Fig 1.
The schematic of the experiment set-up.
The width and the height of the chamber is 1 mm and 100 μm, respectively. The dimension of the recorded experimental domain is 125 μm × 100 μm × 100 μm.
Fig 2.
Flow diagram for the image-based modelling methodology implemented in this work.
Experiment: microscopy images of platelet aggregates with labelled and non-labelled platelets caught by differential interference contrast microscopy with 100x magnification. Extracted information: reconstructed platelet aggregate geometry and permeability distribution over the aggregate. Computational modelling: the simulated domain for blood flow.
Fig 3.
Fluorescence intensity (arbitrary units)—Density relation inside platelet aggregates.
(a) 800 s−1 WSR. Slope = 0.0027. Intercept = -0.19. (b) 1600 s−1 WSR. Slope = 0.0014. Intercept = 0.28. (c) 4000 s−1 WSR. Slope = 0.0004. Intercept = -0.23. The unit in each subfigure is different due to the influence of external environment such as exposure level and labelling time.
Fig 4.
Schematic diagram of the simulation domain.
(a) Blood perfusion channel and the location of the simulated domain. (b) Top view of the blood perfusion channel. (c) Domain of the blood flow simulation including the position of the platelet aggregate.
Table 1.
Parameter used in simulations.
Fig 5.
Distribution of fluorescence intensity, distribution of platelet aggregates density and permeability under 800 s−1, 1600 s−1 and 4000 s−1 WSRs.
(a)-(c) Distributions of fluorescence intensity inside the platelet aggregates. (d) Average volume fraction of platelets of the platelet aggregates. (e) Distribution of volume fraction of platelets inside the platelet aggregates. (f) Distribution of permeability inside the platelet aggregates in log-scale.
Fig 6.
Intensity of the fluorescence, corresponding porosity and the permeability of the platelet aggregate under 1600 s−1 WSR.
(a) Intensity of the fluorescence obtained from the experimental data. (b) Corresponding porosity of the platelet aggregate. (c) Permeability of the platelet aggregate on the cross-sections of the aggregate obtained from the Kozeny-Carman equation. The results inside the platelet aggregates formed under 800 s−1 and 4000 s−1 WSRs are demonstrated in S1 Fig.
Fig 7.
Flow field at WSR of 1600 s−1.
(a) The velocity field of the blood flow on a cross-section of the flow domain. The red arrow indicates the direction of blood flow. (b) The velocity field of the blood flow inside the platelet aggregate on the cross-sections. The orange arrow points out the high flow velocity area between the shell and the core.
Fig 8.
Stress analysis of the blood flow and the platelet aggregate under 1600 s−1 WSR.
(a) The kinetic force exerted on the platelet aggregate. (b) The fluid shear stress on the surface of the platelet aggregate. The simulation results inside the platelet aggregates formed under 800 s−1 and 4000 s−1 WSRs are shown in S2 Fig.
Fig 9.
Advection-diffusion balance of (a) Ca2+, (b) ADP and (c) Factor X on cross-sections inside the platelet aggregate under 1600 s−1 WSR. The upper end of the color scale is set to 1. Therefore, areas with red color correspond to advection-dominated regions, while colors towards the lower end of the scale denote diffusion-dominated regions.
Table 2.
Intrathrombus transport simulation for coagulation factors with different molecular weights at WSR of 1600 s−1.
Table 3.
Comparison of simulation results under various WSRs.
Fig 10.
Platelet aggregates geometries, shear rates and the rate of elongation.
(a)-(c) Geometries of the platelet aggregates under 800 s−1, 1600 s−1 and 4000 s−1 WSRs flow condition. (d)-(f) Cross-sectional shear rate profile under 800 s−1, 1600 s−1 and 4000 s−1 WSRs flow condition. (g)-(i) Cross-sectional elongation rate profile under 800 s−1, 1600 s−1 and 4000 s−1 WSRs flow condition.
Fig 11.
Comparison of intrathrombus condition for different porosity values.
(a) Average blood flow velocity inside the platelet aggregates under various shear flow conditions. (b) Advection-dominated volume of ADP inside the platelet aggregates under various shear flow conditions. (c) Advection-dominated volume of Ca2+, ADP and Factor X inside the platelet aggregates under WSR of 1600 s−1.
Fig 12.
Comparison of intrathrombus condition for different porosity ranges.
(a) Average blood flow velocity inside the platelet aggregates under various shear flow conditions. (b) Advection-dominated volume of ADP inside the platelet aggregates under various shear flow conditions. (c) Advection-dominated volume of Ca2+, ADP and Factor X inside the platelet aggregates under WSR of 1600 s−1.
Fig 13.
Velocity magnitude of the blood flow inside the platelet aggregates under three WSRs.
(a) 800 s−1, (b) 1600 s−1 and (c) 4000 s−1. The arrows point out the high flow velocity area between the shell and the core.