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

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Abstract

The mouse laser injury thrombosis model provides up to 0.22 μm-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 cm2). Average wall shear stresses were 80–100 dyne/cm2 (peak values >200 dyne/cm2) on the outer rough surface of the thrombus. Within the thrombus, small molecule tracers (0.1 kDa) experienced ~70,000 collisions/s and penetrated/exited it in about 1 s, whereas proteins (~50 kDa) had ~9000 collisions/s and required about 10 s (tortuosity ~2–2.5). These simulations help define physical processes during thrombosis and constraints for drug delivery to the thrombus.

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Acknowledgments

We acknowledge financial support from NIH R01-HL103419 and AHA 11POST6890012 grants. Computation was carried under TERAGRID supercomputing allocation TG-IBN110004 on the Lonestar linux cluster (Texas Advanced Computing Center). We would also like to acknowledge Dr. Papavassiliou’s Computational Transport Processes Laboratory at the University of Oklahoma, since a considerable portion of the code used in this study was written as a part of a PhD dissertation there. Finally, we would like to thank Dr. Henry J. Neeman, Dr. Raghu Reddy, and the whole OU Supercomputing Center for Education & Research (OSCER) team for useful discussions and suggestions.

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Authors and Affiliations

  1. Department of Chemical and Biomolecular Engineering, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Roman S. Voronov & Scott L. Diamond

  2. Department of Medicine and Pharmacology, University of Pennsylvania, Philadelphia, PA, USA

    Timothy J. Stalker & Lawrence F. Brass

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  1. Roman S. Voronov
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  2. Timothy J. Stalker
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Correspondence to Scott L. Diamond.

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Associate Editor Konstantinos Konstantopoulos oversaw the review of this article.

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Voronov, R.S., Stalker, T.J., Brass, L.F. et al. Simulation of Intrathrombus Fluid and Solute Transport Using In Vivo Clot Structures with Single Platelet Resolution. Ann Biomed Eng 41, 1297–1307 (2013). https://doi.org/10.1007/s10439-013-0764-z

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