In Vitro Quantification of Time Dependent Thrombus Size Using Magnetic Resonance Imaging and Computational Simulations of Thrombus Surface Shear Stresses

Taylor, Joshua O.; Witmer, Kory P.; Neuberger, Thomas; Craven, Brent A.; Meyer, Richard S.; Deutsch, Steven; Manning, Keefe B.

doi:10.1115/1.4027613

Cited by 39 publications

(48 citation statements)

References 57 publications

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“…However, this is commonly done in similar thrombo-genesis modeling studies. [20,24,43,90] Moreover, inaccuracies incurred due to this assumption are believed to be small, since blood behaves close to a Newtonian fluid when the shear stress is larger than 1 Pa (which is our case). [45] The future directions for this work include performing similar measurements of the blood flow forces experienced by occlusive and embolizing thrombi (both of which are harder to induce and capture experimentally).…”

Section: Discussionmentioning

confidence: 89%

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In vivo measurement of blood clot mechanics from computational fluid dynamics based on intravital microscopy images

Kadri

Chandran

Surblyte

et al. 2019

Computers in Biology and Medicine

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Ischemia leading to heart attacks and strokes is the major cause of deaths in the world. Whether an occlusion occurs or not, depends on the ability of a growing thrombus to resist forces exerted on its structure. This manuscript provides the first known in vivo measurement of the stresses that clots can withstand, before yielding to the surrounding blood flow. Namely, Lattice-Boltzmann Method flow simulations are performed based on 3D clot geometries. The latter are estimated from intravital microscopy images of laser-induced injuries in cremaster microvasculature of live mice. In addition to reporting the blood clot yield stresses, we also show that the thrombus "core" does not experience significant deformation, while its "shell" does. This indicates that the latter is more prone to embolization. Hence, drugs should be designed to target the shell selectively, while leaving the core intact (to minimize excessive bleeding). Finally, we laid down a foundation for a nondimensionalization procedure, which unraveled a relationship between clot mechanics and biology. Hence, the proposed framework could ultimately lead to a unified theory of thrombogenesis, capable of explaining all clotting events. Thus, the findings presented herein will be beneficial to the understanding and treatment of heart attacks, strokes and hemophilia.

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Section: Discussionmentioning

confidence: 89%

“…For example, in refs. [24,30,43,44] such models were used to calculate the time-dependent effects of surface shear stresses on thrombi developed in vitro. However, as mentioned previously, in vitro experiments may not depict realistic physiological conditions observed in vivo.…”

Section: Proposed Hybrid Image-based Modeling Approach and 3d Clot Smentioning

confidence: 99%

In vivo measurement of blood clot mechanics from computational fluid dynamics based on intravital microscopy images

Kadri

Chandran

Surblyte

et al. 2019

Computers in Biology and Medicine

View full text Add to dashboard Cite

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“…The relationship between our simulated timescale and real timescale was examined, using a backward-facing step under steady flow. The simulation results obtained with an augmentation factor of 150 for coagulant diffusivity were compared with experimental data [28], and there was a good agreement between predictions obtained after a simulation time of 40 s and measurements taken at 90 min, suggesting that the simulation time could be multiplied by the augmentation factor (40 × 150 = 6000 s) to roughly estimate the equivalent real time (90 min = 5400 s). However, such a simple relation may not apply to pulsatile flow, as the interface between diffusion-dominated and convection-dominated domains hinders the transport of proteins and coagulation factors to the clot surface.…”

Section: Discussionmentioning

confidence: 99%

Predicting false lumen thrombosis in patient-specific models of aortic dissection

Menichini

Cheng

Gibbs

et al. 2016

J. R. Soc. Interface.

116

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Aortic dissection causes splitting of the aortic wall layers, allowing blood to enter a ‘false lumen’ (FL). For type B dissection, a significant predictor of patient outcomes is patency or thrombosis of the FL. Yet, no methods are currently available to assess the chances of FL thrombosis. In this study, we present a new computational model that is capable of predicting thrombus formation, growth and its effects on blood flow under physiological conditions. Predictions of thrombus formation and growth are based on fluid shear rate, residence time and platelet distribution, which are evaluated through convection–diffusion–reaction transport equations. The model is applied to a patient-specific type B dissection for which multiple follow-up scans are available. The predicted thrombus formation and growth patterns are in good qualitative agreement with clinical data, demonstrating the potential applicability of the model in predicting FL thrombosis for individual patients. Our results show that the extent and location of thrombosis are strongly influenced by aortic dissection geometry that may change over time. The high computational efficiency of our model makes it feasible for clinical applications. By predicting which aortic dissection patient is more likely to develop FL thrombosis, the model has great potential to be used as part of a clinical decision-making tool to assess the need for early endovascular intervention for individual dissection patients.

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“…Ha et el. [36] and Taylor et al [38] found that platelet deposition onto collagen initially occurred on the edge of a sudden expansion but then progressed into the corner. The crevices are similar to a sudden expansion followed quickly by a sudden constriction.…”

Section: Discussionmentioning

confidence: 99%

Visualization and analysis of biomaterial-centered thrombus formation within a defined crevice under flow

Jamiolkowski

Pedersen

et al. 2016

Biomaterials

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The blood flow pathway within a device, together with the biomaterial surfaces and status of the patient’s blood, are well-recognized factors in the development of thrombotic deposition and subsequent embolization. Blood flow patterns are of particular concern for devices such as blood pumps (i.e. ventricular assist devices, VADs) where shearing forces can be high, volumes are relatively large, and the flow fields can be complex. However, few studies have examined the effect of geometric irregularities on thrombus formation on clinically relevant opaque materials under flow. The objective of this study was to quantify human platelet deposition onto Ti6Al4V alloys, as well as positive and negative control surfaces, in the region of defined crevices (~50–150 µm in width) that might be encountered in many VADs or other cardiovascular devices. To achieve this, reconstituted fresh human blood with hemoglobin-depleted red blood cells (to achieve optical clarity while maintaining relevant rheology), long working optics, and a custom designed parallel plate flow chamber were employed. The results showed that the least amount of platelet deposition occurred in the largest crevice size examined, which was counterintuitive. The greatest levels of deposition occurred in the 90 µm and 53 µm crevices at the lower wall shear rate. The results suggest that while crevices may be unavoidable in device manufacturing, the crevice size might be tailored, depending on the flow conditions, to reduce the risk of thromboembolic events. Further, these data might be used to improve the accuracy of predictive models of thrombotic deposition in cardiovascular devices to help optimize the blood flow path and reduce device thrombogenicity.

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In Vitro Quantification of Time Dependent Thrombus Size Using Magnetic Resonance Imaging and Computational Simulations of Thrombus Surface Shear Stresses

Cited by 39 publications

References 57 publications

In vivo measurement of blood clot mechanics from computational fluid dynamics based on intravital microscopy images

In vivo measurement of blood clot mechanics from computational fluid dynamics based on intravital microscopy images

Predicting false lumen thrombosis in patient-specific models of aortic dissection

Visualization and analysis of biomaterial-centered thrombus formation within a defined crevice under flow

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