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In Vivo Three-Dimensional Geometric Reconstruction of the Mouse Aortic Heart Valve

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Abstract

Aortic valve (AV) disease is a common valvular lesion in the United States, present in about 5% of the population at age 65 with increasing prevalence with advancing age. While current replacement heart valves have extended life for many, their long-term use remains hampered by limited durability. Non-surgical treatments for AV disease do not yet exist, in large part because our understanding of AV disease etiology remains incomplete. The direct study of human AV disease remains hampered by the fact that clinical data is only available at the time of treatment, where the disease is at or near end stage and any time progression information has been lost. Large animal models, long used to assess replacement AV devices, cannot yet reproduce AV disease processes. As an important alternative mouse animal models are attractive for their ability to perform genetic studies of the AV disease processes and test potential pharmaceutical treatments. While mouse models have been used for cellular and genetic studies of AV disease, their small size and fast heart rates have hindered their use for tissue- and organ-level studies. We have recently developed a novel ex vivo micro-CT-based methodology to 3D reconstruct murine heart valves and estimate the leaflet mechanical behaviors (Feng et al. in Sci Rep 13(1):12852, 2023). In the present study, we extended our approach to 3D reconstruction of the in vivo functional murine AV (mAV) geometry using high-frequency four-dimensional ultrasound (4DUS). From the resulting 4DUS images we digitized the mAV mid-surface coordinates in the fully closed and fully opened states. We then utilized matched high-resolution µCT images of ex vivo mouse mAV to develop mAV NURBS-based geometric model. We then fitted the mAV geometric model to the in vivo data to reconstruct the 3D in vivo mAV geometry in the closed and open states in n = 3 mAV. Results demonstrated high fidelity geometric results. To our knowledge, this is the first time such reconstruction was ever achieved. This robust assessment of in vivo mAV leaflet kinematics in 3D opens up the possibility for longitudinal characterization of murine models that develop aortic valve disease.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgments

This work was supported by the National Institutes of Health Grant HL142504.

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Authors and Affiliations

  1. Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA

    Daniel P. Gramling, Aletea L. van Veldhuisen, Frederick W. Damen & Craig J. Goergen

  2. Department of Pediatrics, Medical College of Wisconsin, Herma Heart Institute, Children’s Wisconsin Milwaukee, Milwaukee, WI, USA

    Kaitlyn Thatcher & Joy Lincoln

  3. Center for Electron Microscopy and Analysis, The Ohio State University, Columbus, OH, USA

    Felix Liu & David McComb

  4. Tissue Engineering and Surgical Research, Nationwide Children’s Hospital, Columbus, OH, USA

    Christopher K. Breuer

  5. Department of Biomedical Engineering, James T. Willerson Center for Cardiovascular Modeling and Simulation, Oden Institute for Computational Engineering and Sciences, The University of Texas at Austin, Austin, TX, USA

    Michael S. Sacks

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  1. Daniel P. Gramling
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Correspondence to Michael S. Sacks.

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Craig Goergen is a paid consultant of FUJIFILM VisualSonics Inc. The other authors declare no conflict of interest.

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Gramling, D.P., van Veldhuisen, A.L., Damen, F.W. et al. In Vivo Three-Dimensional Geometric Reconstruction of the Mouse Aortic Heart Valve. Ann Biomed Eng (2024). https://doi.org/10.1007/s10439-024-03555-4

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