Purpose The growth or rupture of cerebral aneurysms is thought to be a complex arterial wall response caused by an interaction of biological and hemodynamic factors. Current approaches that analyze the effects of flow stress on vascular cells are limited by their simplistic design, lacking patient-specific vascular anatomic features that contribute to disease. In this study, we compare wall shear stress (WSS) acquired using 4D Flow MRA from a 3D printed model with patient-specific aneurysm to gene expression of endothelial cells attached inside the same vascular model.
Materials and methods Patient-specific vascular models were created from follow-up images in patients whose saccular aneurysms were confirmed to grow afterwards by CT angiography. The vascular models were connected to a flow-pump and a 4D Flow MRA was performed. WSS data was calculated from the acquisition and post-processed using a custom MATLAB environment. The same vascular models were coated with fibronectin and rotated in 3D with endothelium in culture incubator for cell lining. Viscosity-adjusted culture media was perfused using the same perfusion conditions with 4D Flow MRA. After perfusion, RNA was extracted from endothelial cells in the parent artery and the aneurysm and gene expression was examined using quantitative PCR (qPCR). In addition, the morphology of endothelial cells in specific regions of the model were observed with confocal microscopy.
Results Endothelial cells in growing regions with low wall shear within the aneurysm were irregular in shape and size and associated with up-regulation of inflammatory genes compared with cells in the parent artery that exhibited typical spindle shape and aligned with the directionality of flow.
Conclusions This research model enables a new approach to bridge the gap of biophysical flow phenomonology and the biological impact of complex flow patterns on endothelial cells using patient-derived imaging data. This approach is likely to be useful to determine flow-driven biological changes in vascular endothelium that contribute to aneurysm growth and rupture.
Disclosures N. Kaneko: None. S. Tateshima: None. M. Loecher: None. J. Villablanca: None. D. Chen: None. Y. Komuro: None. W. Chang: None. D. Ennis: None. F. Vinuela: None. G. Duckwiler: None. J. Hinman: None.
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