Okay, next we'll hear Dr. Malik about why bifurcation morphology induces aneurysmogenic high positive wall shear stress gradient at the apex independent of flow rate. Great, thank you very much. We've previously shown that aneurysms at the basilar artery were associated with a wide angle at the basilar bifurcation. Looking at controls compared to patients with aneurysm in other locations and patients with basilar aneurysm, you can see that patients with basilar aneurysm had a much wider bifurcation angle with the intermediate between. This finding was also duplicated in patients with middle cerebral artery bifurcations where aneurysms were found to be associated with a wider bifurcation angle. Again, this is the total angle of the bifurcation is much higher in patients harboring aneurysms compared to controls. In fact, looking just at the bifurcation angle, you can have an AUC of greater than 0.85% at predicting the presence of an aneurysm. We sought to look at the hemodynamic forces that may be involved with this phenomenon. Endothelial cells are known to be regulated by shear, but they're also regulated by something called shear gradient, which is a spatial change in the shear stress. So when you have a negative shear gradient in this region, you see the endothelial cell are quiescent. When you have a positive shear gradient, the endothelial cells migrate and you get aneurysmogenic changes underneath that layer. This was also shown to be the case in animal models by Hui-Meng and a colleague's group in Buffalo. So we sought to do a computation fluid dynamic simulation using parametric modeling of the bifurcation using both symmetric, asymmetric, and symmetric with a parent vessel curvature and evaluated the shear stress gradient and the shear stress at the apex. And we identified a threshold of around 85 degrees, where in fact you'll see that there is a beginning of an appearance of the positive shear gradient at that level and at wider bifurcations. So if you focus on the shear gradient, you can see that at 0.85, which is the green, you start seeing positive shear gradients, which increase further at 120 and 180 degrees. And those are actually negative for smaller bifurcations. For asymmetric bifurcations, we saw that that positive shear gradient is found on the branch that has a wider angle that you see here, and it remains negative on the narrow angle. When we took a parent vessel that was in fact curved instead of straight, we can see that that caused a protection of the narrow angle. I'm sorry, it caused a protection of the wider angle and caused an increase in the sensitivity of the narrower branch. So now we could start seeing positive shear gradient at even smaller angles than otherwise seen in a straight parent vessel. This is also seen in acute actual patient aneurysmal bifurcations where the aneurysm is removed and the gradients are evaluated at the apex. And you can see that we actually have positive shear gradients in those as well. So in conclusion, apical shear forces and spatial gradients are highly dependent on bifurcation angle and inflow vessel geometry. The development of the aneurysmogenic positive wall shear gradient appears to happen at or greater than 85 degrees, and it provides a mechanotransduction link for the association of white bifurcations and aneurysm development. These results suggest possible therapeutic strategies aimed at altering both the unfavorable geometry, which we've previously shown can be done with Y stenting or single stenting, and also offer the opportunity to decipher the molecular endothelial response underlying these changes. Thank you. Any other questions? Thank you very much. This concludes this session.

bifurcation morphology

aneurysm development

shear stress

shear gradient

therapeutic strategies