Local Hemodynamic Conditions Associated with Focal Changes in the Intracranial Aneurysm Wall.

BACKGROUND AND PURPOSE: Aneurysm hemodynamics has been associated with wall histology and inflammation. We investigated associations between local hemodynamics and focal wall changes visible intraoperatively. MATERIALS AND METHODS: Computational fluid dynamics models were constructed from 3D images of 65 aneurysms treated surgically. Aneurysm regions with different visual appearances were identified in intraoperative videos: 1) "atherosclerotic" (yellow), 2) "hyperplastic" (white), 3) "thin" (red), 4) rupture site, and 5) "normal" (similar to parent artery), They were marked on 3D reconstructions. Regional hemodynamics was characterized by the following: wall shear stress, oscillatory shear index, relative residence time, wall shear stress gradient and divergence, gradient oscillatory number, and dynamic pressure; these were compared using the Mann-Whitney test. RESULTS: Hyperplastic regions had lower average wall shear stress (P = .005) and pressure (P = .009) than normal regions. Flow conditions in atherosclerotic and hyperplastic regions were similar but had higher average relative residence time (P = .03) and oscillatory shear index (P = .04) than thin regions. Hyperplastic regions also had a higher average gradient oscillatory number (P = .002) than thin regions. Thin regions had lower average relative residence time (P < .001), oscillatory shear index (P = .006), and gradient oscillatory number (P < .001) than normal regions, and higher average wall shear stress (P = .006) and pressure (P = .009) than hyperplastic regions. Thin regions tended to be aligned with the flow stream, while atherosclerotic and hyperplastic regions tended to be aligned with recirculation zones. CONCLUSIONS: Local hemodynamics is associated with visible focal wall changes. Slow swirling flow with low and oscillatory wall shear stress was associated with atherosclerotic and hyperplastic changes. High flow conditions prevalent in regions near the flow impingement site characterized by higher and less oscillatory wall shear stress were associated with local "thinning" of the wall.

Angioarchitectures and Hemodynamic Characteristics of Posterior Communicating Artery Aneurysms and Their Association with Rupture Status.

BACKGROUND AND PURPOSE: Intracranial aneurysms originating at the posterior communicating artery are known to have high rupture risk compared with other locations. We tested the hypothesis that different angioarchitectures (ie, branch point configuration) of posterior communicating artery aneurysms are associated with aneurysm hemodynamics, which in turn predisposes aneurysms to rupture. MATERIALS AND METHODS: A total of 313 posterior communicating artery aneurysms (145 ruptured, 168 unruptured) were studied with image-based computational fluid dynamics. Aneurysms were classified into different angioarchitecture types depending on the location of the aneurysm with respect to parent artery bifurcation. Hemodynamic characteristics were compared between ruptured and unruptured aneurysms, as well as among aneurysms with different angioarchitectures. RESULTS: Angioarchitecture was associated with rupture (P = .003). Ruptured aneurysms had higher, more concentrated, and more oscillatory wall shear stress distributions (maximum wall shear stress, P < .001; shear concentration index, P < .001; mean oscillatory shear index, P < .001), stronger and more concentrated inflow jets (represented as Q, P = .01; inflow concentration index, P < .001), and more complex and unstable flow patterns (vortex core length, P < .001; proper orthogonal decomposition entropy, P < .001) compared with unruptured aneurysms. These adverse conditions were more common in aneurysms with bifurcation-type angioarchitectures compared with those with lateral or sidewall angioarchitectures. Interestingly, ruptured aneurysms also had lower normalized mean wall shear stress (P = .02) and minimum wall shear stress (P = .002) than unruptured aneurysms. CONCLUSIONS: High-flow intrasaccular hemodynamic characteristics, commonly found in bifurcation-type angioarchitectures, are associated with the posterior communicating artery aneurysm rupture status. These characteristics include strong and concentrated inflow jets, concentrated regions of elevated wall shear stress, oscillatory wall shear stress, lower normalized wall shear stress, and complex and unstable flow patterns.

Growth, phenotype, and function of human intestinal mast cells are tightly regulated by transforming growth factor beta1.

BACKGROUND AND AIMS: Transforming growth factor beta1 (TGF-beta1) is expressed in the healthy human intestine and controls mucosal immune responses and inflammation by regulating the function of lymphocytes, macrophages, dendritic cells, and eosinophils. Here, we asked whether human intestinal mast cells (MC) might also be subject to immunoregulation by TGF-beta1. METHODS: MC were isolated from the intestinal mucosa, purified, and cultured in vitro in the presence of stem cell factor (SCF) with or without TGF-beta1. Growth characteristics, phenotype, and immunological mediator release of MC were analysed by reverse transcription-polymerase chain reaction, flow cytometry, immunocytochemistry, western blot, and different immunoassays, respectively. RESULTS: TGF-beta1 dose dependently (ED50 approximately = 0.1 ng/ml) inhibited SCF dependent growth of human intestinal MC by both enhancing apoptosis and decreasing proliferation. In parallel, TGF-beta1 increased the percentage of connective tissue-type MC expressing tryptase and chymase while downregulating expression of the receptors for IgE and SCF. Furthermore, TGF-beta1 dramatically changed the profile of mediators released by MC following IgE receptor crosslinking. Release of histamine, cysteinyl-leukotrienes, and tumour necrosis factor alpha was strongly reduced whereas prostaglandin D2 generation and cyclooxygenase 1 and 2 expression were upregulated by TGF-beta1. CONCLUSIONS: Our data indicate that TGF-beta1 acts as a novel potent inhibitor and modulator of human intestinal MC effector functions. The change in MC mediator release profile and protease expression induced by TGF-beta1 might be of relevance for the control of MC associated disorders of the intestine such as allergic reactions, Crohn's disease, irritable bowel syndrome, and parasitic infection.