Jose L. Monclova, Daniel J. Walsh, Madelyn E. Hummel, Sophia Weatherwax, Francesco Costanzo, Scott D. Simon, Keefe B. Manning
{"title":"Development, characterization, and curve fitting of rate-dependent models of calcified cerebral embolus analogs for acute ischemic stroke","authors":"Jose L. Monclova, Daniel J. Walsh, Madelyn E. Hummel, Sophia Weatherwax, Francesco Costanzo, Scott D. Simon, Keefe B. Manning","doi":"10.1007/s10237-025-01997-w","DOIUrl":null,"url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":489,"journal":{"name":"Biomechanics and Modeling in Mechanobiology","volume":"24 5","pages":"1855 - 1874"},"PeriodicalIF":2.7000,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12375946/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomechanics and Modeling in Mechanobiology","FirstCategoryId":"5","ListUrlMain":"https://link.springer.com/article/10.1007/s10237-025-01997-w","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOPHYSICS","Score":null,"Total":0}
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.
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.