(408b) In Vivo Measurement of Blood Clot Strength from Computational Fluid Dynamics Based on Intravital Microscopy Images

mso-add-space:auto;text-align:justify;line-height:normal">Prevention of
excessive bleeding via formation of clots/thrombus following vascular injuries
is essential for the survival of living organisms that possess closed
high-pressure circulatory systems. However, pathological manifestations of
thrombosis and embolism can potentially lead to life-threatening complications
when occurring in the heart (i.e., a heart attack), brain (i.e., a stroke), or
lungs (i.e., deep vein thrombosis/pulmonary embolism). Among these,
thrombo-embolic infarction is the leading cause of mortality and morbidity in
the United States, while stroke is the fifth.

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mso-add-space:auto;text-align:justify;line-height:normal">The fate of any
blood clot (i.e. whether or not it grows, becomes occlusive or embolizes) depends on its ability to resist the fluid-induced
forces exerted on its structure by the surrounding blood flow. This resistance
force provides a measure of the clots' deformation or “yielding’ strength.
Unfortunately, because the deformation of clots in blood vessels occur very
fast, it is difficult to obtain in vivo
estimates of the forces required using experimental techniques.

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normal"> " times new roman italic>Figure 1  “Heatmap” of the LBM
fluid-induced surface shear stress, calculated using the constant pressure drop
boundary condition. The results are shown at different time points (a
dimensionless t* scale is used " times new roman italic>to collapse thrombogenesis data from multiple clots onto a single
master curve) font-family:" times new roman mso-bidi-font-style:italic>. t* = 0.023 is an earlier time in the thrombus
formation process; t 9.0pt;font-family:" cambria math color:windowtext>∗ = 0.5
is the time marking the beginning of deformation/yielding; t∗ mso-bidi-font-size:9.0pt;font-family:" times new roman font-style:normal> = 1 is the time
marking the end of deformation/yielding, when significant mass is transferred
to the back of the clot; t 9.0pt;font-family:" cambria math color:windowtext>∗ = 2.67
is a later time after thrombus yielding during which thrombus has assumed its
final shape. The black arrow indicates direction of blood flow. 12.0pt;font-family:" times new roman mso-bidi-font-style:italic>

mso-add-space:auto;text-align:justify;line-height:normal">This work provides
the first known in vivo measurement
of how much stress a clot can withstand, before yielding to the surrounding
blood flow.  We use an approach that
combines computational modeling and experimental imaging data. Namely,
Lattice-Boltzmann Method flow simulations are performed based on 3D clot
geometries, which are estimated from intravital microscopy images of
laser-induced injuries in cremaster microvasculature of live mice. This hybrid
approach helps overcome the limitation of utilizing pure computational modeling
or experimental measurements alone.  Figure 1 above shows a sample
calculation of the stresses exerted on a blood clot at different time
points. 

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mso-add-space:auto;text-align:justify;line-height:normal">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 shell is more prone to embolization. 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. To take advantage of these results,
drugs can be designed to target the shell selectively, while leaving the core
intact to minimize excessive bleeding. Also, yield stress estimates obtained
can provide critical information for design of thromboectomy devices used to
mechanically remove harmful blood clots from patients. Overall, the findings
presented herein will be beneficial to the understanding and treatment of heart
attacks, strokes and hemophilia.