Unravelling the fundamentals of the blood flow dynamics in the bone and bone marrow vasculature of long bones using combined 3D imaging and computational modelling approach

Details

Supervisors

Kerckhofs, Greet

Faculty

Ecole polytechnique de Louvain

Degree label

Master [120] : ingénieur civil biomédical

Abstract

Blood is a complex fluid, which consists of blood plasma – a liquid comprised of water, small molecules and various proteins – and blood cells that supplies oxygen, nutrients and minerals to the different tissues in the human body. In the bone marrow compartment, this blood supply is particularly crucial due to the hematopoiesis process which takes place there. Yet, this process has been shown to decline with age and the reason therefore remains poorly understood but is thought to be tightly related with the functional organization and the blood flow dynamics of the microvascular network of the bone marrow. The purpose of this thesis is thus to study how changes in the microvascular structure of the bone marrow can affect the dynamics of blood flow and consequently the production of stem cells. First, a long literature review is made to study the physiology of the bone marrow. Then the different approaches developed in the past decades to model blood flow is reviewed in order to see which is the most appropriate one for the microvascular structure of the bone marrow. Indeed, on the macroscopic level, Computational Fluid Dynamics (CFD) which describes blood as a continuum fluid using constitutive equations for the fluid properties has been very successful but when it comes to the microscopic level this approach is not the most appropriate because of the particulate nature of blood flow in small vessels (arterioles, capillaries, and venules). Mesoscopic models and simulation approaches, which describe blood as a suspension of soft, deformable particles or cells have been developed in recent years but are more computational and only local. Finally, 0D-modeling using electrical circuits is chosen due to its ease of implantation regarding to the complexity of the bone marrow microvasculature. Subsequently, an image processing routine to detect the different microvascular structures of the bone marrow in young and old mice is firstly developed after obtaining datasets from CE-CT imaging of two old and two young mice. Comparison between them shows the presence of a maze-like structure in young mice while this was not found in the old one. Also, more capillaries vessels were found in the middle region of old mice compare to the young ones. Thereafter, 0D young and old models using electrical circuits are developed from the previous analyses and mean blood velocities in the different regions of the bone marrow microvascular structure are computed. In the old mouse model, an abrupt change of blood velocity was observed in the capillaries mostly detected in the middle region while in the young one, no abrupt change was observed in the capillaries, which were mostly detected at the periphery of the marrow. As a conclusion, shifting of the angiogenesis process (physiological process through which new blood vessels are formed from pre-existing vessels) from the periphery to the center of the marrow seems to be correlated with a progressive degeneration of the maze-like structure found at the periphery of young mice. This shift has shown changes in term of mean blood velocity at a global scale and can be at the origin of a progressive decrease in the production of stem cells. But this assumption will still need to be demonstrated in further researches through local blood flow modeling and using more statistical data’s.