Predictive haemodynamics in a one-dimensional human carotid artery bifurcation. Part II: application to graft design

A Bayesian surrogate modelling technique is proposed that may be able to predict an optimal bypass graft configuration for patients suffering with stenosis in the internal carotid artery (ICA). At the outset, this statistical technique is considered as a means for identifying key geometric parameters influencing haemodynamics in the human carotid bifurcation. This methodology uses a design of experiments (DoE) technique to generate candidate geometries for flow analysis. A pulsatile one dimensional Navier-Stokes solver incorporating fluid-wall interactions for a Newtonian fluid which predicts pressure and flow in the carotid bifurcation (comprising a stenosed segment in the internal carotid artery) is used for the numerical simulations. Two metrics, pressure variation factor (PVF) and maximum pressure (pm) are employed to directly compare the global and local effects, respectively, of variations in the geometry. The values of PVF and pm are then used to construct two Bayesian surrogate models. These models are statistically analysed to visualise how each geometric parameter influences PVF and pm. Percentage of stenosis is found to influence these pressure based metrics more than any other geometric parameter. Later, we identify bypass grafts with optimal geometric and material properties which have low values of PVF on five test cases with 70%, 75%, 80%, 85% and 90% stenosis in the ICA, respectively

Sustained Ca2+ mobilizations: A quantitative approach to predict their importance in cell-cell communication and wound healing.

Epithelial wound healing requires the coordination of cells to migrate as a unit over the basement membrane after injury. To understand the process of this coordinated movement, it is critical to study the dynamics of cell-cell communication. We developed a method to characterize the injury-induced sustained Ca2+ mobilizations that travel between cells for periods of time up to several hours. These events of communication are concentrated along the wound edge and are reduced in cells further away from the wound. Our goal was to delineate the role and contribution of these sustained mobilizations and using MATLAB analyses, we determined the probability of cell-cell communication events in both in vitro models and ex vivo organ culture models. We demonstrated that the injury response was complex and represented the activation of a number of receptors. In addition, we found that pannexin channels mediated the cell-cell communication and motility. Furthermore, the sustained Ca2+ mobilizations are associated with changes in cell morphology and motility during wound healing. The results demonstrate that both purinoreceptors and pannexins regulate the sustained Ca2+ mobilization necessary for cell-cell communication in wound healing