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  1. Osteoarthritis of the knee is increasingly prevalent as our population ages, representing an increasing financial burden, and severely impacting quality of life. The invasiveness of in vivo procedures and the high cost of cadaveric studies has left computational tools uniquely suited to study knee biomechanics. Developments in deep learning have great potential for efficiently generating large-scale datasets to enable researchers to perform population-sized investigations, but the time and effort associated with producing robust hexahedral meshes has been a limiting factor in expanding finite element studies to encompass a population. Here we developed a fully automated pipeline capable of taking magnetic resonance knee images and producing a working finite element simulation. We trained an encoder-decoder convolutional neural network to perform semantic image segmentation on the Imorphics dataset provided through the Osteoarthritis Initiative. The Imorphics dataset contained 176 image sequences with varying levels of cartilage degradation. Starting from an open-source swept-extrusion meshing algorithm, we further developed this algorithm until it could produce high quality meshes for every sequence and we applied a template-mapping procedure to automatically place soft-tissue attachment points. The meshing algorithm produced simulation-ready meshes for all 176 sequences, regardless of the use of provided (manually reconstructed) or predicted (automatically generated) segmentation labels. The average time to mesh all bones and cartilage tissues was less than 2 min per knee on an AMD Ryzen 5600X processor, using a parallel pool of three workers for bone meshing, followed by a pool of four workers meshing the four cartilage tissues. Of the 176 sequences with provided segmentation labels, 86% of the resulting meshes completed a simulated flexion-extension activity. We used a reserved testing dataset of 28 sequences unseen during network training to produce simulations derived from predicted labels. We compared tibiofemoral contact mechanics between manual and automated reconstructions for the 24 pairs of successful finite element simulations from this set, resulting in mean root-mean-squared differences under 20% of their respective min-max norms. In combination with further advancements in deep learning, this framework represents a feasible pipeline to produce population sized finite element studies of the natural knee from subject-specific models. 
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  2. Abstract

    Neuromusculoskeletal (NMS) models can aid in studying the impacts of the nervous and musculoskeletal systems on one another. These computational models facilitate studies investigating mechanisms and treatment of musculoskeletal and neurodegenerative conditions. In this study, we present a predictive NMS model that uses an embedded neural architecture within a finite element (FE) framework to simulate muscle activation. A previously developed neuromuscular model of a motor neuron was embedded into a simple FE musculoskeletal model. Input stimulation profiles from literature were simulated in the FE NMS model to verify effective integration of the software platforms. Motor unit recruitment and rate coding capabilities of the model were evaluated. The integrated model reproduced previously published output muscle forces with an average error of 0.0435 N. The integrated model effectively demonstrated motor unit recruitment and rate coding in the physiological range based upon motor unit discharge rates and muscle force output. The combined capability of a predictive NMS model within a FE framework can aid in improving our understanding of how the nervous and musculoskeletal systems work together. While this study focused on a simple FE application, the framework presented here easily accommodates increased complexity in the neuromuscular model, the FE simulation, or both.

     
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  3. null (Ed.)
    Nuclear mechanics is emerging as a key component of stem cell function and differentiation. While changes in nuclear structure can be visually imaged with confocal microscopy, mechanical characterization of the nucleus and its sub-cellular components require specialized testing equipment. A computational model permitting cell-specific mechanical information directly from confocal and atomic force microscopy of cell nuclei would be of great value. Here, we developed a computational framework for generating finite element models of isolated cell nuclei from multiple confocal microscopy scans and simple atomic force microscopy (AFM) tests. Confocal imaging stacks of isolated mesenchymal stem cells were converted into finite element models and siRNA-mediated Lamin A/C depletion isolated chromatin and Lamin A/C structures. Using AFM-measured experimental stiffness values, a set of conversion factors were determined for both chromatin and Lamin A/C to map the voxel intensity of the original images to the element stiffness, allowing the prediction of nuclear stiffness in an additional set of other nuclei. The developed computational framework will identify the contribution of a multitude of sub-nuclear structures and predict global nuclear stiffness of multiple nuclei based on simple nuclear isolation protocols, confocal images and AFM tests. 
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