Multiple studies have demonstrated that the pathological geometries unique to each patient can affect the durability of mitral valve (MV) repairs. While computational modeling of the MV is a promising approach to improve the surgical outcomes, the complex MV geometry precludes use of simplified models. Moreover, the lack of complete in-vivo geometric information presents significant challenges in the development of patient-specific computational models. There is thus a need to determine the level of detail necessary for predictive MV models. To address this issue, we have developed a novel pipeline for building attribute-rich computational models of MV with varying fidelity directly from the in-vitro imaging data. The approach combines high-resolution geometric information from loaded and unloaded states to achieve a high level of anatomic detail, followed by mapping and parametric embedding of tissue attributes to build a high resolution, attribute-rich computational models. Subsequent lower resolution models were then developed, and evaluated by comparing the displacements and surface strains to those extracted from the imaging data. We then identified the critical levels of fidelity for building predictive MV models in the dilated and repaired states. We demonstrated that a model with a feature size of ~5 mm and mesh size of ~1 mm was sufficient to predict the overall MV shape, stress, and strain distributions with high accuracy. However, we also noted that more detailed models were found to be needed to simulate microstructural events. We conclude that the developed pipeline enables sufficiently complex models for biomechanical simulations of MV in normal, dilated, repaired states.

The complexities of modern biomedicine are rapidly increasing. Thus, modeling and simulation have become increasingly important as a strategy to understand and predict the trajectory of pathophysiology, disease genesis, and disease spread in support of clinical and policy decisions. In such cases, inappropriate or ill-placed trust in the model and simulation outcomes may result in negative outcomes, and hence illustrate the need to formalize the execution and communication of modeling and simulation practices. Although verification and validation have been generally accepted as significant components of a model’s credibility, they cannot be assumed to equate to a holistic credible practice, which includes activities that can impact comprehension and in-depth examination inherent in the development and reuse of the models. For the past several years, the Committee on Credible Practice of Modeling and Simulation in Healthcare, an interdisciplinary group seeded from a U.S. interagency initiative, has worked to codify best practices. Here, we provide Ten Rules for credible practice of modeling and simulation in healthcare developed from a comparative analysis by the Committee’s multidisciplinary membership, followed by a large stakeholder community survey. These rules establish a unified conceptual framework for modeling and simulation design, implementation, evaluation, dissemination and usage across the modeling and simulation life-cycle. While biomedical science and clinical care domains have somewhat different requirements and expectations for credible practice, our study converged on rules that would be useful across a broad swath of model types. In brief, the rules are: (1) Define context clearly. (2) Use contextually appropriate data. (3) Evaluate within context. (4) List limitations explicitly. (5) Use version control. (6) Document appropriately. (7) Disseminate broadly. (8) Get independent reviews. (9) Test competing implementations. (10) Conform to standards. Although some of these are common sense guidelines, we have found that many are often missed or misconstrued, even by seasoned practitioners. Computational models are already widely used in basic science to generate new biomedical knowledge. As they penetrate clinical care and healthcare policy, contributing to personalized and precision medicine, clinical safety will require established guidelines for the credible practice of modeling and simulation in healthcare.

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Mitral valve (MV) closure depends upon the proper function of each component of the valve apparatus, which includes the annulus, leaflets, and chordae tendineae (CT). Geometry plays a major role in MV mechanics and thus highly impacts the accuracy of computational models simulating MV function and repair. While the physiological geometry of the leaflets and annulus have been previously investigated, little effort has been made to quantitatively and objectively describe CT geometry. The CT constitute a fibrous tendon-like structure projecting from the papillary muscles (PMs) to the leaflets, thereby evenly distributing the loads placed on the MV during closure. Because CT play a major role in determining the shape and stress state of the MV as a whole, their geometry must be well characterized. In the present work, a novel and comprehensive investigation of MV CT geometry was performed to more fully quantify CT anatomy. In vitro micro-tomography 3D images of ovine MVs were acquired, segmented, then analyzed using a curve-skeleton transform. The resulting data was used to construct B-spline geometric representations of the CT structures, enriched with a continuous field of cross-sectional area (CSA) data. Next, Reeb graph models were developed to analyze overall topological patterns, along with dimensional attributes such as segment lengths, 3D orientations, and CSA. Reeb graph results revealed that the topology of ovine MV CT followed a full binary tree structure. Moreover, individual chords are mostly planar geometries that together form a 3D load-bearing support for the MV leaflets. We further demonstrated that, unlike flow-based branching patterns, while individual CT branches became thinner as they propagated further away from the PM heads towards the leaflets, the total CSA almost doubled. Overall, our findings indicate a certain level of regularity in structure, and suggest that population-based MV CT geometric models can be generated to improve current MV repair procedures.