טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentMoiseyev Gilead
SubjectMesoscopic Simulation of Hemodynamically Induced Blood
Coagulation
DepartmentDepartment of Mechanical Engineering
Supervisor Professor Emeritus Pinhas Bar-Yoseph
Full Thesis textFull thesis text - English Version


Abstract

The purpose of this research was to develop a mesoscopic model of blood coagulation, which incorporates homodynamic effects with coagulation reactions into a fluid simulation model in a way which will allow for prediction of hemodynamically coagulation formation and growth. Such models could be used as an engineering tool for designing vascular implants such as stents, grafts and artificial valves, and intravascular procedures such as aneurysm coiling and vascular grafting. A key point in our work was to strive to a model which employs few or no fitting parameters, and to validate our model’s theoretical results against experimental data.

Our approach was to apply mesoscopic modeling on a simplified coagulation cascade. Current art use either bottom-up (multi-scale) methods based on modeling individual particles, or top-down (continuum) methods based on convection-reaction of continues distributions.  The proposed approach is a ‘middle-way’ between the two, so as the coagulation constituents (Platelets, Fibrin fibers, Thrombin molecules) are modeled as non-continues density populations, while their reactions are based on particle interactions. This allows for the advantages of top-down modeling while having the coagulation form as an emergent behavior from the particle interactions driving the coagulation process. The proposed coagulation model includes three basic interactions: Platelet activation, Platelet Tethering (deposition), and Fibrin Polymerization.  Each of those reactions was sub-modeled separately using the mesoscopic approach, and coupled together with a CFD platform and a fluid/solid interaction platform, they constitute the proposed coagulation model.

The model and its components are verified against both in-vitro and in-vivo data demonstrating its ability to accurately capture the complexities of Hemodynamic coagulation growth. We demonstrate our results to be in a remarkable agreement with the experimental results reported by (Nesbitt et al, Nature 2009), both qualitatively and quantitatively. While quantitative comparison to in-vivo results is difficult, qualitatively our results are with good agreement and harmonious with the results obtained from the in vivo measurements (Wottoon et al, 2001).

These comparisons successfully demonstrate that the mesoscopic approach and cascade simplification on which the proposed model are based are successful in accurately capturing the physics of the coagulation process. Furthermore, analysis of the model results and detailed in the research provides insight into the conditions driving coagulation growth, the relations between the microscopic properties and how they are expressed in the macro scale, and how complex and differing flow patterns effect the coagulation.