Development, characterization, and curve fitting of rate-dependent models of calcified cerebral embolus analogs for acute ischemic stroke

IF 2.7 3区 医学 Q2 BIOPHYSICS
Jose L. Monclova, Daniel J. Walsh, Madelyn E. Hummel, Sophia Weatherwax, Francesco Costanzo, Scott D. Simon, Keefe B. Manning
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引用次数: 0

Abstract

Acute ischemic stroke (AIS) is a leading cause of death worldwide. In recent years, several studies have characterized the material properties of clot types that were removed from stroke patients, showing a highly nonlinear, asymmetric behavior in compression and tension. However, little is still known about the clot phenotype underlying complications in endovascular thrombectomy (EVT). In this study, we propose a spectrum of clot surrogates for highly stiff, red blood cell-rich, aged, calcified clots that may underpin the outcomes of AIS procedures, often called ‘hyperdense middle cerebral artery signs’ by clinicians. This study aims to characterize the high-strain, rate-dependent mechanical properties of a broad range of aged and calcified clot analogs. Blood from healthy donors was used to form aged and calcified clots, which were subjected to rate-dependent uniaxial testing and structural analyses. A method for curve fitting standard linear solids with multiple hyperelastic elements is considered, and a subsequent procedure is outlined for fitting rate-dependent data. High-strain clot analog peak stresses and moduli are on the same order of magnitude as previous studies, with the hypercalcified clots nearly an order of magnitude stiffer than previously recorded. The calcification was shown to be time dependent, as the longer the clots incubated in the calcium solutions, the stiffer they became. SEM images show drastic changes in clot morphology, with mineral nucleation evident around all components of the clot. The curve fitting produced parameters for a host of models that can be used in numerical implementation. The authors note that when curve fitting, energy state of the system should be taken into consideration, in addition to the minimization of the relative error. We demonstrate a wide spectrum of clot properties that are captured well by rate-dependent models for the full dataset, the compressive data, and the tensile data. In this study, we provide a method for creating and characterizing hypercalcified clot analogs as surrogates for the clot phenotype underlying EVT complications. The library of clot properties reported here can be used in numerical simulations, with careful considerations of the curve fitting methods that are employed. These data highlight the need for further investigation into this clot phenotype, which may be related to the subset of AIS patients where clots are unable to be removed.

急性缺血性中风钙化脑栓塞类似物的发生率依赖模型的发展、表征和曲线拟合。
急性缺血性中风(AIS)是世界范围内的主要死亡原因。近年来,一些研究描述了从中风患者身上移除的血块类型的材料特性,显示出高度非线性、不对称的压缩和张力行为。然而,对于血管内血栓切除术(EVT)中潜在并发症的血块表型知之甚少。在这项研究中,我们提出了一种高硬度、红细胞丰富、老化、钙化的凝块替代物,这些凝块可能是AIS手术结果的基础,临床医生通常称之为“大脑中动脉高密度征象”。本研究的目的是表征高应变,速率依赖的机械性能的广泛老化和钙化凝块类似物。来自健康献血者的血液被用来形成老化和钙化的血块,并对其进行率相关的单轴测试和结构分析。考虑了一种具有多个超弹性单元的标准线性固体曲线拟合方法,并概述了拟合速率相关数据的后续程序。高应变凝块模拟峰值应力和模量与以前的研究在同一个数量级上,高钙化凝块几乎比以前记录的硬一个数量级。钙化与时间有关,因为凝块在钙溶液中培养的时间越长,它们就变得越硬。扫描电镜图像显示了血块形态的剧烈变化,在血块的所有成分周围都有明显的矿物成核。曲线拟合产生了一系列可用于数值实现的模型参数。作者指出,在拟合曲线时,除了考虑相对误差的最小化外,还应考虑系统的能量状态。我们展示了广泛的凝块特性,通过速率相关模型可以很好地捕获完整数据集、压缩数据和拉伸数据。在这项研究中,我们提供了一种方法来创建和表征高钙化凝块类似物,作为EVT并发症的凝块表型的替代品。这里报告的凝块属性库可以用于数值模拟,并仔细考虑所采用的曲线拟合方法。这些数据强调了对这种血块表型进行进一步研究的必要性,这可能与血块无法清除的AIS患者亚群有关。
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来源期刊
Biomechanics and Modeling in Mechanobiology
Biomechanics and Modeling in Mechanobiology 工程技术-工程:生物医学
CiteScore
7.10
自引率
8.60%
发文量
119
审稿时长
6 months
期刊介绍: Mechanics regulates biological processes at the molecular, cellular, tissue, organ, and organism levels. A goal of this journal is to promote basic and applied research that integrates the expanding knowledge-bases in the allied fields of biomechanics and mechanobiology. Approaches may be experimental, theoretical, or computational; they may address phenomena at the nano, micro, or macrolevels. Of particular interest are investigations that (1) quantify the mechanical environment in which cells and matrix function in health, disease, or injury, (2) identify and quantify mechanosensitive responses and their mechanisms, (3) detail inter-relations between mechanics and biological processes such as growth, remodeling, adaptation, and repair, and (4) report discoveries that advance therapeutic and diagnostic procedures. Especially encouraged are analytical and computational models based on solid mechanics, fluid mechanics, or thermomechanics, and their interactions; also encouraged are reports of new experimental methods that expand measurement capabilities and new mathematical methods that facilitate analysis.
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