Willerson Center for Cardiovascular Modeling and Simulation, Oden Institute for Computational Engineering and Sciences, The University of Texas at Austin, Austin, TX, 78712, USA.
Center for Electron Microscopy and Analysis, The Ohio State University, Columbus, OH, 43210, USA.
Sci Rep. 2023 Aug 8;13(1):12852. doi: 10.1038/s41598-023-40158-w.
Genetically modified mouse models provide a versatile and efficient platform to extend our understanding of the underlying disease processes and evaluate potential treatments for congenital heart valve diseases. However, applications have been limited to the gene and molecular levels due to the small size of murine heart valves, which prohibits the use of standard mechanical evaluation and in vivo imaging methods. We have developed an integrated imaging/computational mechanics approach to evaluate, for the first time, the functional mechanical behavior of the murine pulmonary heart valve (mPV). We utilized extant mPV high resolution µCT images of 1-year-old healthy C57BL/6J mice, with mPVs loaded to 0, 10, 20 or 30 mmHg then chemically fixed to preserve their shape. Individual mPV leaflets and annular boundaries were segmented and key geometric quantities of interest defined and quantified. The resulting observed inter-valve variations were small and consistent at each TVP level. This allowed us to develop a high fidelity NURBS-based geometric model. From the resultant individual mPV geometries, we developed a mPV shape-evolving geometric model (SEGM) that accurately represented mPV shape changes as a continuous function of transvalvular pressure. The SEGM was then integrated into an isogeometric finite element based inverse model that estimated the individual leaflet and regional mPV mechanical behaviors. We demonstrated that the mPV leaflet mechanical behaviors were highly anisotropic and nonlinear, with substantial leaflet and regional variations. We also observed the presence of strong axial mechanical coupling, suggesting the important role of the underlying collagen fiber architecture in the mPV. When compared to larger mammalian species, the mPV exhibited substantially different mechanical behaviors. Thus, while qualitatively similar, the mPV exhibited important functional differences that will need to accounted for in murine heart valve studies. The results of this novel study will allow detailed murine tissue and organ level investigations of semi-lunar heart valve diseases.
基因修饰小鼠模型为深入了解潜在的疾病发生机制并评估先天性心脏瓣膜疾病的潜在治疗方法提供了一个多功能且高效的平台。然而，由于鼠类心脏瓣膜体积较小，限制了标准机械评估和体内成像方法的应用，因此其应用仅限于基因和分子水平。我们开发了一种集成的成像/计算力学方法，首次评估了鼠类肺动脉瓣（mPV）的功能机械行为。我们利用 1 岁健康 C57BL/6J 小鼠的现存 mPV 高分辨率 μCT 图像，将 mPV 加载至 0、10、20 或 30mmHg，然后进行化学固定以保持其形状。对个体 mPV 瓣叶和瓣环边界进行分割，并定义和量化感兴趣的关键几何量。在每个 TVP 水平下，观察到的瓣间变化都很小且一致。这使我们能够开发出一种高精度的 NURBS 几何模型。从得到的各个 mPV 几何形状中，我们开发了一个 mPV 形状演变几何模型（SEGM），该模型可以准确地表示 mPV 形状随跨瓣压的连续变化。然后，SEGM 被集成到基于等几何的有限元反演模型中，该模型估计了单个瓣叶和区域性 mPV 的力学行为。我们证明了 mPV 瓣叶的力学行为具有高度各向异性和非线性，并且瓣叶和区域性变化很大。我们还观察到存在很强的轴向力学耦合，这表明潜在的胶原纤维结构在 mPV 中起着重要作用。与较大的哺乳动物相比，mPV 表现出明显不同的力学行为。因此，尽管定性上相似，但 mPV 表现出重要的功能差异，需要在鼠类心脏瓣膜研究中加以考虑。这项新颖研究的结果将允许对半月形心脏瓣膜疾病进行详细的鼠类组织和器官水平研究。
