TY - JOUR
T1 - In vivo measurement of blood clot mechanics from computational fluid dynamics based on intravital microscopy images
AU - Kadri, Olufemi Emmanuel
AU - Chandran, Vishnu Deep
AU - Surblyte, Migle
AU - Voronov, Roman S.
N1 - Funding Information:
We would like to thank the Prof. Skip Brass laboratory (including Prof. Timothy J. Stalker and Dr. John D. Welsh) at the University of Pennsylvania's Perelman School of Medicine for performing all the experiments and sharing their microscopy data. Also, we acknowledge that a part of this work was initiated under the guidance of Prof. Scott L. Diamond at the University of Pennsylvania Department of Chemical and Biomolecular Engineering, and Bioengineering Institute for Medicine & Engineering.The study was financially supported by the New Jersey Health Foundation Grant #PC101-17, and in part by NIH R01-HL103419 “Blood Systems Biology” grant and AHA 11POST6890012 Postdoctoral Fellowship. Undergraduate labor was supported by Shodor's Blue Waters 2018–2019 Student Internship Program.We also acknowledge that computational resources were provided by the National Center for Supercomputing Applications at the University of Illinois at Urbana-Champaign, Texas Advanced Computing Center (TACC) at the University of Texas at Austin; Allocations: TG-BCS170001 and TG-BIO160074 by the Extreme Science and Engineering Discovery Environment (XSEDE) [91], which is supported by National Science Foundation grant number ACI-1548562.
Funding Information:
We also acknowledge that computational resources were provided by the National Center for Supercomputing Applications at the University of Illinois at Urbana-Champaign , Texas Advanced Computing Center (TACC) at the University of Texas at Austin ; Allocations: TG-BCS170001 and TG-BIO160074 by the Extreme Science and Engineering Discovery Environment (XSEDE) [ 91 ], which is supported by National Science Foundation grant number ACI-1548562 .
Funding Information:
The study was financially supported by the New Jersey Health Foundation Grant #PC101-17 , and in part by NIH R01-HL103419 “Blood Systems Biology” grant and AHA 11POST6890012 Postdoctoral Fellowship. Undergraduate labor was supported by Shodor's Blue Waters 2018–2019 Student Internship Program.
Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2019/3
Y1 - 2019/3
N2 - Ischemia which leads to heart attacks and strokes is one of the major causes of death in the world. Whether an occlusion occurs or not depends on the ability of a growing thrombus to resist flow forces exerted on its structure. This manuscript provides the first known in vivo measurement of how much stress a clot can withstand, before yielding to the surrounding blood flow. 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. 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. Therefore, drugs should be designed to target the shell selectively, while leaving the core intact to minimize excessive bleeding. 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. Thus, the findings presented herein will be beneficial to the understanding and treatment of heart attacks, strokes and hemophilia.
AB - Ischemia which leads to heart attacks and strokes is one of the major causes of death in the world. Whether an occlusion occurs or not depends on the ability of a growing thrombus to resist flow forces exerted on its structure. This manuscript provides the first known in vivo measurement of how much stress a clot can withstand, before yielding to the surrounding blood flow. 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. 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. Therefore, drugs should be designed to target the shell selectively, while leaving the core intact to minimize excessive bleeding. 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. Thus, the findings presented herein will be beneficial to the understanding and treatment of heart attacks, strokes and hemophilia.
KW - Blood
KW - Lattice Boltzmann method
KW - Microscopy
KW - Simulation
KW - Thrombus
KW - Yielding
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U2 - 10.1016/j.compbiomed.2019.01.001
DO - 10.1016/j.compbiomed.2019.01.001
M3 - Article
C2 - 30660757
AN - SCOPUS:85060012587
SN - 0010-4825
VL - 106
SP - 1
EP - 11
JO - Computers in Biology and Medicine
JF - Computers in Biology and Medicine
ER -