Red blood cells (RBCs) clump together under low flow conditions in a process called RBC aggregation, which can alter RBC perfusion in a microvascular network. As elevated RBC aggregation is commonly associated with cardiovascular and inflammatory diseases, a better understanding of aggregation is essential. Unlike RBC aggregation in polymer solutions which can be well explained by polymer depletion theory, plasma-mediated RBC aggregation has features that best match explanations with cross-bridging mechanisms. Previous studies have demonstrated the dominant role of fibrinogen (Fg) in promoting aggregate formation and recent cell-force spectroscopy (CFS) experiments on interacting RBC doublets in plasma have reported an inverse relationship between disaggregation force and the adhesive contact area between RBCs. This has led investigators to revisit the hypothesis of inter-RBC cross-bridging which involves cross-bridge migration under interfacial tension during the forced disaggregation of RBC aggregates. In this study, we developed the cross-bridge migration model (CBMM) in plasma that mechanistically represents the migrating cross-bridge hypothesis. Transport of mobile Fg cross-bridges (mFg) was calculated using a convection-diffusion transport equation with our novel introduction of convective cross-bridge drift that arises due to intercellular friction. By parametrically transforming the diffusivity of mFg in the CBMM, we were able to match experimental observations of both RBC doublet formation kinematics and RBC doublet disaggregation forces under optical tweezers tension. We found that non-specific cross-bridging promotes spontaneous growth of adhesion area between RBC doublets whereas specific cross-bridging tends to prevent adhesion area growth. Our CBMM was also able to correlate Fg concentration shifts from healthy population blood plasma to SLE (lupus) condition blood plasma with the observed increase in doublet disaggregation forces for the RBC doublets in SLE plasma.

Ultrasound speckle image of blood is mainly attributed by red blood cells (RBCs) which tend to form RBC aggregates. RBC aggregates are separated into individual cells when the shear force is over a certain value. The dissociation of RBC aggregates has an influence on the performance of ultrasound speckle image velocimetry (SIV) technique in which a cross-correlation algorithm is applied to the speckle images to get the velocity field information. The present study aims to investigate the effect of the dissociation of RBC aggregates on the estimation quality of SIV technique. Ultrasound B-mode images were captured from the porcine blood circulating in a mock-up flow loop with varying flow rate. To verify the measurement performance of SIV technique, the centerline velocity measured by the SIV technique was compared with that measured by Doppler spectrograms. The dissociation of RBC aggregates was estimated by using decorrelation of speckle patterns in which the subsequent window was shifted as much as the speckle displacement to compensate decorrelation caused by in-plane loss of speckle patterns. The decorrelation of speckles is considerably increased according to shear rate. Its variations are different along the radial direction. Because the dissociation of RBC aggregates changes ultrasound speckles, the estimation quality of SIV technique is significantly correlated with the decorrelation of speckles. This degradation of measurement quality may be improved by increasing the data acquisition rate. This study would be useful for simultaneous measurement of hemodynamic and hemorheological information of blood flows using only speckle images.