Bayesian Calibration of Computational Knee Models to Estimate Subject-Specific Ligament Properties, Tibiofemoral Kinematics, and Anterior Cruciate Ligament Force With Uncertainty Quantification.

High-grade knee laxity is associated with early anterior cruciate ligament (ACL) graft failure, poor function, and compromised clinical outcome. Yet, the specific ligaments and ligament properties driving knee laxity remain poorly understood. We described a Bayesian calibration methodology for predicting unknown ligament properties in a computational knee model. Then, we applied the method to estimate unknown ligament properties with uncertainty bounds using tibiofemoral kinematics and ACL force measurements from two cadaver knees that spanned a range of laxities; these knees were tested using a robotic manipulator. The unknown ligament properties were from the Bayesian set of plausible ligament properties, as specified by their posterior distribution. Finally, we developed a calibrated predictor of tibiofemoral kinematics and ACL force with their own uncertainty bounds. The calibrated predictor was developed by first collecting the posterior draws of the kinematics and ACL force that are induced by the posterior draws of the ligament properties and model parameters. Bayesian calibration identified unique ligament slack lengths for the two knee models and produced ACL force and kinematic predictions that were closer to the corresponding in vitro measurement than those from a standard optimization technique. This Bayesian framework quantifies uncertainty in both ligament properties and model outputs; an important step towards developing subject-specific computational models to improve treatment for ACL injury.

Subcellular Remodeling in Filamin C Deficient Mouse Hearts Impairs Myocyte Tension Development during Progression of Dilated Cardiomyopathy.

Dilated cardiomyopathy (DCM) is a life-threatening form of heart disease that is typically characterized by progressive thinning of the ventricular walls, chamber dilation, and systolic dysfunction. Multiple mutations in the gene encoding filamin C (FLNC), an actin-binding cytoskeletal protein in cardiomyocytes, have been found in patients with DCM. However, the mechanisms that lead to contractile impairment and DCM in patients with FLNC variants are poorly understood. To determine how FLNC regulates systolic force transmission and DCM remodeling, we used an inducible, cardiac-specific FLNC-knockout (icKO) model to produce a rapid onset of DCM in adult mice. Loss of FLNC reduced systolic force development in single cardiomyocytes and isolated papillary muscles but did not affect twitch kinetics or calcium transients. Electron and immunofluorescence microscopy showed significant defects in Z-disk alignment in icKO mice and altered myofilament lattice geometry. Moreover, a loss of FLNC induces a softening myocyte cortex and structural adaptations at the subcellular level that contribute to disrupted longitudinal force production during contraction. Spatially explicit computational models showed that these structural defects could be explained by a loss of inter-myofibril elastic coupling at the Z-disk. Our work identifies FLNC as a key regulator of the multiscale ultrastructure of cardiomyocytes and therefore plays an important role in maintaining systolic mechanotransmission pathways, the dysfunction of which may be key in driving progressive DCM.

Relationship Between 2-Dimensional Frontal Plane Measures and the Knee Abduction Angle During the Drop Vertical Jump.

Context: Knee abduction angle (KAA), as measured by 3-dimensional marker-based motion capture systems during jump-landing tasks, has been correlated with an elevated risk of anterior cruciate ligament injury in females. Due to the high cost and inefficiency of KAA measurement with marker-based motion capture, surrogate 2-dimensional frontal plane measures have gained attention for injury risk screening. The knee-to-ankle separation ratio (KASR) and medial knee position (MKP) have been suggested as potential frontal plane surrogate measures to the KAA, but investigations into their relationship to the KAA during a bilateral drop vertical jump task are limited. Objective: To investigate the relationship between KASR and MKP to the KAA during initial contact of the bilateral drop vertical jump. Design: Descriptive. Setting: Biomechanics laboratory. Participants: A total of 18 healthy female participants (mean age: 24.1 [3.88] y, mass: 65.18 [10.34] kg, and height: 1.63 [0.06] m). Intervention: Participants completed 5 successful drop vertical jump trials measured by a Vicon marker-based motion capture system and 2 AMTI force plates. Main Outcome Measure: For each jump, KAA of the tibia relative to the femur was measured at initial contact along with the KASR and MKP calculated from planar joint center data. The coefficient of determination (r2) was used to examine the relationship between the KASR and MKP to KAA. Results: A strong linear relationship was observed between MKP and KAA (r2 = .71), as well as between KASR and KAA (r2 = .72). Conclusions: Two-dimensional frontal plane measures show strong relationships to the KAA during the bilateral drop vertical jump.

Electromyography-Driven Forward Dynamics Simulation to Estimate In Vivo Joint Contact Forces During Normal, Smooth, and Bouncy Gaits.

Computational models that predict in vivo joint loading and muscle forces can potentially enhance and augment our knowledge of both typical and pathological gaits. To adopt such models into clinical applications, studies validating modeling predictions are essential. This study created a full-body musculoskeletal model using data from the "Sixth Grand Challenge Competition to Predict in vivo Knee Loads." This model incorporates subject-specific geometries of the right leg in order to concurrently predict knee contact forces, ligament forces, muscle forces, and ground contact forces. The objectives of this paper are twofold: (1) to describe an electromyography (EMG)-driven modeling methodology to predict knee contact forces and (2) to validate model predictions by evaluating the model predictions against known values for a patient with an instrumented total knee replacement (TKR) for three distinctly different gait styles (normal, smooth, and bouncy gaits). The model integrates a subject-specific knee model onto a previously validated generic full-body musculoskeletal model. The combined model included six degrees-of-freedom (6DOF) patellofemoral and tibiofemoral joints, ligament forces, and deformable contact forces with viscous damping. The foot/shoe/floor interactions were modeled by incorporating shoe geometries to the feet. Contact between shoe segments and the floor surface was used to constrain the shoe segments. A novel EMG-driven feedforward with feedback trim motor control strategy was used to concurrently estimate muscle forces and knee contact forces from standard motion capture data collected on the individual subject. The predicted medial, lateral, and total tibiofemoral forces represented the overall measured magnitude and temporal patterns with good root-mean-squared errors (RMSEs) and Pearson's correlation (p2). The model accuracy was high: medial, lateral, and total tibiofemoral contact force RMSEs = 0.15, 0.14, 0.21 body weight (BW), and (0.92 < p2 < 0.96) for normal gait; RMSEs = 0.18 BW, 0.21 BW, 0.29 BW, and (0.81 < p2 < 0.93) for smooth gait; and RMSEs = 0.21 BW, 0.22 BW, 0.33 BW, and (0.86 < p2 < 0.95) for bouncy gait, respectively. Overall, the model captured the general shape, magnitude, and temporal patterns of the contact force profiles accurately. Potential applications of this proposed model include predictive biomechanics simulations, design of TKR components, soft tissue balancing, and surgical simulation.

Comparison of 3D Joint Angles Measured With the Kinect 2.0 Skeletal Tracker Versus a Marker-Based Motion Capture System.

The Microsoft Kinect is becoming a widely used tool for inexpensive, portable measurement of human motion, with the potential to support clinical assessments of performance and function. In this study, the relative osteokinematic Cardan joint angles of the hip and knee were calculated using the Kinect 2.0 skeletal tracker. The pelvis segments of the default skeletal model were reoriented and 3-dimensional joint angles were compared with a marker-based system during a drop vertical jump and a hip abduction motion. Good agreement between the Kinect and marker-based system were found for knee (correlation coefficient = 0.96, cycle RMS error = 11°, peak flexion difference = 3°) and hip (correlation coefficient = 0.97, cycle RMS = 12°, peak flexion difference = 12°) flexion during the landing phase of the drop vertical jump and for hip abduction/adduction (correlation coefficient = 0.99, cycle RMS error = 7°, peak flexion difference = 8°) during isolated hip motion. Nonsagittal hip and knee angles did not correlate well for the drop vertical jump. When limited to activities in the optimal capture volume and with simple modifications to the skeletal model, the Kinect 2.0 skeletal tracker can provide limited 3-dimensional kinematic information of the lower limbs that may be useful for functional movement assessment.

Multi-organ transcriptome atlas of a mouse model of relative energy deficiency in sport.

Insufficient energy intake to meet energy expenditure demands of physical activity can result in systemic neuroendocrine and metabolic abnormalities in activity-dependent anorexia and relative energy deficiency in sport (REDs). REDs affects >40% of athletes, yet the lack of underlying molecular changes has been a hurdle to have a better understanding of REDs and its treatment. To assess the molecular changes in response to energy deficiency, we implemented the "exercise-for-food" paradigm, in which food reward size is determined by wheel-running activity. By using this paradigm, we replicated several aspects of REDs in female and male mice with high physical activity and gradually reduced food intake, which results in weight loss, compromised bone health, organ-specific mass changes, and altered rest-activity patterns. By integrating transcriptomics of 19 different organs, we provide a comprehensive dataset that will guide future understanding of REDs and may provide important implications for metabolic health and (athletic) performance.

Prediction of patellofemoral joint kinematics and contact through co-simulation of rigid body dynamics and nonlinear finite element analysis.

Joint-level rigid body dynamics simulations, when coupled with tissue-level finite element analyses, can simultaneously provide movement and tissue deformation metrics to understand mechanical interactions within the joint on a multi-scale level. In this study, a co-simulation workflow of a joint-level rigid body model that predicts the relative motion as a function of the non-linear cartilage response predicted by a non-linear implicit finite element solver is presented. Predictions are compared to in-vitro measurements (The Open Knee(s) project) in terms of the mean error and level-of-agreement: pressureerror = 0.46 MPa (level-of-agreement, -0.23 - 1.1 MPa); areaerror = -89 mm2 (level-of-agreement, -280 - 98 mm2) and contact forceerror = 93 N (level-of-agreement, 7.8 - 180 N). The automated co-simulation control algorithm enables multiscale coupling between joint and tissue-level models with real-time two-way communication as opposed to the traditional feed-forward approach of multi-scale models.

Femoral Component Malrotation Produces Quadriceps Weakness and Impaired Ambulatory Function following Total Knee Arthroplasty: Results of a Forward-Dynamic Computer Model.

Proper placement of the prosthetic components is believed to be an important factor in successful total knee arthroplasty (TKA). Implant positioning errors have been associated with postoperative pain, suboptimal function, and inferior patient-reported outcome measures. The purpose of this study was to investigate the biomechanical effects of femoral component malrotation on quadriceps function and normal ambulation. For the investigation, publicly available data were used to create a validated forward-dynamic, patient-specific computer model. The incorporated data included medical imaging, gait laboratory measurements, knee loading information, electromyographic data, strength testing, and information from the surgical procedure. The ideal femoral component rotation was set to the surgical transepicondylar axis and walking simulations were subsequently performed with increasing degrees of internal and external rotation of the femoral component. The muscle force outputs were then recorded for the quadriceps musculature as a whole, as well as for the individual constituent muscles. The quadriceps work requirements during walking were then calculated for the different rotational simulations. The highest forces generated by the quadriceps were seen during single-limb stance phase as increasing degrees of femoral internal rotation produced proportional increases in quadriceps force requirements. The individual muscles of the quadriceps displayed different sensitivities to the rotational variations introduced into the simulations with the vastus lateralis showing the greatest changes with rotational positioning. Increasing degrees of internal rotation of femoral component were also seen to demand increasing quadriceps work to support normal ambulation. In conclusion, internal malrotation of the femoral component during TKA produces a mechanically disadvantaged state which is characterized by greater required quadriceps forces (especially the vastus lateralis) and greater quadriceps work to support normal ambulation.

Function of the Anterior Intermeniscal Ligament.

The function and importance of the anterior intermeniscal ligament (AIML) of the knee are not fully known. The purpose of this study was to evaluate the biomechanical and sensorimotor function of the AIML. Computational analysis was used to assess AIML and tibiomeniscofemoral biomechanics under combined translational and rotational loading applied during dynamic knee flexion-extension. Histologic and immunohistochemical examination was used to identify and characterize neural elements in the tissue. The computational models were created from anatomy and passive motion of two female subjects and histologic examinations were conducted on AIMLs retrieved from 10 fresh-frozen cadaveric knees. It was found that AIML strain increased with compressive knee loading and that external rotation of the tibia unloads the AIML, suppressing the relationship between AIML strain and compressive knee loads. Extensive neural elements were located throughout the AIML tissue and these elements were distributed across the three AIML anatomical types. The AIMLs have a beneficial influence on knee biomechanics with decreased meniscal load sharing with AIML loss. The AIML plays a significant biomechanical and neurologic role in the sensorimotor functions of the knee. The major role for the AIML may primarily involve its neurologic function.

Loading of the medial meniscus in the ACL deficient knee: A multibody computational study.

The menisci of the knee reduce tibiofemoral contact pressures and aid in knee lubrication and nourishment. Meniscal injury occurs in half of knees sustaining anterior cruciate ligament injury and the vast majority of tears in the medial meniscus transpire in the posterior horn region. In this study, computational multibody models of the knee were derived from medical images and passive leg motion for two female subjects. The models were validated against experimental measures available in the literature and then used to evaluate medial meniscus contact force and internal hoop tension. The models predicted that the loss of anterior cruciate ligament (ACL) constraint increased contact and hoop forces in the medial menisci by a factor of 4 when a 100N anterior tibial force was applied. Contact forces were concentrated in the posterior horn and hoop forces were also greater in this region. No differences were found in contact or hoop tension between the intact and ACL deficient (ACLd) knees when only a 5Nm external tibial torque was applied about the long axis of the tibia. Combining a 100N anterior tibial force and a 5Nm external tibial torque increased posterior horn contact and hoop forces, even in the intact knee. The results of this study show that the posterior horn region of the medial meniscus experiences higher contact forces and hoop tension, making this region more susceptible to injury, especially with the loss of anterior tibia motion constraint provided by the ACL. The contribution of the dMCL in constraining posterior medial meniscus motion, at the cost of higher posterior horn hoop tension, is also demonstrated.

Development and Validation of a Portable and Inexpensive Tool to Measure the Drop Vertical Jump Using the Microsoft Kinect V2.

BACKGROUND: Noncontact anterior cruciate ligament (ACL) injury in adolescent female athletes is an increasing problem. The knee-ankle separation ratio (KASR), calculated at initial contact (IC) and peak flexion (PF) during the drop vertical jump (DVJ), is a measure of dynamic knee valgus. The Microsoft Kinect V2 has shown promise as a reliable and valid marker-less motion capture device. HYPOTHESIS: The Kinect V2 will demonstrate good to excellent correlation between KASR results at IC and PF during the DVJ, as compared with a "gold standard" Vicon motion analysis system. STUDY DESIGN: Descriptive laboratory study. LEVEL OF EVIDENCE: Level 2. METHODS: Thirty-eight healthy volunteer subjects (20 male, 18 female) performed 5 DVJ trials, simultaneously measured by a Vicon MX-T40S system, 2 AMTI force platforms, and a Kinect V2 with customized software. A total of 190 jumps were completed. The KASR was calculated at IC and PF during the DVJ. The intraclass correlation coefficient (ICC) assessed the degree of KASR agreement between the Kinect and Vicon systems. RESULTS: The ICCs of the Kinect V2 and Vicon KASR at IC and PF were 0.84 and 0.95, respectively, showing excellent agreement between the 2 measures. The Kinect V2 successfully identified the KASR at PF and IC frames in 182 of 190 trials, demonstrating 95.8% reliability. CONCLUSION: The Kinect V2 demonstrated excellent ICC of the KASR at IC and PF during the DVJ when compared with the Vicon system. A customized Kinect V2 software program demonstrated good reliability in identifying the KASR at IC and PF during the DVJ. CLINICAL RELEVANCE: Reliable, valid, inexpensive, and efficient screening tools may improve the accessibility of motion analysis assessment of adolescent female athletes.

Evaluation of Knee Ligament Mechanics Using Computational Models.

The steady maturation of computational biomechanics is providing the musculoskeletal health community with exciting avenues for enhancing orthopedic practice and rehabilitation. Computational knee models deliver tools that may improve the efficiency and outcomes of orthopedic research and methods through analysis of virtual surgeries and devices. They also provide insight into the interaction of knee structures and can predict what cannot be directly measured such as loading on our cartilage and ligaments during movement. This project created subject-specific computational knee models of two young adult females using magnetic resonance imaging-derived knee geometries and passive leg motion measured by a motion capture system. The knee models produced passive ligament lengthening patterns similar to experimental measurements available in the literature. The models also predicted cruciate ligament forces during passive flexion with and without applying anterior-posterior tibia forces that were similar to experimental measurements available in the literature. The biomechanics of the posterior oblique ligament (POL) and the anterior cruciate ligament bundles during combined tibia internal-external rotation torque and anterior-posterior forces through deep flexion were then examined. The study showed that the central arm of the POL: (1) produces a maximum constraining force when the knee is at full extension, (2) constrains internal tibial rotation at extension, and (3) constrains posterior tibial translation at extension. The POL reinforces the constraint of the anterior cruciate ligament to internal rotation at extension and provides constraint for posterior tibial translation at extension, a position where the posterior cruciate ligament provides minimal posterior translation constraint.

Predicted loading on the menisci during gait: The effect of horn laxity.

Radiographic measurements have established a link between meniscus extrusion and meniscus degeneration as well as with knee osteoarthritis. The presented work combines medical imaging with motion capture data from two healthy female subjects to create subject specific knee models that predict tibio-menisco-femoral contact forces and ligament forces during muscle driven simulations of barefoot gait. The developed computational models were used to explore the relationship between the extent of meniscal extrusion and biomechanical function by altering the laxity of the meniscal horn attachments during gait. The extrusion distance increased as laxity increased and the amount of contact force transferred through the menisci during gait decreased rapidly as the meniscal attachments became more lax. Horn attachment lengths that were 20% longer than MRI attachment lengths resulted in an almost complete loss of force transfer through the menisci during the gait cycle. Relatively small changes (2-3mm) in the lengths at which horn bundles first become taut, manifested in large changes in the capacity of the tissue to transmit forces. As meniscal horn attachment laxity increased from 80% to 120% of the MRI measured horn distance, medial meniscus extrusion increased 3.9mm for the first subject and 2.7mm for the second subject. For the same horn laxity changes, the percent of medial tibiofemoral contact force transmitted through the medial meniscus during early stance decreased from 51% to 8% and from 36% to 14% for the two subjects. The results of our study show that increased meniscal extrusion occurs with increased laxity of the meniscal tibia attachments and this increased laxity results in loss of meniscal function.