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

Purpose: 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 ‘hyper-dense middle cerebral artery signs’ by clinicians. Methods: 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. Results: 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 not 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. Conclusion: 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.

Citation

Manning, Keefe; Costanzo, Francesco; Monclova, Jose; Simon, Scott; Walsh, Daniel ; Hummel, Madelyn; Weatherwax, Sophia (2024). DATA: Development, characterization, and curve fitting of rate dependent models of calcified cerebral embolus analogs for acute ischemic stroke [Data set]. Scholarsphere. https://doi.org/10.26207/w7s8-gx26

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Work Title DATA: Development, characterization, and curve fitting of rate dependent models of calcified cerebral embolus analogs for acute ischemic stroke
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Open Access
Creators
  1. Keefe B Manning
  2. Francesco Costanzo
  3. Jose Monclova
  4. Scott Simon
  5. Daniel Walsh
  6. Madelyn Hummel
  7. Sophia Weatherwax
Keyword
  1. calcified
  2. clots
  3. curve fits
License CC0 1.0 (Public Domain Dedication)
Work Type Dataset
Acknowledgments
  1. This work was supported, in part by funding from the United States National Institutes of Health (NHLBI) through NIH Grant HL146921, US NIH (NIGMS) T32 Physiological Adaptations to Stress Grant T32GM108563, the Penn State Clinical Research Center in the Clinical and Translational Science Institute, the Penn State Huck Institutes’ Microscopy Core Facility (RRID: SCR_024457), an Alfred P. Sloan Scholarship and a Gates Millennium Scholarship.
Publication Date January 7, 2024
DOI doi:10.26207/w7s8-gx26
Deposited January 06, 2025

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Version 1
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  • Created
  • Updated
  • Updated Keyword, Description, Publication Date Show Changes
    Keyword
    • calcified, clots, curve fits
    Description
    • Purpose: 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 ‘hyper-dense middle cerebral artery signs’ by clinicians.
    • Methods: 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.
    • Results: 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 not 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.
    • Conclusion: 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.
    Publication Date
    • 2024-01-07
  • Updated Acknowledgments Show Changes
    Acknowledgments
    • This work was supported, in part by funding from the United States National Institutes of Health (NHLBI) through NIH Grant HL146921, US NIH (NIGMS) T32 Physiological Adaptations to Stress Grant T32GM108563, the Penn State Clinical Research Center in the Clinical and Translational Science Institute, the Penn State Huck Institutes’ Microscopy Core Facility (RRID: SCR_024457), an Alfred P. Sloan Scholarship and a Gates Millennium Scholarship.
  • Added Creator Keefe B Manning
  • Added Creator Francesco Costanzo
  • Added Creator Jose Monclova
  • Added README.txt
  • Added Excel Data.zip
  • Added Mathematica Curve Fits.zip
  • Added Compressive Data.zip
  • Added Tensile Data.zip
  • Deleted Creator Jose Monclova
  • Added Creator Jose Monclova
  • Added Creator Scott Simon
  • Added Creator Daniel Walsh
  • Added Creator Madelyn Hummel
  • Added Creator Sophia Weatherwax
  • Updated License Show Changes
    License
    • http://creativecommons.org/publicdomain/zero/1.0/
  • Published
  • Updated