Browsing by Author "Xu, Zhiliang"

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    Model predictions of deformation, embolization and permeability of partially obstructive blood clots under variable shear flow
    (The Royal Society, 2017-11) Xu, Shixin; Xu, Zhiliang; Kim, Oleg V.; Litvinov, Rustem I.; Weisel, John W.; Alber, Mark; Medicine, School of Medicine
    Thromboembolism, one of the leading causes of morbidity and mortality worldwide, is characterized by formation of obstructive intravascular clots (thrombi) and their mechanical breakage (embolization). A novel two-dimensional multi-phase computational model is introduced that describes active interactions between the main components of the clot, including platelets and fibrin, to study the impact of various physiologically relevant blood shear flow conditions on deformation and embolization of a partially obstructive clot with variable permeability. Simulations provide new insights into mechanisms underlying clot stability and embolization that cannot be studied experimentally at this time. In particular, model simulations, calibrated using experimental intravital imaging of an established arteriolar clot, show that flow-induced changes in size, shape and internal structure of the clot are largely determined by two shear-dependent mechanisms: reversible attachment of platelets to the exterior of the clot and removal of large clot pieces. Model simulations predict that blood clots with higher permeability are more prone to embolization with enhanced disintegration under increasing shear rate. In contrast, less permeable clots are more resistant to rupture due to shear rate-dependent clot stiffening originating from enhanced platelet adhesion and aggregation. These results can be used in future to predict risk of thromboembolism based on the data about composition, permeability and deformability of a clot under specific local haemodynamic conditions.
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    Segmentation, Reconstruction, and Analysis of Blood Thrombus Formation in 3D 2-Photon Microscopy Images
    (SpringerOpen, 2009-09-06) Mu, Jian; Liu, Xiaomin; Kamocka, Malgorzata M.; Xu, Zhiliang; Alber, Mark S.; Rosen, Elliot D.; Chen, Danny Z.; Medical and Molecular Genetics, School of Medicine
    We study the problem of segmenting, reconstructing, and analyzing the structure growth of thrombi (clots) in blood vessels in vivo based on 2-photon microscopic image data. First, we develop an algorithm for segmenting clots in 3D microscopic images based on density-based clustering and methods for dealing with imaging artifacts. Next, we apply the union-of-balls (or alpha-shape) algorithm to reconstruct the boundary of clots in 3D. Finally, we perform experimental studies and analysis on the reconstructed clots and obtain quantitative data of thrombus growth and structures. We conduct experiments on laser-induced injuries in vessels of two types of mice (the wild type and the type with low levels of coagulation factor VII) and analyze and compare the developing clot structures based on their reconstructed clots from image data. The results we obtain are of biomedical significance. Our quantitative analysis of the clot composition leads to better understanding of the thrombus development, and is valuable to the modeling and verification of computational simulation of thrombogenesis.
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    Strong Binding of Platelet Integrin αIIbβ3 to Fibrin Clots: Potential Target to Destabilize Thrombi
    (Nature Publishing group, 2017-10-11) Höök, Peter; Litvinov, Rustem I.; Kim, Oleg V.; Xu, Shixin; Xu, Zhiliang; Bennett, Joel S.; Alber, Mark S.; Weisel, John W.; Medicine, School of Medicine
    The formation of platelet thrombi is determined by the integrin αIIbβ3-mediated interactions of platelets with fibrinogen and fibrin. Blood clotting in vivo is catalyzed by thrombin, which simultaneously induces fibrinogen binding to αIIbβ3 and converts fibrinogen to fibrin. Thus, after a short time, thrombus formation is governed by αIIbβ3 binding to fibrin fibers. Surprisingly, there is little understanding of αIIbβ3 interaction with fibrin polymers. Here we used an optical trap-based system to measure the binding of single αIIbβ3 molecules to polymeric fibrin and compare it to αIIbβ3 binding to monomeric fibrin and fibrinogen. Like αIIbβ3 binding to fibrinogen and monomeric fibrin, we found that αIIbβ3 binding to polymeric fibrin can be segregated into two binding regimes, one with weaker rupture forces of 30–60 pN and a second with stronger rupture forces >60 pN that peaked at 70–80 pN. However, we found that the mechanical stability of the bimolecular αIIbβ3-ligand complexes had the following order: fibrin polymer > fibrin monomer > fibrinogen. These quantitative differences reflect the distinct specificity and underlying molecular mechanisms of αIIbβ3-mediated reactions, implying that targeting platelet interactions with fibrin could increase the therapeutic indices of antithrombotic agents by focusing on the destabilization of thrombi rather than the prevention of platelet aggregation.