(470c) Intra-Thrombus Fluid and Molecular Transport Based On in-Vivo Imaging with Single Platelet Resolution

The assembly of platelet deposits and fibrin polymerization results in over 1 million heart attacks and strokes each year in the US. Conversely, deficiencies in these processes result in bleeding risks that confront surgeons on a regular basis. Motivated by recent ability of intravital microscopy experiments to image thrombus structure with a single platelet resolution, we set out to study intra-thrombus microenvironment via an approach that combines in-vivo laser injury experiments in mouse cremaster muscle arterioles, fluorescent confocal imaging with single platelet resolution, Optical Doppler velocimetry and supercomputer Lattice Boltzmann method fluid dynamics simulations. 

In this presentation we report fluid velocities, surface stresses and Darcy permeabilities that were calculated locally to the thrombus structure. Furthermore, in order to explore effects of molecular size on transport through the thrombus, movement of coagulation molecules corresponding to small (Ca), medium (ADP) and large (Factor X) molecular weights was studied using passive scalar tracking coupled with Brownian motion.  In one mode of release the molecules were released at the injury site below the thrombus.  Their motion was tracked under the in-vivo blood flow conditions and without flow, for comparison. In the second mode of release we studied how molecules from the bulk lumen diffused to the injury site. The methodology and findings reported herein enhance the understanding of fundamental transport processes that occur within the thrombus, and could have implications for therapeutic strategies that target drug delivery to local areas within the thrombus structure.