Thromboembolic conditions are a leading global cause of mortality and a major cause of disability. Throughout the years mechanical thrombectomy has become a preferred method of treatment over thrombolysis. Mechanical thrombectomy devices utilize either aspiration or various methods of grasping to remove blood clots. Although a variety of MT devices are now in clinical use they all face some trade-offs depending on the removal method they use. This study proposes a novel thrombectomy device. The design implements a strategy of simultaneously gripping the clot and expanding the vessel lumen in order to reduce friction while advancing along the clot’s length in incremental steps. The prototype has been evaluated in a custom-made experimental setup using phantom vessels and thrombi analogs. The proof-of-concept experiments have shown that the device can successfully remove thrombi. The study shows promising results for this new kind of device and can be a foundation for future research into applying similar removal strategies in thrombectomy.

Stroke, caused by large vessel occlusions, is the second leading cause of death worldwide. Large vessel occlusions are the result of thrombosis, the undesired coagulation of blood within the vasculature. Due to this coagulation, a vessel can get blocked, prohibiting blood flow to areas distal from the occlusion, with all the serious consequences that may ensue. Since 2015, mechanical thrombectomy procedures have been widely accepted as a successful treatment technique to remove thrombi from the vasculature. However, complete reperfusion is only reached in 50% of acute ischemic stroke cases.

To successfully remove a thrombus from the vasculature, it is necessary to apply a specific retrieval force. This force must exceed the opposing forces, including the impaction force generated by the blood pressure gradient across the thrombus and the interaction forces between the thrombus and the vessel wall. Multiple studies have focused on tensile and compressive properties of thrombi. However, little is known about shear loading of the thrombus and about the interaction properties of the thrombus-vessel wall interface. Therefore, the aim of this study is to gain a better comprehension of thrombus biomechanics by studying the shear behavior of thrombi and the interaction of the thrombus-vessel wall interface in vitro.

In order to perform these in vitro studies, two custom-made test setups have been designed and developed. The friction test setup contains a plate of which the angle can be inclined slowly. By placing a thrombus-vessel wall sample on top of this plate, it is aimed to determine the static and kinetic coefficient of friction of the thrombus-vessel wall interface. Furthermore, it is aimed to determine the effect of time on this interaction. The thrombus-vessel wall interface was created by obtaining a piece of vein and blood from pigs. To study the shear behavior of thrombi a shear test setup has been developed. Two thrombi types have been utilized for this study, red blood cell- and fibrin-rich. Within the shear test setup it is possible to perform shear experiments under different normal loading conditions. A comprehensive analysis of the data acquired from experiments performed with both test setups has been conducted. Furthermore, a computational model has been developed to fit towards the experimental data obtained from the shear experiments.

The friction experiments suggest that time positively influences the bonds formed between a thrombus and the vessel wall as the coefficients of friction increase with an increased waiting time. Furthermore, a strong positive correlation was found between the static and kinetic coefficient of friction. This result was also found when doing an extensive analysis of the data obtained from the shear experiments. Additionally, the shear experiment showed that the thrombus composition influences its mechanical properties. Higher shear moduli and kinetic coefficients of friction were found for the fibrin samples, compared to the red blood cell samples.

The results obtained from the friction and shear experiments provide valuable insights into thrombus biomechanics. By extending the performed studies a better comprehension on thrombus mechanics and the thrombus-vessel wall interaction can be achieved.

Stroke, currently ranked as the second leading cause of mortality and the most prevalent source of enduring disability, imposes significant societal and economic consequences. These consequences encompass the necessity for extended care, rehabilitation, and the economic burdens associated with lost productivity. In the diagnostic process, physicians typically employ imaging techniques to assess cerebral blood vessels, ruling out alternative conditions when stroke is suspected. Subsequent to di agnosis, treatments like Intravenous Thrombolysis (IVT) and Endovascular Thrombectomy (EVT) are administered to either dissolve or retrieve thrombi. However, with EVT emerging as the new standard of stroke care and an increasing body of evidence indicating the substantial impact of thrombus me chanical properties on thrombectomy success, the use of clot analogues is gaining prominence as a means of facilitating efficient mechanical testing, both in terms of time and finances. By establishing a link between mechanical properties and image characteristic parameters, medical practitioners gain a better understanding of intracranial thrombi before embarking on surgical procedures. This knowledge can serve as a theoretical foundation for optimizing surgical instruments and devising effective surgical protocols in the future. In pursuit of these objectives, this study involved 29 patients and entailed several key steps: firstly, the extraction of imaging parameters from pre-EVT CT images; secondly, the creation of thrombus analogues from the patient’s blood; thirdly, the execution of five distinct mechanical tests to derive me chanical properties, encompassing cyclic compression, compression relaxation, tensile test to failure, tensile relaxation, and fracture testing. Additionally, the hyperelastic Yeoh model was utilized to simu late the behavior observed from cyclic compression and tensile to failure test. Prony series (n=2) was fitted to stress relaxation curves. In summary, this investigation revealed noteworthy observations pertaining to mechanical proper ties. Notably, hysteresis areas demonstrated robust and statistically significant correlations with com pression high-strain stiffness, low-strain stiffness, and tensile stiffness along with the ultimate tensile stress, implying that the thrombus analogue exhibits both hyperelastic and viscoelastic characteristics. In the domain of imaging parameters, the evident interdependence among the densities of the three regions of interest within both CTA and NCCT is apparent, respectively. However, it is essential to un derscore that the relationship between CTA and NCCT was not deemed statistically significant. Lastly, a noteworthy revelation was the strong negative monotonic correlation (ρ=-0.82, P=0.011) observed between the analogue contraction ratio of the thrombus analogue and the density of the middle part of NCCT in actual thrombi. This insight suggests that, in addition to thrombus composition, microstructure plays a pivotal role as well in determining their properties.

Abstract - Perfusion impairment of vessels by thrombus formation is the top global cause of death. Depending on the
location and disease pathology, thrombus composition varies, affecting treatment response and making identification of thrombus composition and its mechanical response sought after. The features of a fibrin network, which functions as the adhesive, have shown to influence thrombus strength, viscoelasticity, permeability and resilience to fibrinolysis. In previous studies, these features were analysed on fibrin gels made under static conditions, while in vivo thrombi are formed under flow. Therefore, the aim of this thesis is to form plasma thrombi in both the presence and absence of flow and evaluate the differences in the microstructure and mechanical properties.

Methods - Plasma thrombi in the presence and absence of flow were formed inside the Chandler loop. Recitrated PFP, pooled from three healthy volunteers, was to the Chandler loop tubings and spun at 0, 10 and 30 RPM to create shear rates of roughly 0 (static thrombus), 100 and 300 s^(-1) (flow thrombi). Six thrombi were formed for each shear rate, of which two were prepared for SEM imaging to determine the diameter of fibrin fibers. The other four thrombi were cut into three disks and were used for CLSM, unconfined compression testing and micro-indentation. With CLSM, the fiber density and pore size of the network were quantified and with unconfined compression testing and micro-indentation the global and local stiffness' of the thrombi, respectively. The global stiffness of the thrombi was measured at low (20-40\%) and high strains (75-80\%).

Results - Increased diameters were found for flow thrombi compared to static thrombi (p < 0.001 and p < 0.001). Furthermore, density increased p=0.017 and p=0.007) and pore size decreased (p < 0.001 and p < 0.001) for flow thrombi compared to static thrombi. Compression testing showed an increased stiffness for thrombi formed at 30 RPM compared to 0 and 10 RPM (20-40\%, p = 0.008 and p < 0.001 ; 75-80\%, p = 0.015 and p < 0.001). Lastly, only at high strains a significant stiffness increase was found between the 0 and 10 RPM (p=0.025).

Conclusions - The fiber diameter increased in the presence of flow compared to thrombi formed in the absence of flow. Furthermore, the density increased and the pore size decreased for flow thrombi compared to static thrombi. Lastly, the stiffness of the plasma thrombi was increased for the thrombi formed at 30 RPM compared to 0 and 10 RPM.

Acute Ischemic Stroke (AIS) is an abrupt onset of a focal neurological deficit due to the occlusion of a cerebral artery caused by thrombosis or embolism. According to the World Health Organization, stroke is the second leading cause of death in the world. One of the available treatments is the aspiration thrombectomy, where a negative pressure is applied to the thrombus in order to remove it from the vessel. In this work, the aspiration thrombectomy will be studied through the development of a computational model. By means of the development of this model, a baseline is created for exploratory research into both the technical and clinical aspects. The range of applied thrombus models in literature varies largely. In this work, the thrombus is modelled using a fluid material model. Through the application of this fluid model, an emphasis is put on the fluid properties of thrombi, which exhibit both solid and fluid behavior. Three fluid models are applied, of which two represent non-Newtonian fluid behavior and one Newtonian fluid behavior. The effects of these material models are assessed through the pressure and velocity distribution and the thrombus behavior. Furthermore, an evaluation of three clinical parameters, aspiration pressure, suction distance and thrombus length, is performed. Each parameter was assigned three variations, which are assessed based on the respective recanalization times. Each clinical parameter is evaluated to influence the recanalization time, albeit to different extents. In conclusion, this thesis functions as exploratory research in the development of computational aspiration thrombectomy models. Future research is advised, in the form of material model verification with patient-retrieved or analog clots or more extensive research into the relation between recanalization time and the presented clinical parameters.

Atherosclerotic plaque rupture is the underlying cause of 50% of deaths in western society. Although screening methodologies exist, plaques are highly complex, and the parameters used to measure plaque vulnerability are often insufficient for correct medical screening. Since plaque rupture occurs when the vascular forces exceed the plaque strength, the mechanical analysis of plaque stability could offer a new window into predicting rupture. By interpreting the mechanical behaviour of plaques, so-called mechanical markers could be derived, which could highlight vulnerable plaques before thrombosis. Unfortunately, the extensively modelled local stresses and energy functions are immeasurable in vivo. Therefore we turned to strains, a measure of material deformation that can be obtained clinically. This study investigates the predictive value of strain distributions in the early detection of fibrous caps rupture.
Simplistic plaque cap mimics were engineered to model atherosclerotic plaque rupture. Made from a fibrinous matrix and a soft lipidic inclusion (SI), the constructs were tailored to have mechanical properties similar to in vivo plaque caps. Tissue engineered caps offer a wide range of advantages over endarterectomy samples, including unlimited sample availability, robust geometry, high reproducibility and precise control over biological constituents. These constructs were uniaxially strained and subjected to 2D digital image correlation (DIC) to obtain their strain fields. Two-dimensional DIC is an algorithm that derives the material deformation by tracking surface features of its target sample. Therefore, it can very accurately calculate local strains for a material. This report analyses the patterns and maxima of the strain maps of five samples to evaluate unique features distinct at the rupture location that could serve as potential markers of plaque vulnerability. Besides inspecting the individual strain maps, their collective contribution through two strain-based failure criteria was analysed. These failure criteria approximate the strain energy in the samples.
The mechanical failure of the constructs was not instantaneous. All samples underwent failure in phases, starting with a small crack in the SI and concluding with the rupture of the fibrous tissue. Likewise, the strain and failure criteria patterns were consistent within all samples. Even though their strain values differ, the accumulations of low and high strains lie at nearly identical positions. These patterns emerged early in the tensile experiment, as the frames at a physiological (10%) and final (ultimate state before rupture) global strain measured a strong resemblance. In a more localised analysis, the fields were radially divided into ‘slices’ of data to produce distinct segment-based patterns. The rupture location consistently lies at a unique feature in the pattern, such as a peak or a valley. As was observed before, aside from the difference in their magnitude, the strain patterns showed no change between the frames. Finally, the local maxima of the strain and failure criteria maps were inspected. Their distances to the rupture site were comparable for all maps, indicating they performed similarly at estimating the rupture location. Moreover, the distances measured for the final frame showed no significant difference to those measured for the physiological frame.
The mechanical response of the five samples is similar. Aside from undergoing mechanical rupture in stages, the analysis of the tissue construct shows that a relationship exists between the local strains and rupture location. First, the rupture location always sits at the edge of a high valued region in the SI. Second, the tissue segmentation produces a highly reproducible pattern with a distinct colocalisation between segment patterns and the rupture location. Third, the maxima of the strain and failure criteria maps lie close to the rupture site, although they do not overlap. Accordingly, there is a clear relationship between the rupture location and the
local strain patterns.

Background- A wide variation in composition is found within the thrombi retrieved from acute ischemic stroke patients. The composition of a thrombus and its mechanical properties have a significant influence on the procedural ease and success rate of mechanical retrieval procedures. If the composition and mechanical properties of a thrombus could be determined using admission computed tomography (CT) imaging, the treatment could be adjusted to ensure a good outcome in each case. This study aims to investigate and associate three thrombus characteristics related to this issue: composition, mechanics, and CT imaging characteristics.
Methods- Blood was drawn from three healthy volunteers. Analog thrombi of different compositions were prepared by combining red blood cells (RBCs) and platelet-rich plasma (PRP) in five different volumetric ratios: 0% RBCs and 100% PRP, 20% RBCs and 80% PRP, 40% RBCs and 60% PRP, 60% RBCs and 40% PRP, 80% RBCs and 20% PRP. To measure thrombus contraction, the weight of the resulting thrombus was expressed as a percentage of the weight of the original blood mixture. First, CT imaging was performed using micro CT and clinical CT imaging to obtain density and perviousness measurements of the thrombi. Secondly, the thrombi were subjected to a cyclic unconfined compression test to analyse stress-strain behaviour and to determine low and high strain secant moduli as a measure for thrombus stiffness. Lastly, thrombus composition was analysed using histological techniques to quantify RBCs, fibrin and platelet conglomerations, fibrin, and white blood cells.
Results- First, a positive linear relationship was found between the relative thrombus weight after
contraction and the volumetric RBC ratio (r=0.98, p<0.001). Secondly, with composition analysis, it was found that the thrombi with the 0% 20%, 40%, 60%, and 80% volumetric RBC ratios produced thrombi with non-equivalent compositions of 0.0%, 89.8%, 95.1%, 97.4%, and 99.4% RBCs. This showed that only 0% RBC and RBC-rich (>85% RBC) thrombi were created. Thirdly, on clinical CT imaging, the 0% RBC samples were found to be significantly lower in mean density compared to the RBC-rich thrombi (36 HU and 88 HU respectively, p<0.001). Fourthly, the perviousness was significantly higher for the 0% RBC thrombi compared to the RBC-rich thrombi (An increase of >81 HU and <14 HU respectively, p<0.005). Fifthly, for the mechanics, the secant modulus at high strain decreased with an increasing amount of RBCs in the original volumetric ratio. For donor one the high strain stiffness values were 263, 84, 72, 27, and 13 kPa for an increasing RBC content. Lastly, thrombus stiffness differed per donor. For example, the high strain stiffnesses for 40% RBC thrombi were 72, 432,
and 33 kPa between donors. Thrombus density and perviousness on clinical CT imaging were significantly different for the 0% RBC and RBC-rich group (both p<0.001). High strain stiffness was significantly correlated to the contracted thrombus weight (r=-0.68 p=0.006).
Conclusions- Both density and perviousness on clinical CT imaging were related to the RBC content of the analog thrombi. For the thrombus mechanics, the high strain stiffness of the thrombi was highly correlated to the relative thrombus weight after contraction and moderately correlated to the RBC content. This implicates that clinical imaging should strive to measure thrombus contraction as well as composition to estimate thrombus mechanics prior to mechanical retrieval.