Development and validation of a subject-specific moving-axis tibiofemoral joint model using MRI and EOS imaging during a quasi-static lunge

The aims of this study were to introduce and validate a novel computationally-efficient subject-specific tibiofemoral joint model. Subjects performed a quasi-static lunge while micro-dose radiation bi-planar X-rays (EOS Imaging, Paris, France) were captured at roughly 0°, 20°, 45°, 60°, and 90° of tibiofemoral flexion. Joint translations and rotations were extracted from this experimental data through 2D-to-3D bone reconstructions, using an iterative closest point optimization technique, and employed during model calibration and validation. Subject-specific moving-axis and hinge models for comparisons were constructed in the AnyBody Modeling System (AMS) from Magnetic Resonance Imaging (MRI)-extracted anatomical surfaces and compared against the experimental data. The tibiofemoral axis of the hinge model was defined between the epicondyles while the moving-axis model was defined based on two tibiofemoral flexion angles (0° and 90°) and the articulation modeled such that the tibiofemoral joint axis moved linearly between these two positions as a function of the tibiofemoral flexion. Outside this range, the joint axis was assumed to remain stationary. Overall, the secondary joint kinematics (ML: medial–lateral, AP: anterior-posterior, SI: superior-inferior, IE: internal-external, AA: adduction-abduction) were better approximated by the moving-axis model with mean differences and standard errors of (ML: −1.98 ± 0.37 mm, AP: 6.50 ± 0.82 mm, SI: 0.05 ± 0.20 mm, IE: 0.59 ± 0.36°, AA: 1.90 ± 0.79°) and higher coefficients of determination (R²) for each clinical measure. While the hinge model achieved mean differences and standard errors of (ML: −0.84 ± 0.45 mm, AP: 10.11 ± 0.88 mm, SI: 0.66 ± 0.62 mm, IE: −3.17 ± 0.86°, AA: 11.60 ± 1.51°).     

Development and validation of a computational model of the knee joint for the evaluation of surgical treatments for osteoarthritis

A three-dimensional (3D) knee joint computational model was developed and validated to predict knee joint contact forces and pressures for different degrees of malalignment. A 3D computational knee model was created from high-resolution radiological images to emulate passive sagittal rotation (full-extension to 65°-flexion) and weight acceptance. A cadaveric knee mounted on a six-degree-of-freedom robot was subjected to matching boundary and loading conditions. A ligament-tuning process minimised kinematic differences between the robotically loaded cadaver specimen and the finite element (FE) model. The model was validated by measured intra-articular force and pressure measurements. Percent full scale error between FE-predicted and in vitro-measured values in the medial and lateral compartments were 6.67% and 5.94%, respectively, for normalised peak pressure values, and 7.56% and 4.48%, respectively, for normalised force values. The knee model can accurately predict normalised intra-articular pressure and forces for different loading conditions and could be further developed for subject-specific surgical planning.     

An improved OpenSim gait model with multiple degrees of freedom knee joint and knee ligaments

Musculoskeletal models are widely used to investigate joint kinematics and predict muscle force during gait. However, the knee is usually simplified as a one degree of freedom joint and knee ligaments are neglected. The aim of this study was to develop an OpenSim gait model with enhanced knee structures. The knee joint in this study included three rotations and three translations. The three knee rotations and mediolateral translation were independent, with proximodistal and anteroposterior translations occurring as a function of knee flexion/extension. Ten elastic elements described the geometrical and mechanical properties of the anterior and posterior cruciate ligaments (ACL and PCL), and the medial and lateral collateral ligaments (MCL and LCL). The three independent knee rotations were evaluated using OpenSim to observe ligament function. The results showed that the anterior and posterior bundles of ACL and PCL (aACL, pACL and aPCL, pPCL) intersected during knee flexion. The aACL and pACL mainly provided force during knee flexion and adduction, respectively. The aPCL was slack throughout the range of three knee rotations; however, the pPCL was utilised for knee abduction and internal rotation. The LCL was employed for knee adduction and rotation, but was slack beyond 20° of knee flexion. The MCL bundles were mainly used during knee adduction and external rotation. All these results suggest that the functions of knee ligaments in this model approximated the behaviour of the physical knee and the enhanced knee structures can improve the ability to investigate knee joint biomechanics during various gait activities.     

Distribution of lactate dehydrogenase in healthy and degenerative canine stifle joint cartilage

In dogs, degenerative joint diseases (DJD) have been shown to be associated with increased lactate dehydrogenase (LDH) activity in the synovial fluid. The goal of this study was to examine healthy and degenerative stifle joints in order to clarify the origin of LDH in synovial fluid. In order to assess the distribution of LDH, cartilage samples from healthy and degenerative knee joints were investigated by means of light and transmission electron microscopy in conjunction with immunolabeling and enzyme cytochemistry. Morphological analysis confirmed DJD. All techniques used corroborated the presence of LDH in chondrocytes and in the interterritorial matrix of healthy and degenerative stifle joints. Although enzymatic activity of LDH was clearly demonstrated in the territorial matrix by means of the tetrazolium–formazan reaction, immunolabeling for LDH was missing in this region. With respect to the distribution of LDH in the interterritorial matrix, a striking decrease from superficial to deeper layers was present in healthy dogs but was missing in affected joints. These results support the contention that LDH in synovial fluid of degenerative joints originates from cartilage. Therefore, we suggest that (1) LDH is transferred from chondrocytes to ECM in both healthy dogs and dogs with degenerative joint disease and that (2) in degenerative joints, LDH is released from chondrocytes and the ECM into synovial fluid through abrasion of cartilage as well as through enhanced diffusion as a result of increased water content and degradation of collagen.     

Development and validation of a weight-bearing finite element model for total knee replacement

Total knee arthroplasty (TKA) is a successful procedure for osteoarthritis. However, some patients (19%) do have pain after surgery. A finite element model was developed based on boundary conditions of a knee rig. A 3D-model of an anatomical full leg was generated from magnetic resonance image data and a total knee prosthesis was implanted without patella resurfacing. In the finite element model, a restarting procedure was programmed in order to hold the ground reaction force constant with an adapted quadriceps muscle force during a squat from 20° to 105° of flexion. Knee rig experimental data were used to validate the numerical model in the patellofemoral and femorotibial joint. Furthermore, sensitivity analyses of Young’s modulus of the patella cartilage, posterior cruciate ligament (PCL) stiffness, and patella tendon origin were performed. Pearson’s correlations for retropatellar contact area, pressure, patella flexion, and femorotibial ap-movement were near to 1. Lowest root mean square error for retropatellar pressure, patella flexion, and femorotibial ap-movement were found for the baseline model setup with Young’s modulus of 5 MPa for patella cartilage, a downscaled PCL stiffness of 25% compared to the literature given value and an anatomical origin of the patella tendon. The results of the conducted finite element model are comparable with the experimental results. Therefore, the finite element model developed in this study can be used for further clinical investigations and will help to better understand the clinical aspects after TKA with an unresurfaced patella.     

A multi-body dynamics study on a weight-drop test of rat brain injury

Traumatic brain injury (TBI), induced by impact of an object with the head, is a major health problem worldwide. Rats are a well-established animal analogue for study of TBI and the weight-drop impact-acceleration (WDIA) method is a well-established model in rats for creating diffuse TBI, the most common form of TBI seen in humans. However, little is known of the biomechanics of the WDIA method and, to address this, we have developed a four-degrees-of-freedom multi-body mass-spring-damper model for the WDIA test in rats. An analytical expression of the maximum skull acceleration, one of the important head injury predictor, was derived and it shows that the maximum skull acceleration is proportional to the impact velocity but independent of the impactor mass. Furthermore, a dimensional analysis disclosed that the maximum force on the brain and maximum relative displacement between brain and skull are also linearly proportional to impact velocity. Additionally, the effects of the impactor mass were examined through a parametric study from the developed multi-body dynamics model. It was found that increasing impactor mass increased these two brain injury predictors.     

Articular cartilage in the knee joint of the African elephant, Loxodonta africana, Blumenbach 1797

Knee joints of one adult and three juvenile African elephants were dissected. The specific features of the articular cartilage with particular reference to matrix components were studied by light and electron microscopy and immunohistochemistry. The elephant knee joint cartilage contains an unusually low concentration of proteoglycans resulting in rather eosinophilic staining properties of the matrix. The very thick collagen fibers of the cartilage possibly represent collagen I. Except for the different thickness of cartilage at the weight-bearing surfaces of femur (approximately 6.7 mm) and tibia (approximately 11.2 mm) in juvenile elephants, light and electron microscopy did not reveal distinct topographical differences in cartilage structure, perhaps because of the high congruency of the articulating surfaces and resulting uniform load distribution in the knee. The number of cell profiles per section area of both femoral (approximately 950 cell profiles/mm(2)) and tibial cartilage (approximately 898 cell profiles/mm(2)) was low, indicating excessive matrix production by the chondrocytes during cartilage development. These unique properties could be a result of the enormous compressive load resting on the elephant knee. Maintenance of the equilibrium between biological function and resistance to compression seems to be crucial in the elephant knee joint cartilage. Any disturbance that interferes with this equilibrium appears to lead to arthrotic alterations, as particularly seen in captive elephants.     

Development and validation of a kinematically-driven discrete element model of the patellofemoral joint

Quantifying the complex loads at the patellofemoral joint (PFJ) is vital to understanding the development of PFJ pain and osteoarthritis. Discrete element analysis (DEA) is a computationally efficient method to estimate cartilage contact stresses with potential application at the PFJ to better understand PFJ mechanics. The current study validated a DEA modeling framework driven by PFJ kinematics to predict experimentally-measured PFJ contact stress distributions. Two cadaveric knee specimens underwent quadriceps muscle [215 N] and joint compression [350 N] forces at ten discrete knee positions representing PFJ positions during early gait while measured PFJ kinematics were used to drive specimen-specific DEA models. DEA-computed contact stress and area were compared to experimentally-measured data. There was good agreement between computed and measured mean and peak stress across the specimens and positions (r = 0.63–0.85). DEA-computed mean stress was within an average of 12% (range: 1–47%) of the experimentally-measured mean stress while DEA-computed peak stress was within an average of 22% (range: 1–40%). Stress magnitudes were within the ranges measured (0.17–1.26 MPa computationally vs 0.12–1.13 MPa experimentally). DEA-computed areas overestimated measured areas (average error = 60%; range: 4–117%) with magnitudes ranging from 139 to 307 mm² computationally vs 74–194 mm² experimentally. DEA estimates of the ratio of lateral to medial patellofemoral stress distribution predicted the experimental data well (mean error = 15%) with minimal measurement bias. These results indicate that kinematically-driven DEA models can provide good estimates of relative changes in PFJ contact stress.     

Development of a statistical shape-function model of the implanted knee for real-time prediction of joint mechanics

Outcomes of total knee arthroplasty (TKA) are dependent on surgical technique, patient variability, and implant design. Non-optimal design or alignment choices may result in undesirable contact mechanics and joint kinematics, including poor joint alignment, instability, and reduced range of motion. Implant design and surgical alignment are modifiable factors with potential to improve patient outcomes, and there is a need for robust implant designs that can accommodate patient variability. Our objective was to develop a statistical shape-function model (SFM) of a posterior stabilized implanted knee to instantaneously predict joint mechanics in an efficient manner. Finite element methods were combined with Latin hypercube sampling and regression analyses to produce modeling equations relating nine implant design and six surgical alignment parameters to tibiofemoral (TF) joint mechanics outcomes during a deep knee bend. A SFM was developed and TF contact mechanics, kinematics, and soft tissue loads were instantaneously predicted from the model. Average normalized root-mean-square error predictions were between 2.79% and 9.42%, depending on the number of parameters included in the model. The statistical shape-function model generated instantaneous joint mechanics predictions using a maximum of 130 training simulations, making it ideally suited for integration into a patient-specific design and alignment optimization pipeline. Such a tool may be used to optimize kinematic function to achieve more natural motion or minimize implant wear, and may aid the engineering and clinical communities in improving patient satisfaction and surgical outcomes.     

Safety and immunomodulatory effects of allogeneic canine adipose-derived mesenchymal stromal cells transplanted into the region of the lacrimal gland,the gland of the third eyelid and the knee joint

Background aimsMesenchymal stromal cells (MSCs) have been extensively studied as a cellular therapeutic for various pathologic conditions. However, there remains a paucity of data regarding regional and systemic safety of MSC transplantations, particularly with multiple deliveries of allogeneic cells. The purpose of this study was to investigate the safety and systemic immunomodulatory effects of repeated local delivery of allogeneic MSCs into the region of the lacrimal gland, the gland of the third eyelid and the knee joint in dogs.MethodsAllogeneic adipose tissue-derived canine MSCs were delivered to the regions of the lacrimal gland and the third eyelid gland as well as in the knee joints of six healthy laboratory beagles as follows: six times with 1-week intervals for delivery to the lacrimal gland and the third eyelid gland regions and three to four times with 1- to 2-week intervals for intra-articular transplantations. Dogs were sequentially evaluated by clinical examination. At the conclusion of the study, dogs were humanely euthanized, and a complete gross and histopathologic examination of all organ systems was performed. Mixed leukocyte reactions were also performed before the first transplantation and after the final transplantation.ResultsClinical and pathologic examinations found no severe consequences after repeated MSC transplantations. Results of mixed leukocyte reactions demonstrated suppression of T-cell proliferation after MSC transplantations.ConclusionsThis is the first study to demonstrate regional and systemic safety and systemic immunomodulatory effects of repeated local delivery of allogeneic MSCs in vivo.     

Development and validation of a generic 3D model of the distal femur

The development and validation of a virtual generic 3D model of the distal femur using computer graphical methods is presented. The synthesis of the generic model requires the following steps: acquisition of bony 3D morphology using standard computed tomography (CT) imaging; alignment of 3D models reconstructed from CT images with a common coordinate system; computer graphical sectioning of the models; extraction of bone contours from the image sections; combining and averaging of extracted contours; and 3D reconstruction of the averaged contours.

The generic models reconstructed from the averaged contours of six cadaver femora were validated by comparing their surface geometry on a point to point basis with that of the CT reconstructed reference models. The mean errors ranged from 0.99 to 2.5 mm and were in agreement with the qualitative assessment of the models.     

Development of a finite element/multi-body model of a newborn infant for restraint analysis and design

A finite element/multi-body model of a newborn infant has been developed by researchers at the University of Windsor. The geometry of this model is derived from a Nita newborn hospital training mannequin. It consists of 17 parts: eight upper and lower limb segments, the torso, head, and a seven-segment neck with seven translational and eight rotational joints. Anthropometry is consistent with hospital growth charts, measurements requested from health professionals and data from the open literature. The biomechanical properties of the model (i.e. joint stiffnesses) are implementations of data identified in the open literature. The model has been validated with respect to studies of the biomechanics of shaken baby syndrome, infant falls and the Q0 anthropomorphic testing device. A significant conclusion of this study is that the kinetics of the Q0 neck is not biofidelic. This model is currently used in an analysis of airway patency for infants in modern automotive child restraints.     

Development and validation of a simulation model for blowfly strike of sheep

A comprehensive simulation model for sheep blowfly strike due to Lucilia sericata (Meigen) (Diptera: Calliphoridae), which builds on previously published versions but also incorporates important new empirical data, is used to explain patterns of lamb and ewe strike recorded on 370 farms in south-west, south-east and central England and Wales. The model is able to explain a significant percentage of the variance in lamb strike incidence in all four regions, and ewe strike in three of the four regions. The model is able to predict the start of seasonal blowfly strike within one week in three of the four regions for both ewes and lambs, and within 3 weeks in the fourth region. It is concluded that the accuracy of the model will allow it to be used to assess the likely efficacy of new control techniques and the effects of changes in existing husbandry practices on strike incidence. The model could also be used to give sheep farmers advance warning of approaching strike problems. However, the ability to forecast future strike patterns is dependent on the accuracy of the weather projections; the more long-term the forecast, the more approximate the prediction is likely to be. When applied on a regional basis, model forecasts indicate expected average patterns of strike incidence and may not therefore be appropriate for individual farmers whose husbandry practices differ substantially from the average.     

Development and validation of a 3-D model to predict knee joint loading during dynamic movement

The purpose of this study was to develop a subject-specific 3-D model of the lower extremity to predict neuromuscular control effects on 3-D knee joint loading during movements that can potentially cause injury to the anterior cruciate ligament (ACL) in the knee. The simulation consisted of a forward dynamic 3-D musculoskeletal model of the lower extremity, scaled to represent a specific subject. Inputs of the model were the initial position and velocity of the skeletal elements, and the muscle stimulation patterns. Outputs of the model were movement and ground reaction forces, as well as resultant 3-D forces and moments acting across the knee joint. An optimization method was established to find muscle stimulation patterns that best reproduced the subject's movement and ground reaction forces during a sidestepping task. The optimized model produced movements and forces that were generally within one standard deviation of the measured subject data. Resultant knee joint loading variables extracted from the optimized model were comparable to those reported in the literature. The ability of the model to successfully predict the subject's response to altered initial conditions was quantified and found acceptable for use of the model to investigate the effect of altered neuromuscular control on knee joint loading during sidestepping. Monte Carlo simulations (N = 100,000) using randomly perturbed initial kinematic conditions, based on the subject's variability, resulted in peak anterior force, valgus torque and internal torque values of 378 N, 94 Nm and 71 Nm, respectively, large enough to cause ACL rupture. We conclude that the procedures described in this paper were successful in creating valid simulations of normal movement, and in simulating injuries that are caused by perturbed neuromuscular control.     

Isolation and characterization of microsatellites from the canine genome

Microsatellite sequences comprising (dC-dA)_n.(dG-dT)_n repeats have been isolated from canine libraries and sequenced. Oligonucleotide primers have been synthesized to the micro-satellite flanking sequences and used in the polymerase chain reaction to amplify those loci from genomic DNA. The degree of polymorphism of each microsatellite was estimated in a set of unrelated dogs. It is concluded that of the 10 loci studied, nine are sufficiently polymorphic to be useful in genetic studies.     

Multiple imputation for discrete data: Evaluation of the joint latent normal model

Missing data are ubiquitous in clinical and social research, and multiple imputation (MI) is increasingly the methodology of choice for practitioners. Two principal strategies for imputation have been proposed in the literature: joint modelling multiple imputation (JM‐MI) and full conditional specification multiple imputation (FCS‐MI). While JM‐MI is arguably a preferable approach, because it involves specification of an explicit imputation model, FCS‐MI is pragmatically appealing, because of its flexibility in handling different types of variables. JM‐MI has developed from the multivariate normal model, and latent normal variables have been proposed as a natural way to extend this model to handle categorical variables. In this article, we evaluate the latent normal model through an extensive simulation study and an application on data from the German Breast Cancer Study Group, comparing the results with FCS‐MI. We divide our investigation in four sections, focusing on (i) binary, (ii) categorical, (iii) ordinal, and (iv) count data. Using data simulated from both the latent normal model and the general location model, we find that in all but one extreme general location model setting JM‐MI works very well, and sometimes outperforms FCS‐MI. We conclude the latent normal model, implemented in the R package jomo , can be used with confidence by researchers, both for single and multilevel multiple imputation.