Numerical and in vitro experimental study of arterial deformation and buckling under hypertension and atherosclerotic conditions

Cardiovascular diseases remain the major cause of mortality worldwide. Pathologies of the vasculature such as atherosclerosis are often related to biochemical and genetic factors as well as mechanical effects that strongly change the function and shape of arteries. The present work is part of a general research project which aims to better understand the mechanical mechanisms responsible for atherosclerotic plaque formation and rupture. The chosen approach is to use numerical fluidstructure interaction (FSI) methods to study the relative influence of hemodynamic parameters on the structural stresses generated on plaques. To this aim, a numerical study of a simplified straight vessel exposed to lumen pressure was investigated under quiescent and steady flow conditions. As the internal pressure or the steady velocity increases, the vessel buckles lead-ing to a non-linear large deformation behaviour. The results have been validated using theoretical predictions for the buckling thresholds. Further studies on idealised cardiovascular conditions such as stenosis (i.e., lumen constriction) or aneurysm like (i.e., arterial wall expansion) formation have also been performed

Wake states of a submerged oscillating cylinder and of a cylinder beneath a free-surface

Abstract not availabl

Wake states of a submerged oscillating cylinder and of a cylinder beneath a free-surface

Abstract not availabl

Methods to determine the lagrangian shear experienced by platelets during thrombus growth

Platelets can become activated in response to changes in flow-induced shear; however, the underlying molecular mechanisms are not clearly understood. Here we present new techniques for experimentally measuring the flow-induced shear rate experienced by platelets prior to adhering to a thrombus. We examined the dynamics of blood flow around experimentally grown thrombus geometries using a novel combination of experimental (ex vivo) and numerical (in silico) methodologies. Using a microcapillary system, platelet aggregate formation was analysed at elevated shear rates in the presence of coagulation inhibitors, where thrombus formation is predominantly platelet-dependent. These approaches permit the resolution and quantification of thrombus parameters at the scale of individual platelets (2 μm) in order to quantify real time thrombus development. Using our new techniques we can correlate the shear rate experienced by platelets with the extent of platelet adhesion and aggregation. The techniques presented offer the unique capacity to determine the flow properties for a temporally evolving thrombus field in real time

Functional imaging to understand biomechanics : a critical tool for the study of biology, pathology and the development of pharmacological solutions

We present four case studies of the literature discussing the effects of physical forces on biological function. While the field of biomechanics has existed for many decades, it may be considered by some a poor cousin to biochemistry and other traditional fields of medical research. In these case studies, including cardiovascular and respiratory systems, we demonstrate that, in fact, many systems historically believed to be controlled by biochemistry are dominated by biomechanics. We discuss both the previous paradigms that have advanced research in these fields and the changing paradigms that will define the progressions of these fields for decades to come. In the case of biomechanical effects of flowing blood on the endothelium, this has been well understood for decades. In the cases of platelet activation and liquid clearance from the lungs during birth, these discoveries are far more recent and perhaps not as universally accepted. While only a few specific examples are examined here, it is clear that not enough attention is paid to the possible mechanical links to biological function. The continued development of these research areas, with the inclusion of physical effects, will hopefully provide new insight into disease development, progression, diagnosis and effective therapies

Novel stenotic microchannels to study thrombus formation in shear gradients:influence of shear forces and human platelet-related factors

Thrombus formation in hemostasis or thrombotic disease is initiated by the rapid adhesion, activation, and aggregation of circulating platelets in flowing blood. At arterial or pathological shear rates, for example due to vascular stenosis or circulatory support devices, platelets may be exposed to highly pulsatile blood flow, while even under constant flow platelets are exposed to pulsation due to thrombus growth or changes in vessel geometry. The aim of this study is to investigate platelet thrombus formation dynamics within flow conditions consisting of either constant or variable shear. Human platelets in anticoagulated whole blood were exposed ex vivo to collagen type I-coated microchannels subjected to constant shear in straight channels or variable shear gradients using different stenosis geometries (50%, 70%, and 90% by area). Base wall shears between 1800 and 6600 s−1, and peak wall shears of 3700 to 29,000 s−1 within stenoses were investigated, representing arterial-pathological shear conditions. Computational flow-field simulations and stenosis platelet thrombi total volume, average volume, and surface coverage were analysed. Interestingly, shear gradients dramatically changed platelet thrombi formation compared to constant base shear alone. Such shear gradients extended the range of shear at which thrombi were formed, that is, platelets became hyperthrombotic within shear gradients. Furthermore, individual healthy donors displayed quantifiable differences in extent/formation of thrombi within shear gradients, with implications for future development and testing of antiplatelet agents. In conclusion, here, we demonstrate a specific contribution of blood flow shear gradients to thrombus formation, and provide a novel platform for platelet functional testing under shear conditions.We acknowledge financial support from the National Health and Medical Research Council, Australia (APP1147214, APP1042865, APP1126536) and The Australian Research Council (DP190100039)

Time-corrected thrombus reconstruction process.

<p><b>(</b>a) Image metadata showing microscope stage position over time. (b) Individual slices have original acquisition times assigned from metadata. Acquired confocal images are in black; morphed intermediate images are in blue (c). Slices corresponding to the 149-second timepoint are extracted and stacked vertically forming an instantaneous z-stack which is reconstructed (d) to produce the thrombus field at 149 seconds.</p

Comparison between real-time surfaces and time skewed surfaces.

<p>Comparison between ellipsoid reconstructions constructed using (a) real-time corrected ellipse slices and (b) ellipse slices derived from time skewed slices. (c) Comparison between time stack thrombus reconstruction (top) and real-time thrombus reconstruction (bottom) mirrored through the central plane. </p