平洋大学学者信托基金(未来领袖奖学金)的奖学金支持,并得到阿德莱德大学机械工程学院和教育,技能和就业研究培训计划(RTP)奖学金的支持。S.J.N.获得NHMRC的首席研究奖学金(ID1111630)。P.J.P.获得澳大利亚国家心脏基金会(FLF102056)的2级未来领袖奖学金和NHMRC(CDF1161506)的2级职业发展奖学金。

Materials

ANSYS Workbench (version 19.0) ANSYS Commercial finite element solver
MATLAB (version 2019b) Mathworks Commercial programming platform
MicroDicom/ImageJ MicroDicom/ImageJ Open Source DICOM reader
Visual Studio (version 2019) Microsoft Commercial Integrated Development Environment

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Carpenter, H. J., Ghayesh, M. H., Zander, A. C., Ottaway, J. L., Di Giovanni, G., Nicholls, S. J., Psaltis, P. J. Optical Coherence Tomography Based Biomechanical Fluid-Structure Interaction Analysis of Coronary Atherosclerosis Progression. J. Vis. Exp. (179), e62933, doi:10.3791/62933 (2022).

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