Logistics of Building Virtual Specimens for In Silico Biomechanics

Ahmet Erdemir1,2, Tara Bonner1,3, Snehal Chokhandre1,2, Robb Colbrunn1,3, Benjamin Landis1,2, Erica Morrill1,2, Tammy Owings1, Tyler Schimmoeller1,2

1Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic

2Computational Biomodeling (CoBi) Core, Lerner Research Institute, Cleveland Clinic

3BioRobotics and Mechanical Testing Core, Lerner Research Institute, Cleveland Clinic

Introduction: In medicine, computational modeling and simulation enables scientific discovery, facilitates engineering innovation, and supports clinical care. When virtual specimens are available, simulation-based explorations provide the means to understand healthy function of the human body and consequences of diseases, and to predict outcome of interventions. Virtual specimens can lead to virtual subjects, patients, and populations to enable in silico trials and for the delivery of precision medicine. In biomechanics, virtual specimens require authentic representation of their anatomical features and physiological properties to perform simulations under meaningful loading conditions. When reliable, they can replace actual specimens to reduce human subjects testing, cadaver experimentation, and animal studies. However, development of virtual specimens is prohibitively challenging when the added goal is to provide data and methodologies in an open, accessible way. This study summarizes strategies that have been adopted in our recent projects [1,2] to overcome the logistical burden of development, dissemination, and support of virtual specimens.

Materials and Methods: Strategies for building models of the knee [2] and layered-tissue structures of musculoskeletal extremities [1] are documented in their respective web sites as part of an open science driven approach. These are synthesized and provided in this document in summary form.

Results and Discussion: The activities to build virtual specimens result in heterogeneous information that need to be curated, managed, and disseminated. For any task throughout the lifecycle of virtual specimens, specifications for the task are designed and documented first. Development of virtual specimens involves data collection, data analysis, data management, model development, model management, simulations, and simulation management. Data collection is intended to support authenticity of the virtual specimens. It spans imaging for reconstruction of specimen-specific anatomy, tissue testing for specimen-specific material properties, and joint or organ level loading for specimen-specific validation studies. Data analysis steps bring raw data in a form usable for modeling and simulation, e.g., generation of meshes, identification of constitutive parameters, etc. For various development stages, automation can increase efficiency and reduce user/developer error. For example, data analysis scripts can extract model parameters directly from raw data. Model development steps can also be streamlined, i.e., surface representations of tissue components can be meshed and assembled, connections and interactions can be defined based on proximity analysis, and model files can be exported in various simulation software formats. Quality assurance of data is established by reproducibility tests at the tissue or organ level. Similar strategies for modeling quantify uncertainties in virtual representation of individual tissue components, e.g., their geometry. Version control is implemented at all stages. Data, model, and simulation management platforms and workflows associate heterogeneous data types and support traceability of models and derivative data to their origin. Document generation (user or developer), document management, and dissemination of data and models provide support for user engagement. An open development approach and free and open source dissemination ensure utmost outreach to the biomedical community. The use of free and open source software tools for data analysis and model generation, software agnostic approach for virtual representation, and cloud computing support enable anyone to build upon the capabilities of virtual specimens.

Translational Impact: Sample strategies to tackle logistical challenges of building virtual specimens can assist the biomechanics community in effective utilization of existing models and development of organ representations.

Acknowledgments: This study has been supported by USAMRMC (W81XWH-15-1-0232) [1] and NIGMS, NIH (R01GM104139) [2]. The views, opinions and/or findings contained in this document are those of the authors and do not necessarily reflect the views of the funding agencies. The authors are thankful for contributions of all past and current collaborators, see project sites for more details.

References: [1] Reference Models for Multi-Layer Tissue Structures @ https://simtk.org/projects/multis. [2] Open Knee(s): Virtual Biomechanical Representations of the Knee Joint @ https://simtk.org/projects/openknee.