A multiscale biomechanical model of platelets: Correlating with in-vitro results

Zhang, Peng; Zhang, Li; Slepian, Marvin J.; Deng, Yuefan; Bluestein, Danny

doi:10.1016/j.jbiomech.2016.11.019

Cited by 50 publications

(43 citation statements)

References 48 publications

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“…Laser illumination was masked at the midplane to reduce the amount of background noise caused by out-of-focus particles. Seven phases of the cardiac cycle were gathered at the mean cardiac outputs of 2 and 5 l min 21 . Each phase consisted of 250 image pairs.…”

Section: Validation Experimentsmentioning

confidence: 99%

“…Hence, significant effort has been directed towards understanding, minimizing and avoiding thrombosis in the cardiovascular system and on implantable devices. Studies have progressed from extensive in vivo [16,18] and in vitro [19,20] studies to modern multi-scale numerical simulations [21,22]. Additionally, substantial focus is on identifying and defining metrics that characterize flow-mediated thrombogenic potential in the cardiovascular system.…”

Section: Introductionmentioning

confidence: 99%

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Three-dimensional extent of flow stagnation in transcatheter heart valves

Raghav

Clifford

Midha

et al. 2019

J. R. Soc. Interface.

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The recent unexpected discovery of thrombosis in transcatheter heart valves (THVs) has led to increased concerns of long-term valve durability. Based on the clinical evidence combined with Virchow's triad, the primary hypothesis is that low-velocity blood flow around the valve could be a primary cause for thrombosis. However, due to limited optical access in such unsteady three-dimensional biomedical flows, measurements are challenging. In this study, for the first time, we employ a novel single camera volumetric velocimetry technique to investigate unsteady three-dimensional cardiovascular flows. Validation of the novel volumetric velocimetry technique with standard planar particle image velocimetry (PIV) technique demonstrated the feasibility of adopting this new technique to investigate biomedical flows. This technique was used to quantify the three-dimensional velocity field in the vicinity of a validated, custom developed, transparent THV in a bench-top pulsatile flow loop. Large volumetric regions of flow stagnation were observed in the neo-sinus throughout the cardiac cycle, with stagnation defined as a velocity magnitude lower than 0.05 m s −1 . The volumetric scalar viscous shear stress quantified via the three-dimensional shear stress tensor was within the range of low shear-inducing thrombosis observed in the literature. Such high-fidelity volumetric quantitative data and novel imaging techniques used to obtain it will enable fundamental investigation of heart valve thrombosis in addition to providing a reliable and robust database for validation of computational tools.

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Section: Validation Experimentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Three-dimensional extent of flow stagnation in transcatheter heart valves

Raghav

Clifford

Midha

et al. 2019

J. R. Soc. Interface.

View full text Add to dashboard Cite

show abstract

“…Existing simulation studies of platelet adhesion utilize techniques such as the boundary element method (12,(19)(20)(21), the immersed boundary method (22), and dissipative particle dynamics (23). In these simulations, platelets are modeled as rigid oblate spheroids.…”

Section: Introductionmentioning

confidence: 99%

“…This unique tumbling motion of platelets influences the contact area between a platelet and the channel wall, and thus a spherical platelet model is not sufficient for the study of platelet adhesion (19,25). In addition to the adhesion kinetics, the deformable red blood cells are included in these simulations to account for their influence on platelets (12,23). It is now feasible to simulate hemostasis from the initial single-platelet adhesion to the eventual clot formation in a whole-blood suspension.…”

Section: Introductionmentioning

confidence: 99%

In Vitro Measurement and Modeling of Platelet Adhesion on VWF-Coated Surfaces in Channel Flow

Dunne

Oglesby

et al. 2019

Biophysical Journal

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The process of platelet adhesion is initiated by glycoprotein (GP)Ib and GPIIbIIIa receptors on the platelet surface binding with von Willebrand factor on the vascular walls. This initial adhesion and detachment of a single platelet is a complex process that involves multiple bonds forming and breaking and is strongly influenced by the surrounding blood-flow environment. In addition to bond-level kinetics, external factors such as shear rate, hematocrit, and GPIb and GPIIbIIIa receptor densities have also been identified as influencing the platelet-level rate constants in separate studies, but this still leaves a gap in understanding between these two length scales. In this study, we investigate the fundamental relationship of the dynamics of platelet adhesion, including these interrelating factors, using a coherent strategy. We build a, to our knowledge, novel and computationally efficient multiscale model accounting for multibond kinetics and hydrodynamic effects due to the flow of a cellular suspension. The model predictions of platelet-level kinetics are verified by our microfluidic experiments, which systematically investigate the role of each external factor on platelet adhesion in an in vitro setting. We derive quantitative formulas describing how the rates of platelet adhesion, translocation, and detachment are defined by the molecular-level kinetic constants, the local platelet concentration near the reactive surface determined by red-blood-cell migration, the platelet effective reactive area due to its tumbling motion, and the platelet surface receptor density. Furthermore, if any of these aspects involved have abnormalities, e.g., in a disease condition, our findings also have clinical relevance in predicting the resulting change in the adhesion dynamics, which is essential to hemostasis and thrombosis.

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“…While continuum-level hemodynamics plays a crucial role in thrombus formation and its final size and shape within a false lumen, the cellular and sub-cellular-scale hemostatic processes (e.g., platelet adhesion, aggregation and coagulation kinetics) cannot be ignored and must be taken into account in any multiscale model (see e.g., [13][14][15] ). We propose here a data-driven mulitscale numerical approach to address thrombus formation in dissecting geometries, whose length scales are significantly larger than microscopic scales encountered at the cellular levels.…”

Section: Introductionmentioning

confidence: 99%

Data-driven Modeling of Thrombus Size and Shape in Aortic Dissections: Role of Hemodynamics

Yazdani

Bersi

et al. 2017

Preprint

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Aortic dissection is a pathology that manifests due to micro-structural defects in the aortic wall. Blood enters the damaged wall through an intimal tear, thereby creating a so-called false lumen and exposing the blood to thrombogenic intramural constituents such as collagen. The natural history of this acute vascular injury thus depends, in part, on thrombus formation, maturation, and possible healing within the false lumen. A key question is: Why do some false lumens thrombose completely while other thrombose partially or little at all? An ability to predict the location and extent of thrombus in subjects with dissection could contribute significantly to clinical decision-making, including interventional design. We develop, for the first time, a data-driven particle-continuum model for thrombus formation in a murine model of aortic dissection. In the proposed model, we simulate a final-value problem in lieu of the original initial-value problem with significantly fewer particles that may grow in size upon activation, representing the local concentration of blood-borne species. Numerical results confirm that geometry and local hemodynamics play significant roles in the acute progression of thrombus. Despite geometrical differences between murine and human dissections, mouse models can provide considerable insight and have gained in popularity owing to their reproducibility. Our results for three classes of geometrically different false lumens show that thrombus forms and extends to a greater extent in regions with lower bulk shear rates. Dense thrombi are less likely to form in high-shear zones and in the presence of strong vortices. The present data-driven study suggests that the proposed model is robust and can be employed to assess thrombus formation in human aortic dissections.

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A multiscale biomechanical model of platelets: Correlating with in-vitro results

Cited by 50 publications

References 48 publications

Three-dimensional extent of flow stagnation in transcatheter heart valves

Three-dimensional extent of flow stagnation in transcatheter heart valves

In Vitro Measurement and Modeling of Platelet Adhesion on VWF-Coated Surfaces in Channel Flow

Data-driven Modeling of Thrombus Size and Shape in Aortic Dissections: Role of Hemodynamics

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