Background: Ischemic stroke remains a major global health threat and a leading cause of mortality. Although advancements have been made in acute ischemic stroke treatment, challenges persist in achieving efficient recanalization and improved outcomes. Research on the mechanical characterization of ex vivo thrombi is limited. This paper aims to investigate the compositional and mechanical characterization of acute ischemic stroke thrombi retrieved in a per pass method and determine the relationship between composition and mechanical properties.
Methods: Thrombi fragments were collected per pass and segmented into samples. Larger fragments were sectioned into 1 mm pieces for cyclic unconfined compression testing, assessing hysteresis and tangent modulus as a measure of stiffness. The remaining pieces post-sectioning were combined into a single offcut sample, while smaller fragments were labeled as extra samples and kept for histology. Following mechanical testing, compositional analyses quantified the percentages of red blood cells, fibrin, and platelets in each sample.
Results: In 34 passes, a total of 108 thrombus fragments from 20 patients were successfully retrieved. Compositional heterogeneity was observed both between patients and within a single patient. Higher red blood cells (RBC) and lower fibrin/platelet contents were associated with Pass 1. The results showed a mean hysteresis area of 1.6 kPa and a mean hysteresis ratio of 37%. The median low strain stiffness was 1.76 kPa and the median high strain stiffness was 576.4 kPa. RBC and fibrin/platelets concentration had a linear relationship with high strain stiffness. Low strain stiffness, hysteresis area, and ratio changed with varying quantities of fibrin/platelets, RBC, and platelets composition.
Conclusion: This study enhances understanding of the relationship between thrombus composition and mechanical properties. The findings highlight the significant heterogeneity in thrombi and the non-linear viscoelastic behavior. Stiffness is highly corelated to strain levels, and the hysteresis amount depends on structural changes and varying compositional concentrations.

Introduction: Atherosclerosis is characterised by the buildup of plaque within the arterial wall and it is often the underlying cause effect of deaths related to cardiovascular diseases. Thin cap fibroatheromas are plaques with a high risk of causing clinical events due to rupture and espousal of thrombogenic components to the bloodstream. The rupture of the plaque is not yet fully understood and for this reason, tissue engineered plaques were created in a previous study to assess the rupture of the plaques based on the displacement field registered with Digital Image Correlation during a uniaxial tensile experiment. The knowledge of the material properties of the tissue-engineered fibrous cap structures makes it possible to link deformations to external loads and contributes to the understanding of plaque rupture. The study aims to create a pipeline for local mechanical property characterisation of tissue engineered fibrous plaque structures.
Methods: In this novel method inverse Finite Element Method (iFEM) was combined with the Differential Evolution machine learning algorithm to assess global and local mechanical properties of tissue engineered fibrous plaque structures. The method required three main steps. Step one was the implementation of the uniaxial tensile test into a computational model using ABAQUS version 2016 Finite Element Method (FEM) software. To couple loads and deformations the hyperelastic reduced polynomial function of second order was implemented in the FEM. The characterisation of the c10 [kPa] and c_20 [kPa] parameters in the model is the main focus of this study. After the creation of the FEM, the computed displacement field and the previously registered DIC displacement field were implemented into the iFEM pipeline. Preliminary to the experimental data study, the pipeline was tested on a synthetically generated displacement field, in order to investigate the expected accuracy of the method. In step two the global mechanical properties of the fibrous plaque structures were investigated, using the assumption of homogeneous material property distribution in the samples. The resulting material properties after the global estimation served as an initial guess for the local estimation procedure. In step three the local material properties were investigated by creating sections with independently variable material properties, thus introducing heterogeneous distribution of material properties within the samples.
Results: The global mechanical property assessment was carried out successfully and the resulting material properties are within the range of previously reported stiffness values of plaques with a similar composition. Local mechanical properties were characterised using up to twelve independently variable material parameters to investigate the heterogeneous mechanical behaviour of the constructs.
Conclusion: During this project a new method was established to assess the local mechanical properties of tissue engineered fibrous cap structures. The pipeline shows high potential to be useful when investigating plaque rupture in a controlled environment using tissue engineered constructs. The knowledge of local material properties in combination with local deformations is a great addition to the understanding of plaque rupture.

Background: The efficacy of a thrombectomy procedure for acute ischaemic stroke (AIS) is largely dependent on mechanical behaviour of thrombi and interactions with the thrombectomy device. Studies have examined clot analogues and evidence suggests that thrombus mechanical properties largely depend on composition, yet evidence based on thrombi retrieved from AIS patients is still lacking. Therefore, this study aims to characterize the mechanical properties of thrombi retrieved from AIS patients and to determine the relation to thrombus composition. Additionally, results were compared to literature in order to assess clot analogue representativeness.Methods: Directly following a thrombectomy procedure, unconfined compression tests were performed on thrombi retrieved from acute ischaemic stroke patients. For all tested samples, the material properties were characterized and related to the histologically determined composition. Identified histological components were 1) Fibrin & platelets, 2) Red blood cell and 3) Leukocytes. A subgroup analysis was performed to compare values with literature, where samples were stratified into four groups based on fibrin & platelet content (F&P -low, -moderate low, -moderate high and -high). Results: A total of 18 patients yielded 39 samples which were successfully tested and histologically analysed. Sample stiffness was found to be positively correlated to fibrin & platelet content (Rs=0.69, p<0.001). A good histological distribution was present within the data, as the fibrin & platelet content ranged from 7% to 99%. Subgroup analysis showed little difference in mechanical behaviour between the F&P moderate-low and F&P moderate-high subgroups, with the F&P low and F&P high groups respectively exhibiting a decreased and increased stiffness. Comparing to current literature, the results demonstrated that analogues most accurately resemble thrombi with a low fibrin & platelet content. Furthermore, all samples displayed viscoelastic and non-linear stress-strain behaviour.Conclusion: It was found that composition is a strong influencing factor of thrombus mechanical properties. Both at high and low fibrin & platelet contents, the relation between composition and stiffness was strongest, while it was least pronounced at moderate fibrin & platelet contents (approximately 25%-75%).