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

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.