Functional mechanical behavior of the murine pulmonary heart valve.
Functional mechanical behavior of the murine pulmonary heart valve.
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DOI：
10.1038/s41598-023-40158-w
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发表时间：
2023-08-08
影响因子：
4.6
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中科院分区：
文献类型：
--
作者：
转基因小鼠模型提供了一个通用和有效的平台，以扩大我们对潜在疾病过程的理解，并评估先天性心脏瓣膜疾病的潜在治疗方法。然而，由于小鼠心脏瓣膜的尺寸较小，其应用一直局限于基因和分子水平，这使得标准的机械评估和活体成像方法的使用受到限制。我们首次开发了一种集成的成像/计算力学方法来评估小鼠肺瓣膜(MPV)的功能力学行为。我们利用现有的1岁健康C57BL/6J小鼠的MPV高分辨率µCT图像，将MPV加载到0、10、20或30毫米汞，然后进行化学固定以保持其形状。对单个MPV小叶和环形边界进行了分割，并定义和量化了感兴趣的关键几何量。由此观察到的瓣膜间变化很小，并且在每个TVP水平上都是一致的。这使得我们能够开发出高保真的基于NURBS的几何模型。从得到的单个MPV几何形状，我们发展了一个MPV形状演变几何模型(SEGM)，它准确地将MPV形状变化描述为跨瓣膜压力的连续函数。然后将SEGM集成到基于等距有限元的逆模型中，该模型估计了单个叶和局部MPV的力学行为。我们证明了MPV小叶的力学行为是高度各向异性和非线性的，具有很大的小叶和区域差异。我们还观察到了强烈的轴向机械耦合的存在，这表明潜在的胶原纤维结构在MPV中扮演着重要的角色。与较大的哺乳动物物种相比，MPV表现出显著不同的机械行为。因此，虽然在性质上相似，但MPV显示出重要的功能差异，这需要在小鼠心脏瓣膜研究中加以说明。这项新研究的结果将允许对半月型心脏瓣膜疾病的小鼠组织和器官水平进行详细的研究。
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.
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影响因子：
4.6
作者：
Joyce, Erinn M.;Liao, Jun;Schoen, Frederick J.;Mayer, John E., Jr.;Sacks, Michael S.
通讯作者：
Sacks, Michael S.
影响因子：
3.8
作者：
Amini, Rouzbeh;Eckert, Chad E.;Koomalsingh, Kevin;McGarvey, Jeremy;Minakawa, Masahito;Gorman, Joseph H.;Gorman, Robert C.;Sacks, Michael S.
通讯作者：
Sacks, Michael S.
影响因子：
4.9
作者：
Martin, Caitlin;Sun, Wei
通讯作者：
Sun, Wei
影响因子：
2.4
作者：
Rego, Bruno V.;Sacks, Michael S.
通讯作者：
Sacks, Michael S.
影响因子：
2.2
作者：
Ruff, J;Wiesmann, F;Haase, A
通讯作者：
Haase, A