Sensitivity of tibio-menisco-femoral joint contact behavior to variations in knee kinematics

Use of computational models with kinematic boundary conditions to study the knee joint contact behavior for normal and pathologic knee joints depends on an understanding of the impacts of kinematic uncertainty. We studied the sensitivities of tibio-menisco-femoral joint contact behavior to variations in knee kinematics using a finite element model (FEM) with geometry and kinematic boundary conditions derived from sequences of magnetic resonance (MR) images. The MR images were taken before and after axial compression was applied to the knee joint of a healthy subject. A design of experiments approach was used to study the impact of the variation in knee kinematics on the contact outputs. We also explored the feasibility of using supplementary hip images to improve the accuracy of knee kinematics. Variations in knee kinematics (0.25mm in medial-lateral, 0.1mm in anterior-posterior and superior-inferior translations, and 0.1 degrees in flexion-extension and varus-valgus, 0.25 degrees in external-internal rotations) caused large variations in joint contact behavior. When kinematic boundary conditions resulted in close approximations of the model-predicted joint contact force to the applied force, variations in predictions of contact parameters were also reduced. The combination of inferior-superior and medial-lateral translations accounted for over 70% of variations for all the contact parameters examined. The inclusion of hip images in kinematic calculations improved knee kinematics by matching the femoral head position. Our findings demonstrate the importance of improving the accuracy and precision of knee kinematic measurements, especially when utilized as an input for finite element models.     

The use of sequential MR image sets for determining tibiofemoral motion: reliability of coordinate systems and accuracy of motion tracking algorithm

The use of magnetic resonance imaging has been proposed by many investigators for establishment of joint reference systems and kinematic tracking of musculoskeletal joints. In this study, the intraobserver and interobserver reliability of a strategy to establish anatomic reference systems using manually selected fiducial points were quantified for seven sets of MR images of the human knee joint. The standard error of the measurement of the intraobserver and interobserver errors were less than 2.6 degrees, and 1.2 mm for relative tibiofemoral orientation and displacement, respectively. An automated motion tracking algorithm was also validated with a controlled motion experiment in a cadaveric knee joint. The controlled displacements and rotations prescribed in our motion tracking validation were highly correlated to those predicted (Pearson's correlation = 0.99, RMS errors = 0.39 mm, 0.38 degree). Finally, the system for anatomic reference system definition and motion tracking was demonstrated with a set of MR images of in vivo passive flexion in the human knee.     

Measurement of in vivo anterior cruciate ligament strain during dynamic jump landing

Despite recent attention in the literature, anterior cruciate ligament (ACL) injury mechanisms are controversial and incidence rates remain high. One explanation is limited data on in vivo ACL strain during high-risk, dynamic movements. The objective of this study was to quantify ACL strain during jump landing. Marker-based motion analysis techniques were integrated with fluoroscopic and magnetic resonance (MR) imaging techniques to measure dynamic ACL strain non-invasively. First, eight subjects' knees were imaged using MR. From these images, the cortical bone and ACL attachment sites of the tibia and femur were outlined to create 3D models. Subjects underwent motion analysis while jump landing using reflective markers placed directly on the skin around the knee. Next, biplanar fluoroscopic images were taken with the markers in place so that the relative positions of each marker to the underlying bone could be quantified. Numerical optimization allowed jumping kinematics to be superimposed on the knee model, thus reproducing the dynamic in vivo joint motion. ACL length, knee flexion, and ground reaction force were measured. During jump landing, average ACL strain peaked 55±14 ms (mean and 95% confidence interval) prior to ground impact, when knee flexion angles were lowest. The peak ACL strain, measured relative to its length during MR imaging, was 12±7%. The observed trends were consistent with previously described neuromuscular patterns. Unrestricted by field of view or low sampling rate, this novel approach provides a means to measure kinematic patterns that elevate ACL strains and that provide new insights into ACL injury mechanisms.     

Assessment of Cardiac Function and Myocardial Morphology Using Small Animal Look-locker Inversion Recovery (SALLI) MRI in Rats

Small animal magnetic resonance imaging is an important tool to study cardiac function and changes in myocardial tissue. The high heart rates of small animals (200 to 600 beats/min) have previously limited the role of CMR imaging. Small animal Look-Locker inversion recovery (SALLI) is a T1 mapping sequence for small animals to overcome this problem ¹. T1 maps provide quantitative information about tissue alterations and contrast agent kinetics. It is also possible to detect diffuse myocardial processes such as interstitial fibrosis or edema ^1-6. Furthermore, from a single set of image data, it is possible to examine heart function and myocardial scarring by generating cine and inversion recovery-prepared late gadolinium enhancement-type MR images ¹.The presented video shows step-by-step the procedures to perform small animal CMR imaging. Here it is presented with a healthy Sprague-Dawley rat, however naturally it can be extended to different cardiac small animal models.     

First combined in vivo X-ray tomography and high-resolution molecular electron paramagnetic resonance (EPR) imaging of the mouse knee joint taking into account the disappearance kinetics of the EPR probe

Although laboratory data clearly suggest a role for oxidants (dioxygen and free radicals derived from dioxygen) in the pathogenesis of many age-related and degenerative diseases (such as arthrosis and arthritis), methods to image such species in vivo are still very limited. This methodological problem limits physiopathologic studies about the role of those species in vivo, the effects of their regulation using various drugs, and the evaluation of their levels for diagnosis of degenerative diseases. In vivo electron paramagnetic resonance (EPR) imaging and spectroscopy are unique, noninvasive methods used to specifically detect and quantify paramagnetic species. However, two problems limit their application: the anatomic location of the EPR image in the animal body and the relative instability of the EPR probes. Our aim is to use EPR imaging to obtain physiologic and pathologic information on the mouse knee joint. This article reports the first in vivo EPR image of a small tissue, the mouse knee joint, with good resolution (≈ 160 μm) after intra-articular injection of a triarylmethyl radical EPR probe. It was obtained by combining EPR and x-ray micro-computed tomography for the first time and by taking into account the disappearance kinetics of the EPR probe during image acquisition to reconstruct the image. This multidisciplinary approach opens the way to high-resolution EPR imaging and local metabolism studies of radical species in vivo in different physiologic and pathologic situations.     

Construction of 3D human distal femoral surface models using a 3D statistical deformable model

Construction of 3D geometric surface models of human knee joint is always a challenge in biomedical engineering. This study introduced an improved statistical shape model (SSM) method that only uses 2D images of a joint to predict the 3D joint surface model. The SSM was constructed using 40 distal femur models of human knees. In this paper, a series validation and parametric analysis suggested that more than 25 distal femur models are needed to construct the SSM; each distal femur should be described using at least 3000 nodes in space; and two 2D fluoroscopic images taken in 45° directions should be used for the 3D surface shape prediction. Using this SSM method, ten independent distal femurs from 10 independent living subjects were predicted using their 2D plane fluoroscopic images. The predicted models were compared to their native 3D distal femur models constructed using their 3D MR images. The results demonstrated that using two fluoroscopic images of the knee, the overall difference between the predicted distal femur surface and the MR image-based surface was 0.16±1.16 mm. These data indicated that the SSM method could be a powerful method for construction of 3D surface geometries of the distal femur.     

A musculoskeletal finite element model of rat knee joint for evaluating cartilage biomechanics during gait

Abnormal loading of the knee due to injuries or obesity is thought to contribute to the development of osteoarthritis (OA). Small animal models have been used for studying OA progression mechanisms. However, numerical models to study cartilage responses under dynamic loading in preclinical animal models have not been developed. Here we present a musculoskeletal finite element model of a rat knee joint to evaluate cartilage biomechanical responses during a gait cycle. The rat knee joint geometries were obtained from a 3-D MRI dataset and the boundary conditions regarding loading in the joint were extracted from a musculoskeletal model of the rat hindlimb. The fibril-reinforced poroelastic (FRPE) properties of the rat cartilage were derived from data of mechanical indentation tests. Our numerical results showed the relevance of simulating anatomical and locomotion characteristics in the rat knee joint for estimating tissue responses such as contact pressures, stresses, strains, and fluid pressures. We found that the contact pressure and maximum principal strain were virtually constant in the medial compartment whereas they showed the highest values at the beginning of the gait cycle in the lateral compartment. Furthermore, we found that the maximum principal stress increased during the stance phase of gait, with the greatest values at midstance. We anticipate that our approach serves as a first step towards investigating the effects of gait abnormalities on the adaptation and degeneration of rat knee joint tissues and could be used to evaluate biomechanically-driven mechanisms of the progression of OA as a consequence of joint injury or obesity.     

The effects of femoral graft placement on cartilage thickness after anterior cruciate ligament reconstruction

Altered joint motion has been thought to be a contributing factor in the long-term development of osteoarthritis after ACL reconstruction. While many studies have quantified knee kinematics after ACL injury and reconstruction, there is limited in vivo data characterizing the effects of altered knee motion on cartilage thickness distributions. Thus, the objective of this study was to compare cartilage thickness distributions in two groups of patients with ACL reconstruction: one group in which subjects received a non-anatomic reconstruction that resulted in abnormal joint motion and another group in which subjects received an anatomically placed graft that more closely restored normal knee motion. Ten patients with anatomic graft placement (mean follow-up: 20 months) and 12 patients with non-anatomic graft placement (mean follow-up: 18 months) were scanned using high-resolution MR imaging. These images were used to generate 3D mesh models of both knees of each patient. The operative and contralateral knee models were registered to each other and a grid sampling system was used to make site-specific comparisons of cartilage thickness. Patients in the non-anatomic graft placement group demonstrated a significant decrease in cartilage thickness along the medial intercondylar notch in the operative knee relative to the intact knee (8%). In the anatomic graft placement group, no significant changes were observed. These findings suggest that restoring normal knee motion after ACL injury may help to slow the progression of degeneration. Therefore, graft placement may have important implications on the development of osteoarthritis after ACL reconstruction.     

Variability of a three-dimensional finite element model constructed using magnetic resonance images of a knee for joint contact stress analysis

Magnetic resonance (MR) imaging has been widely used to evaluate the thickness and volume of articular cartilage both in vivo and in vitro. While morphological information on the cartilage can be obtained using MR images, image processing for extracting geometric boundaries of the cartilage may introduce variations in the thickness of the cartilage. To evaluate the variability of using MR images to construct finite element (FE) knee cartilage models, five investigators independently digitized the same set of MR images of a human knee. The topology of cartilage thickness was determined using a minimal distance algorithm. Less than 8 percent variation in cartilage thickness was observed from the digitized data. The effect of changes in cartilage thickness on contact stress analysis was then investigated using five FE models of the knee. One FE model (average FE model) was constructed using the mean values of the digitized contours of the cartilage, and the other four were constructed by varying the thickness of the average FE model by +/- 5 percent and +/- 10 percent, respectively. The results demonstrated that under axial tibial compressive loading (up to 1,400 N), variations of cartilage thickness caused by digitization of MR images may result in a difference of approximately 10 percent in peak contact stresses (surface pressure, von Mises stress, and hydrostatic pressure) in the cartilage. A reduction of cartilage thickness caused increases of contact stresses, while an increase of cartilage thickness reduced contact stresses. Furthermore, the effect of variation of material properties of the cartilage on contact stress analysis was investigated. The peak contact stress increased almost linearly with the Young's modulus of the cartilage. The peak von Mises stress was dramatically reduced when the Poisson,s ratio was increased from 0.05 to 0.49 under an axial compressive load of 1,400 N, while peak hydrostatic pressure was dramatically increased. Peak surface pressure was also increased with the Poisson's ratio, but with a lower magnitude compared to von Mises stress and hydrostatic pressure. In conclusion, the imaging process may cause 10 percent variations in peak contact stress, and the predicted stress distribution is sensitive to the accuracy of the material properties of the cartilage model, especially to the variation of Poisson's ratio.     

A validated three-dimensional computational model of a human knee joint

This paper presents a three-dimensional finite element tibio-femoral joint model of a human knee that was validated using experimental data. The geometry of the joint model was obtained from magnetic resonance (MR) images of a cadaveric knee specimen. The same specimen was biomechanically tested using a robotic/universal force-moment sensor (UFS) system and knee kinematic data under anterior-posterior tibial loads (up to 100 N) were obtained. In the finite element model (FEM), cartilage was modeled as an elastic material, ligaments were represented as nonlinear elastic springs, and menisci were simulated by equivalent-resistance springs. Reference lengths (zero-load lengths) of the ligaments and stiffness of the meniscus springs were estimated using an optimization procedure that involved the minimization of the differences between the kinematics predicted by the model and those obtained experimentally. The joint kinematics and in-situ forces in the ligaments in response to axial tibial moments of up to 10 Nm were calculated using the model and were compared with published experimental data on knee specimens. It was also demonstrated that the equivalent-resistance springs representing the menisci are important for accurate calculation of knee kinematics. Thus, the methodology developed in this study can be a valuable tool for further analysis of knee joint function and could serve as a step toward the development of more advanced computational knee models.     

Cranial MRI of small rodents using a clinical MR scanner

Increasing numbers of small animal models are in use in the field of neuroscience research. Magnetic resonance imaging (MRI) provides an excellent method for non-invasive imaging of the brain. Using three-dimensional (3D) MR sequences allows lesion volumetry, e.g. for the quantification of tumor size. Specialized small-bore animal MRI scanners are available for high-resolution MRI of small rodents' brain, but major drawbacks of this dedicated equipment are its high costs and thus its limited availability. Therefore, more and more research groups use clinical MR scanners for imaging small animal models. But to achieve a reasonable spatial resolution at an acceptable signal-to-noise ratio with these scanners, some requirements concerning sequence parameters have to be matched. Thus, the aim of this paper was to present in detail a method how to perform MRI of small rodents brain using a standard clinical 1.5 T scanner and clinically available radio frequency coils to keep material costs low and to circumvent the development of custom-made coils.     

Multi-body optimization with subject-specific knee models: performance at high knee flexion angles

When estimating knee kinematics from skin markers and stereophotogrammetry, multi-body optimization (MBO) has provided promising results for reducing soft tissue artefacts (STA), but can still be improved. The goal of this study was to assess the performance of MBO with subject-specific knee models at high knee flexion angles (up to 110°) against knee joint kinematics measured by magnetic resonance imaging. Eight subjects were recruited. MBO with subject-specific knee models was more effective in compensating STA compared to no kinematic and spherical constraints, in particular for joint displacements. Moreover, it seems to be more reliable over large ranges of knee flexion angle. The ranges of root mean square errors for knee rotations/displacements were 3.0°–9.2°/1.3–3.5 mm for subject-specific knee models, 6.8°–8.7°/6.0–12.4 mm without kinematic constraint and 7.1°–9.8°/4.9–12.5 mm for spherical constraints.     

Integrating modelling, motion capture and x-ray fluoroscopy to investigate patellofemoral function during dynamic activity

Accurate measurement of knee-joint kinematics is critical for understanding the biomechanical function of the knee in vivo. Measurements of the relative movements of the bones at the knee are often used in inverse dynamics analyses to estimate the net muscle torques exerted about the joint, and as inputs to finite-element models to accurately assess joint contact. The fine joint translations that contribute to patterns of joint stress are impossible to measure accurately using traditional video-based motion capture techniques. Sub-millimetre changes in joint translation can mean the difference between contact and no contact of the cartilage tissue, leading to incorrect predictions of joint loading. This paper describes the use of low-dose X-ray fluoroscopy, an in vivo dynamic imaging modality that is finding increasing application in human joint motion measurement. Specifically, we describe a framework that integrates traditional motion capture, X-ray fluoroscopy and anatomically-based finite-element modelling for the purpose of assessing joint function during dynamic activity. We illustrate our methodology by applying it to study patellofemoral joint function, wherein the relative movements of the patella are predicted and the corresponding joint-contact stresses are calculated for a step-up task.     

Does a specific MR imaging protocol with a supine-lying subject replicate tarsal kinematics seen during upright standing?

Magnetic resonance (MR) imaging is becoming increasingly important in the study of foot biomechanics. Specific devices have been constructed to load and position the foot while the subject is lying supine in the scanner. The present study examines the efficacy of such a newly developed device in replicating tarsal kinematics seen during the more commonly studied standing loading conditions. The results showed that although knee flexion and the externally applied load were carefully controlled, subtalar and talo-navicular joint rotations while lying during MR imaging and when standing (measured opto-electrically with markers attached to intracortical pins) did not match, nor were they systematically shifted. Thus, the proposed MR protocol cannot replicate tarsal kinematics seen during upright standing. It is concluded that specific foot loading conditions have to be considered when tarsal kinematics are evaluated. Improved replication of tarsal kinematics in different postures should comprehensively consider muscle activity, a fixed hip position, and a well-defined point of load application.     

The In-Vivo Use of Superparamagnetic Iron Oxide Nanoparticles to Detect Inflammation Elicits a Cytokine Response but Does Not Aggravate Experimental Arthritis

BackgroundSuperparamagnetic Iron Oxide Nanoparticles (SPION) are used in diagnostic imaging of a variety of different diseases. For such in-vivo application, an additional coating with a polymer, for example polyvinyl alcohol (PVA), is needed to stabilize the SPION and prevent aggregation. As the particles are foreign to the body, reaction against the SPION could occur. In this study we investigated the effects that SPION may have on experimental arthritis after intra-articular (i.a.) or intravenous (i.v.) injection.MethodsPVA-coated SPION were injected either i.a. (6 or 24 μg iron) or i.v. (100 μg or 1 mg iron) into naïve Toll-like receptor-4 deficient (TLR4-/-) or wild-type C57Bl/6 mice, or C57Bl/6 mice with antigen-induced arthritis. As control, some mice were injected with PVA or PBS. MR imaging was performed at 1 and 7 days after injection. Mice were sacrificed 2 hours and 1, 2, 7, 10 and 14 days after injection of the SPION, and RNA from synovium and liver was isolated for pro-inflammatory gene expression analysis. Serum cytokine measurements and whole knee joint histology were also performed.ResultsInjection of a high dose of SPION or PVA into naïve knee joints resulted in an immediate upregulation of pro-inflammatory gene expression in the synovium. A similar gene expression profile was observed after SPION or PVA injection into knee joints of TLR4-/- mice, indicating that this effect is not due to LPS contamination. Histological analysis of the knee joints also revealed synovial inflammation after SPION injection. Two hours after i.v. injection of SPION or PVA into naïve mice, an upregulation of pro-inflammatory gene expression was detected in the liver. Administration of SPION or PVA into arthritic mice via i.a. injection did not result in an upregulation in gene expression and also no additional effects were observed on histology. MR imaging and histology showed long-term retention of SPION in the inflamed joint. However, 14 days after the injections no long-term effects were evident for gene expression, histology or serum cytokine concentrations.ConclusionsInjection of SPION, either locally or systemically, gives an acute inflammatory response. In the long term, up to 14 days after the injection, while the SPION reside in the joint, no further activating effects of SPION were observed. Hence, we conclude that SPION do not aggravate arthritis and can therefore be used safely to detect joint inflammation by MR imaging.     

Experimental nerve imaging at 1.5-T

Experimental lesions of the peripheral nerve system can be visualized in vivo by magnetic resonance imaging (MRI). Many studies of the rat peripheral nervous systems were performed on dedicated animal MR scanners with a high magnetic field strength for good spatial resolution. Here, we present an MR protocol to study experimental lesions of the rat nervous system with clinical 1.5-T MR scanners and commercially available coils. Using a three-sequence approach (T1-weighted imaging, fat-saturated T2-weighted imaging and fat-saturated T1-weighted imaging with Gd-DTPA in the same plane), the relevant signal changes of the lesioned nerve can be visualized and separated from other structures, e.g., blood vessels. Furthermore, we give an overview on different types of contrast agents used for peripheral nerve MR imaging and MR findings in selected experimental models of rat peripheral nerve injury.     

Cardiovascular applications of magnetic resonance imaging

Magnetic resonance (MR) imaging is a unique imaging modality that is gaining rapid acceptance for a variety of medical indications. Diagnostic information is obtained noninvasively, without the potential hazards of ionizing radiation. The spatial resolution and anatomic detail of MR imaging rival those of other currently available imaging methods. By gating to an electrocardiographic signal cardiac imaging is possible. Since March 1983 the authors have had experience with cardiac MR imaging in both animals and humans. Cardiac anatomy is well shown by this technique, which allows detection and characterization of intracardiac masses, congenital heart disease and anomalies of the great vessels. Myocardial infarction has been detected in both animals and humans without the use of contrast agents, and acute cardiac transplant rejection has been visualized in an animal model. Limitations of MR imaging primarily have been lengthy imaging times and the sensitivity of the images to motion. With further investigation and experience this technique may become useful for studying a wide variety of cardiovascular disorders.     

Image based weighted center of proximity versus directly measured knee contact location during simulated gait

To understand the mechanical consequences of knee injury requires a detailed analysis of the effect of that injury on joint contact mechanics during activities of daily living. Three-dimensional (3D) knee joint geometric models have been combined with knee joint kinematics to dynamically estimate the location of joint contact during physiological activities—using a weighted center of proximity (WCoP) method. However, the relationship between the estimated WCoP and the actual location of contact has not been defined. The objective of this study was to assess the relationship between knee joint contact location as estimated using the image-based WCoP method, and a directly measured weighted center of contact (WCoC) method during simulated walking. To achieve this goal, we created knee specific models of six human cadaveric knees from magnetic resonance imaging. All knees were then subjected to physiological loads on a knee simulator intended to mimic gait. Knee joint motion was captured using a motion capture system. Knee joint contact stresses were synchronously recorded using a thin electronic sensor throughout gait, and used to compute WCoC for the medial and lateral plateaus of each knee. WCoP was calculated by combining knee kinematics with the MRI-based knee specific model. Both metrics were compared throughout gait using linear regression. The anteroposterior (AP) location of WCoP was significantly correlated with that of WCoC on both tibial plateaus in all specimens (p<0.01, 95% confidence interval of Pearson?s coefficient r>0), but the correlation was not significant in the mediolateral (ML) direction for 4/6 knees (p>0.05). Our study demonstrates that while the location of joint contact obtained from 3D knee joint contact model, using the WCoP method, is significantly correlated with the location of actual contact stresses in the AP direction, that relationship is less certain in the ML direction.     

Computational analysis of knee joint stability following total knee arthroplasty

The overall objective of this study was to introduce knee joint power as a potential measure to investigate knee joint stability following total knee arthroplasty (TKA). Specific aims were to investigate whether weakened knee joint stabilizers cause abnormal kinematics and how it influences the knee joint kinetic (i.e., power) in response to perturbation.Patient-specific musculoskeletal models were simulated with experimental gait data from six TKA patients (baseline models). Muscle strength and ligament force parameter were reduced by up to 30% to simulate weak knee joint stabilizers (weak models). Two different muscle recruitment criteria were tested to examine whether altered muscle recruitment pattern can mask the influence of weakened stabilizers on the knee joint kinematics and kinetics. Level-walking knee joint kinematics and kinetics were calculated though force-dependent kinematic and inverse dynamic analyses. Bode analysis was then recruited to estimate the knee joint power in response to a simulated perturbation.Weak models resulted in larger anterior-posterior (A-P) displacement and internal-external (I-E) rotation compared to baseline (I-E: 18.4 ± 8.5 vs. 11.6 ± 5.7 (deg), A-P: 9.7 ± 5.6 vs. 5.5 ± 4.1 (mm)). Changes in muscle recruitment criterion however altered the results such that A-P and I-E were not notably different from baseline models. In response to the simulated perturbation, weak models versus baseline models generated a delayed power response with unbounded magnitudes. Perturbed power behavior of the knee remained unaltered regardless of the muscle recruitment criteria.In conclusion, impairment at the knee joint stabilizers may or may not lead to excessive joint motions but it notably affects the knee joint power in response to a perturbation. Whether perturbed knee joint power is associated with the patient-reported outcome requires further investigation.     

Statistical shape model-based prediction of tibiofemoral cartilage

Abstract

Computed tomography is used more routinely to design patient-specific instrumentation for knee replacement surgery. Its moderate imaging cost and simplified segmentation reduce design costs compared with magnetic resonance (MR) imaging, but it cannot provide the necessary cartilage information. Our method based on statistical shape modelling proved to be successful in predicting tibiofemoral cartilage in leave-one-out experiments. The obtained accuracy of 0.54?mm for femur and 0.49?mm for tibia outperforms the average cartilage thickness distribution and reported inter-observer MR segmentation variability. These results suggest that shape modelling is able to predict tibiofemoral cartilage with sufficient accuracy to design patient-specific instrumentation.