Laminar axially directed blood flow promotes blood clot dissolution: Mathematical modeling verified by MR microscopy

Abstract

Understandig process of thrombolysis is a key for a corresponding medical treatment. Thrombolysis of nonocclusive blood clots is significantly accelerated by axially directed blood plasma flow. When fast blood flow occurs, the increase of the dissolution rate is too big that it could be explained just by better permeation of the thrombolytic agent into the clot and more efficient biochemical degradation. Viscous forces caused by shearing of blood play an essential role in addition to the known biochemical fibrinolytic reactions. We developed an analytical mathematical model based on a hypothesis that clot dissolution dynamics is proportional to the power of the blood plasma flow dissipating along the clot. The model assumes cylindrical non-occlusive blood clots with centrally placed flow channel and the flow is assumed laminar at a constant rate all times during dissolution. Effects of sudden constriction on the flow and its impact on the dissolution rate are considered as well. The model of clot dissolution was verified experimentally by dynamic magnetic resonance (MR) microscopy in in-vitro circulation system containing plasma with a magnetic resonance imaging contrast agent and recombinant tissue-type plasminogen activator (rt-PA). Sequences of dynamically acquired 3D low resolution MR images of entire clots and 2D high resolution MR images of clots in an axial cross-section were used to evaluate the dissolution model by fitting it to the experimental data. The experimental data fitted well to the model, and confirmed our hypothesis.