In Vivo Measurement of Blood Clot Mechanics from Computational Fluid Dynamics based on Intravital Microscopy Images

TL;DR

This study introduces a novel in vivo method to measure blood clot stresses using computational fluid dynamics based on microscopy images, revealing differences in core and shell deformation that inform targeted drug design.

Contribution

It provides the first in vivo measurement of clot yield stresses from 3D geometries derived from microscopy images, and establishes a foundation for a unified thrombogenesis theory.

Findings

The clot 'core' remains undeformed under flow.

The 'shell' of the clot is more prone to embolization.

A nondimensionalization relates clot mechanics to biology.

Abstract

Ischemia leading to heart attacks and strokes is the major cause of deaths in the world. Whether an occlusion occurs or not, depends on the ability of a growing thrombus to resist forces exerted on its structure. This manuscript provides the first known in vivo measurement of the stresses that clots can withstand, before yielding to the surrounding blood flow. Namely, Lattice-Boltzmann Method flow simulations are performed based on 3D clot geometries. The latter 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 latter is more prone to embolization. Hence, 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.