Given the strong ties to data sharing and the responsible use of resources, reproducibility of modeling and simulation practice is of paramount importance in science. Computational models in orthopedics provide insight into healthy and injured joint mechanics and can inform clinical decision-making. The KneeHub project investigated the influence of modelers' decisions and thus their "art" in simulation and modeling; five teams developed and calibrated knee models using the same experimental data. Model benchmarking evaluated the predictive ability of the models under loading scenarios that were not considered in the development and calibration process. The objective of this study was to evaluate the accuracy of predictions of knee-specific joint biomechanics for benchmark scenarios of simulating a resected anterior cruciate ligament (ACL) using models of one knee and a combined pivot shift loading using models of another knee. The models predicted the major trends in kinematics and kinetics; however, differences were observed in comparison to experimental data and between teams. Model-to-experiment root-mean-square (RMS) errors were up to 6.6±2.4 mm in anterior-posterior (AP) translation, 13.5±12.9 deg in internal-external (IE) rotation, and 5.3±3.4 deg in varus-valgus (VV) rotation; errors were largest in internal-external rotation, and standard deviations reflected differences between teams. While calibrated models were tuned to a similar set of conditions (albeit with different decisions), the optimized stiffness and reference length/strain of ligament structures may not fully reproduce the contributions of these structures to joint kinematics that were measured experimentally in the benchmark scenarios. As researchers often extend models beyond the conditions used to calibrate them, quantifying model accuracy and limitations with benchmarking represents a crucial step toward reproducibility and can help establish best practices for credible modeling in our community.

While computational modeling may help to develop new treatment options for hand and wrist injuries, at present, few models exist. The time and expertise required to develop and use these models is considerable. Moreover, most do not allow for variation of material properties, instead relying on literature reported averages. We have developed a novel automated workflow combining non-linear morphing techniques with various algorithmic techniques to create participant-specific finite element models. Using this workflow, three participant-specific models were created from our existing four-dimensional computed tomography (4DCT) data. These were then used to perform two analyses to demonstrate the usefulness of the models to investigate clinical questions, namely optimization of ligament properties to participant-specific kinematics, and Monte Carlo (MC) analysis of the impacts of ligament injury on joint contact pressure, as an analogue for joint injury that may lead to osteoarthritis. Participant-specific models can be created in 2 hours and individual simulations performed in 45 seconds. This work lays the groundwork for future patient-specific modeling of the hand and wrist.

Despite the documented consequences of modeling decisions on the performance of computational models in orthopaedics and biomechanics, the influence of the input data has largely been ignored. Modeling the living knee is limited by methods to measure in vivo the quantities needed for ligament calibration; yet, this may be possible with new devices focused on non-invasive measurement of knee laxity. These devices offer measurements similar to those commonly obtained from cadaveric specimens but are limited by what can be practically and safely obtained from a living subject. Validation of models calibrated with in vivo data is crucial and increasingly important as personalized modeling becomes the basis for proposed digital twins, and in silico clinical trial workflows. To support our overall goal of building subject-specific models of the living knee, we aimed to show that subject-specific computational models calibrated using in vivo measurements would have accuracy comparable to models calibrated using in vitro measurements. Two cadaveric knee specimens were imaged using a combination of computed tomography (CT) and surface scans. Knee laxity measurements were made with a custom apparatus used for the living knee and from a robotic knee simulator. Models of the knees were built following previous methods and then calibrated with either laxity data from the in vitro robotic knee simulator (RKS) or from the in vivo knee laxity apparatus (KLA). Model performance was compared by simulation of various activities and found to be similar between models calibrated with laxity targets from the RKS and the KLA. Model predictions during simulated anterior-posterior laxity tests differed by less than 2.5 mm and within 2.6° and 2.8 mm during a simulated pivot shift. Still, differences in the predicted ligament loads and calibrated material properties emerged, highlighting a need for methods to include ligament load as part of the calibration process. Overall, the results showed that currently available methods of measuring knee laxity in vivo are sufficient to calibrate models comparable with existing in vitro techniques, and the workflows described here may provide a basis for modeling the living knee. The experimental data, models, results, and tools are publicly available.

Several complications are associated with total shoulder arthroplasty (TSA), including glenoid loosening and joint instability. These complications are linked to imbalances in glenohumeral muscle forces, which cause eccentric loading that occurs on the outer edge of the glenoid component, rather than in the center of the glenoid, and can be damaging to the implant and destabilizing the joint. The purpose of this study was to develop musculoskeletal models of TSA patients using their skeletal geometry acquired from CT and their kinematics acquired with high-speed stereo radiography (HSSR) to predict glenohumeral joint loading and muscle forces for abduction and flexion and describe how these loads differ from their native contralateral side. CT data was collected for both shoulders of 6 TSA patients (three anatomic and three reverse). Models were developed using CT reconstructions of each patient's scapula and humerus, and placed implant geometry with CT-derived alignment. Mesh morphing was used to create personalized muscle attachment sites on the scapula. Simulation of abduction and flexion to quantify muscle and joint forces was driven with limb-specific HSSR kinematics. At 90 deg abduction, reverse TSA increased superior shear force by 11.2% bodyweight (BW) and decreased medial compressive force by 27.5%BW compared to each patient's contralateral shoulder. Lateral deltoid elevation moment arms and stability ratios increased 9.61 mm and 0.58, respectively. At 90 deg abduction, anatomic TSA patients increased humeral internal rotation by 52.7 deg and decreased rotator cuff force by 9.4%BW. Patient-specific musculoskeletal models quantified differences in glenohumeral joint mechanics. This study revealed muscle and kinematic mechanisms that could lead to edge loading and glenoid loosening in TSA and can inform personalized surgical planning for implant alignment with the goal of improving patient outcomes.

Computer representations of three-dimensional (3D) geometries are crucial for simulating systems and processes in engineering and science. In medicine, and more specifically, biomechanics and orthopaedics, obtaining and using 3D geometries is critical to many workflows. However, while many tools exist to obtain 3D geometries of organic structures, little has been done to make them usable for their intended medical purposes. Furthermore, many of the proposed tools are proprietary, limiting their use. This work introduces two novel algorithms based on Generalized Regression Neural Networks (GRNN) and 4 processes to perform mesh morphing and overclosure adjustment. These algorithms were implemented, and test cases were used to validate them against existing algorithms to demonstrate improved performance. The resulting algorithms demonstrate improvements to existing techniques based on Radial Basis Function (RBF) networks by converting to GRNN-based implementations. Implementations in MATLAB of these algorithms and the source code are publicly available at the following locations: https://github.com/thor-andreassen/femors https://simtk.org/projects/femors-rbf https://www.mathworks.com/matlabcentral/fileexchange/120353-finite-element-morphing-overclosure-reduction-and-slicing

Representative data of asymptomatic, native-knee kinematics is important when studying changes in knee function across the lifespan. High-speed stereo radiography (HSSR) provides a reliable measure of knee kine-matics to <1 mm of translation and 1 degrees of rotation, but studies often have limited statistical power to make comparisons between groups or measure the contribution of individual variability. The purpose of this study is to examine in vivo condylar kinematics to quantify the transverse center-of-rotation, or pivot, location across the flexion range and challenge the medial-pivot paradigm in asymptomatic knee kinematics. We quantified the pivot location during supine leg press, knee extension, standing lunge, and gait for 53 middle-aged and older adults (27 men; 26 women: 50.8 +/- 7.0 yrs, 1.75 +/- 0.1 m, 79.1 +/- 15.4 kg). A central-to medial-pivot location was identified for all activities with increased knee flexion associated with posterior translation of the center-of -rotation. The association between knee angle and anterior-posterior center-of-rotation location was not as strong as the relation between medial-lateral and anterior-posterior location, excluding gait. The Pearson's correlation for gait was stronger between knee angle and anterior-posterior center-of-rotation location (P < 0.001) than medial-lateral and anterior-posterior location (P = 0.0122). Individual variability accounted for a measurable proportion in variance explained of center-of-rotation location. Unique to gait, the lateral translation of center -of-rotation location resulted in the anterior translation of center-of-rotation at <10 degrees knee flexion. Furthermore, no association between vertical ground-reaction force and center-of-rotation was identified.

Model reproducibility is a point of emphasis for the National Institutes of Health (NIH) and in science, broadly. As the use of computational modeling in biomechanics and orthopedics grows, so does the need to assess the reproducibility of modeling workflows and simulation predictions. The long-term goal of the KneeHub project is to understand the influence of potentially subjective decisions, thus the modeler's "art", on the reproducibility and predictive uncertainty of computational knee joint models. In this paper, we report on the model calibration phase of this project, during which five teams calibrated computational knee joint models of the same specimens from the same specimen-specific joint mechanics dataset. We investigated model calibration approaches and decisions, and compared calibration workflows and model outcomes among the teams. The selection of the calibration targets used in the calibration workflow differed greatly between the teams and was influenced by modeling decisions related to the representation of structures, and considerations for computational cost and implementation of optimization. While calibration improved model performance, differences in the postcalibration ligament properties and predicted kinematics were quantified and discussed in the context of modeling decisions. Even for teams with demonstrated expertise, model calibration is difficult to foresee and plan in detail, and the results of this study underscore the importance of identification and standardization of best practices for data sharing and calibration.

Models and simulations of human function impact medicine and medical technology. Particularly, musculoskeletal modeling provides an avenue for insight into the human body, which might not be otherwise possible. However, reaching the ultimate goal of functional multi-scale human models has been slowed by the lack of freely available datasets of anatomical models and geometries. Moreover, female-specific geometries have been neglected with a widespread emphasis on male geometry. To help realize this goal, we have developed and shared complete three-dimensional musculoskeletal geometries extracted from the National Libraries of Medicine Visible Human Female and Male cryosections. Muscle, bone, cartilage, ligament, and fat from the pelvis to the ankle were digitized and exported. These geometries provide a foundation for continued work in human musculoskeletal simulation with high-fidelity deformable tissues that enable a better understanding of normal function and the evaluation of pathologies and treatments. This work is novel as it includes both the male and female Visible Human specimens, outputs at multiple levels of post-processing for maximum data reuse, and is publicly available.

A broad generalization in native-knee kinematics is that the transverse axis of internal-external rotation, or pivot, of the tibiofemoral (TF) joint is located on the medial side of the knee. However, mounting evidence suggests that pivot location is not uniform across the flexion range and can vary between functional activities for many while a smaller subset exhibits a uniform pivot pattern. PURPOSE: Quantify knee kinematics and anthropometric differences between native knees that demonstrate uniform pivot location during three activities with varied-pivot controls. METHODS: 54 participants performed a leg press (20 lbs), knee extension, and lunge activity in high-speed stereo radiography to quantify knee kinematics. Grood and Suntay convention was used to calculate the 6-degree of freedom motion about the TF and patellofemoral (PF) joints. Low-point, or nearest-point, kinematics quantified anterior-posterior (AP) translations of the medial and lateral compartments of the femur relative to the tibial plateau. Of the 54, 11 participants (5 men; 51 ± 7 yrs, 26.2 ± 2.9) produced uniform pivot patterns during the three activities and were age-, sex-, and BMI-matched with 11 varied-pivot controls (5 men; 51 ± 7 yrs, 25.6 ± 2.6). RESULTS: The two groups were similar in age, height, weight, and BMI and produced similar ranges of motion in TF kinematics for all three activities. Linear regression revealed differences were greatest in the medial compartment of the TF joint with significantly less AP translation for the uniform-pivot group (leg press = 3 mm [2 4]; knee extension = 4 mm [3 5]; lunge = 2 [1 3]). This group also performed these activities with a significantly shorter patellar tendon (-8.1 mm [-14.1 -2.1]), shorter tibial tuberosity (TT) to patellar AG distance (-7.1 mm [-12.5 -0.5]), lesser Insall-Salvatti ratio (-0.24 [-0.40 -0.1]), and a significantly more valgus patella (leg press = 7.4° [5.8 9.0]; knee extension = 4.1° [2.6 5.7]; lunge = 6.2° [4.0 8.5]). CONCLUSIONS: Participants who demonstrated a uniform TF pivot pattern across multiple activities had significantly smaller TF medial compartment translations, shorter patellar tendon, shorter TT to AG patellar distance, lesser Insall-Salvatti ratio, and a significantly more valgus patella compared with age, sex, and BMI matched varied-pivot controls.

Applying a modified flowerpot technique, which made it possible to use a test animal as its own control, twenty-four hour cycles of locomotor activity were recorded in eight juvenile male rats on 12/12 hr light/dark (LD) schedule during six days of rapid eye movement (REM) sleep deprivation. It was found that the LD difference in locomotor activity unrelated to feeding was instantaneously abolished during REM sleep deprivation. The daily rhythm of food-directed activity, however, was only gradually attenuated. Due to this equalisation in the light and dark activity the rats gave an impression of hyperactivity during the light hours although the total daily motor output after an initial increase returned close to the baseline value.

Secondary femoral fractures after the successful plate-screw fixation of a primary Vancouver type B1 periprosthetic femoral fracture (PFF) have been associated with the altered state of stress/strain in the femur as the result of plating. The laterally implanted condyle-spanning plate-screw constructs have shown promises clinically in avoiding secondary bone and implant failures as compared with shorter diaphyseal plates. Though the condyle-spanning plating has been hypothesized to avoid stress concentration in the femoral diaphysis through increasing the working length of the plate, biomechanical evidence is lacking on how plate length may impact the stress/strain state of the implanted femur. Through developing and experimentally validating finite element (FE) models of 3 cadaveric femurs, this study investigated the impact of plating on bone strains, load transfer and local stiffness, which were compared between FE models of 2 different plating systems that each had a diaphyseal configuration and a condyle-spanning configuration. Under simulated gait-loading, the condyle-spanning constructs of both plating systems were shown to lower the bone strains around the distal fixation screws (up to 24.8% reduction in maximum principal strain and 26.6% reduction in minimum principal strain) and in the distal metaphyseal shaft of the femur (up to 15.9% and 25.7% reductions in maximum and minimum principal strains, respectively), where secondary bone fractures have been typically reported. In the distal diaphyseal and metaphyseal shaft of femur, FE models of the condyle-spanning constructs were shown to increase the local compressive stiffness (up to 152.9% increases under simulated gait-loading) and decrease the transfer of compressive load (37.1% decreases under simulated gait-loading), which may be indicative of the lowered risks of bone damage.

Computational modeling is of growing importance in orthopedics and biomechanics as a tool to understand differences in pathology and predict outcomes from surgical interventions. However, the computational models of the knee have historically relied on in vitro data to create and calibrate model material properties due to the unavailability of accurate in vivo data. This work demonstrates the design and use of a custom device to quantify anterior-posterior (AP) and internal-external (IE) in vivo knee laxity, with an accuracy similar to existing in vitro methods. The device uses high-speed stereo radiography (HSSR) tracking techniques to accurately measure the resulting displacements of the femur, tibia, and patella bones during knee laxity assessment at multiple loads and knee flexion angles. The accuracy of the knee laxity apparatus was determined by comparing laxity data from two cadaveric specimens between the knee laxity apparatus and an existing in vitro robotic knee joint simulator. The accuracy of the knee laxity apparatus was within 1 mm (0.04 in.) for AP and 2.5 deg for IE. Additionally, two living subjects completed knee laxity testing to confirm the laboratory use of the novel apparatus. This work demonstrates the ability to use custom devices in HSSR to collect accurate data, in vivo, for calibration of computational models.