Division of Applied Mathematics, Brown University, Providence, RI, 02912, USA.
Department of Biomedical Engineering, Yale University, New Haven, CT, 06520, USA.
Sci Rep. 2018 Feb 6;8(1):2515. doi: 10.1038/s41598-018-20603-x.
Aortic dissection is a pathology that manifests due to microstructural defects in the aortic wall. Blood enters the damaged wall through an intimal tear, thereby creating a so-called false lumen and exposing the blood to thrombogenic intramural constituents such as collagen. The natural history of this acute vascular injury thus depends, in part, on thrombus formation, maturation, and possible healing within the false lumen. A key question is: Why do some false lumens thrombose completely while others thrombose partially or little at all? An ability to predict the location and extent of thrombus in subjects with dissection could contribute significantly to clinical decision-making, including interventional design. We develop, for the first time, a data-driven particle-continuum model for thrombus formation in a murine model of aortic dissection. In the proposed model, we simulate a final-value problem in lieu of the original initial-value problem with significantly fewer particles that may grow in size upon activation, thus representing the local concentration of blood-borne species. Numerical results confirm that geometry and local hemodynamics play significant roles in the acute progression of thrombus. Despite geometrical differences between murine and human dissections, mouse models can provide considerable insight and have gained popularity owing to their reproducibility. Our results for three classes of geometrically different false lumens show that thrombus forms and extends to a greater extent in regions with lower bulk shear rates. Dense thrombi are less likely to form in high-shear zones and in the presence of strong vortices. The present data-driven study suggests that the proposed model is robust and can be employed to assess thrombus formation in human aortic dissections.
主动脉夹层是一种由于主动脉壁的微观结构缺陷而表现出的病理学。血液通过内膜撕裂进入受损的壁,从而形成所谓的假腔,并使血液暴露于血栓形成的壁内成分,如胶原蛋白。因此,这种急性血管损伤的自然史部分取决于假腔内的血栓形成、成熟和可能的愈合。一个关键问题是:为什么有些假腔完全血栓形成,而有些则部分或几乎不血栓形成?能够预测夹层患者中血栓的位置和程度,可能会对临床决策,包括介入设计产生重大影响。我们首次为主动脉夹层的鼠模型开发了一个基于数据的血栓形成颗粒连续体模型。在所提出的模型中,我们模拟了一个最终值问题,而不是具有明显更多可能在激活时增大的粒子的原始初始值问题,从而代表了血液传播物质的局部浓度。数值结果证实,几何形状和局部血液动力学在血栓的急性进展中起着重要作用。尽管鼠类和人类夹层之间存在几何差异,但由于其可重复性,鼠类模型可以提供相当大的见解,并已变得流行。我们对三类几何形状不同的假腔的结果表明,在低体剪切率区域,血栓形成和扩展的程度更大。在高剪切率区域和存在强涡流的情况下,致密血栓形成的可能性较小。本数据驱动研究表明,所提出的模型是稳健的,可以用于评估人类主动脉夹层中的血栓形成。