Simulation of Intrathrombus Fluid and Solute Transport Using In Vivo Clot Structures with Single Platelet Resolution

The mouse laser injury thrombosis model provides up to 0.22 mu m-resolved voxel information about the pore architecture of the dense inner core and loose outer shell regions of an in vivo arterial thrombus. Computational studies were conducted on this 3D structure to quantify transport within and around the clot: Lattice Boltzmann method defined vessel hemodynamics, while passive Lagrangian Scalar Tracking with Brownian motion contribution simulated diffusive-convective transport of various inert solutes (released from lumen or the injured wall). For an input average lumen blood velocity of 0.478 cm/s (measured by Doppler velocimetry), a 0.2 mm/s mean flow rate was obtained within the thrombus structure, most of which occurred in the 100-fold more permeable outer shell region (calculated permeability of the inner core was 10(-11) cm(2)). Average wall shear stresses were 80-100 dyne/cm(2) (peak values > 200 dyne/cm(2)) on the outer rough surface of the thrombus. Within the thrombus, small molecule tracers (0.1 kDa) experienced similar to 70,000 collisions/s and penetrated/exited it in about 1 s, whereas proteins (similar to 50 kDa) had similar to 9000 collisions/s and required about 10 s (tortuosity similar to 2-2.5). These simulations help define physical processes during thrombosis and constraints for drug delivery to the thrombus.