In vivo ankle joint kinematics from dynamic magnetic resonance imaging using a registration-based framework

In this paper, we propose a method for non-invasively measuring three-dimensional in vivo kinematics of the ankle joint from a dynamic MRI acquisition of a single range-of-motion cycle. The proposed approach relies on an intensity-based registration method to estimate motion from multi-plane dynamic MRI data. Our approach recovers not only the movement of the skeleton, but also the possibly non-rigid temporal deformation of the joint. First, the rigid motion of each ankle bone is estimated. Second, a four-dimensional (3D+time) high-resolution dynamic MRI sequence is estimated through the use of the log-euclidean framework for the computation of temporal dense deformation fields. This approach has been then applied and evaluated on in vivo dynamic MRI data acquired for a pilot study on six healthy pediatric cohort in order to establish in vivo normative joint biomechanics. Results demonstrate the robustness of the proposed pipeline and very promising high resolution visualization of the ankle joint.     

MRI vs CT-based 2D-3D auto-registration accuracy for quantifying shoulder motion using biplane video-radiography

Biplane 2D-3D registration approaches have been used for measuring 3D, in vivo glenohumeral (GH) joint kinematics. Computed tomography (CT) has become the gold standard for reconstructing 3D bone models, as it provides high geometric accuracy and similar tissue contrast to video-radiography. Alternatively, magnetic resonance imaging (MRI) would not expose subjects to radiation and provides the ability to add cartilage and other soft tissues to the models. However, the accuracy of MRI-based 2D-3D registration for quantifying glenohumeral kinematics is unknown. We developed an automatic 2D-3D registration program that works with both CT- and MRI-based image volumes for quantifying joint motions. The purpose of this study was to use the proposed 2D-3D auto-registration algorithm to describe the humerus and scapula tracking accuracy of CT- and MRI-based registration relative to radiostereometric analysis (RSA) during dynamic biplanar video-radiography. The GH kinematic accuracy (RMS error) was 0.6–1.0 mm and 0.6–2.2° for the CT-based registration and 1.4–2.2 mm and 1.2–2.6° for MRI-based registration. Higher kinematic accuracy of CT-based registration was expected as MRI provides lower spatial resolution and bone contrast as compared to CT and suffers from spatial distortions. However, the MRI-based registration is within an acceptable accuracy for many clinical research questions.     

A simple but reliable method for measuring 3D Achilles tendon moment arm geometry from a single,static magnetic resonance scan

Current methods for measuring in vivo 3D muscle-tendon moment arms generally rely on the acquisition of magnetic resonance imaging (MRI) scans at multiple joint angles. However, for patients with musculoskeletal pathologies such as fixed contractures, moving a joint through its full range of motion is not always feasible. The purpose of this research was to develop a simple, but reliable in vivo 3D Achilles tendon moment arm (ATMA) technique from a single static MRI scan. To accomplish this, for nine healthy adults (5 males, 4 females), the geometry of a cylinder was fit to the 3D form of the talus dome, which was used to estimate the talocrural flexion/extension axis, and a fifth-order polynomial fit to the line of action of the Achilles tendon. The single static scan in vivo 3D ATMA estimates were compared to estimates obtained from the same subjects at the same ankle joint angles using a previously validated 3D dynamic MRI based in vivo ATMA measurement technique. The ATMA estimates from the single scan in vivo 3D method (52.5 mm ± 5.6) were in excellent agreement (ICC = 0.912) to the validated in vivo 3D method (51.5 mm ± 5.1). These data show reliable in vivo 3D ATMA can be obtained from a single MRI scan for healthy adult populations. The single scan, in vivo 3D ATMA technique provides researchers with a simple, but reliable method for obtaining subject-specific ATMAs for musculoskeletal modelling purposes.     

A comparison of patellofemoral cartilage morphology and deformation in anterior cruciate ligament deficient versus uninjured knees

Anterior cruciate ligament (ACL) deficient patients have an increased rate of patellofemoral joint (PFJ) osteoarthritis (OA) as compared to the general population. Although the cause of post-injury OA is multi-factorial, alterations in joint biomechanics may predispose patients to cartilage degeneration. This study aimed to compare in vivo PFJ morphology and mechanics between ACL deficient and intact knees in subjects with unilateral ACL ruptures. Eight male subjects underwent baseline MRI scans of both knees. They then performed a series of 60 single-legged hops, followed by a post-exercise MRI scan. This process was repeated for the contralateral knee. The MR images were converted into three-dimensional surface models of cartilage and bone in order to assess cartilage thickness distributions and strain following exercise. Prior to exercise, patellar cartilage was significantly thicker in intact knees as compared to ACL deficient knees by 1.8%. In response to exercise, we observed average patellar cartilage strains of 5.4 ± 1.1% and 2.5 ± 1.4% in the ACL deficient and intact knees, respectively. Importantly, the magnitude of patellar cartilage strain in the ACL deficient knees was significantly higher than in the intact knees. However, while trochlear cartilage experienced a mean strain of 2.4 ± 1.6%, there was no difference in trochlear cartilage strain between the ACL deficient and uninjured knees. In summary, we found that ACL deficiency was associated with decreased patellar cartilage thickness and increased exercise-induced patellar cartilage strain when compared to the uninjured contralateral knees.     

Robotic simulation of identical athletic-task kinematics on cadaveric limbs exhibits a lack of differences in knee mechanics between contralateral pairs

Limb asymmetry is a known factor for increased ACL injury risk. These asymmetries are normally observed during in vivo testing. Prior studies have developed in vitro testing methodologies driven by in vivo kinematics to investigate knee mechanics relative to ACL injury. The objective of this study was to determine if mechanical side-to-side asymmetries persist in contralateral pairs during in vitro simulation testing. In vivo kinematics were recorded for male and female drop vertical jump and sidestep cutting tasks. The recorded kinematics were used to robotically simulate the motions on 7 contralateral pairs of cadaveric lower extremities specimens. ACL and MCL force, torque, and strains were recorded and analyzed for differences between contralateral pairs. There was a general lack of mechanical differences between limb sides. Adduction peak torque for the male sidestep cut movement was significantly different between limb sides (p=0.04). However, this is consistent with ACL injury mechanics in that movement in the frontal plane (abduction/adduction) increases injury risk and it is possible loading differences in this plane may have resulted from tolerances within the setup process. The findings of this study indicate that contralateral knee joints were representative of each other during biomechanical in vitro tests. In future cadaveric robotic simulations, contralateral limbs can be used interchangeably. In addition, direct comparisons of the structural behaviors of isolated conditions for contralateral knee joints can be performed.     

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.     

Direct contribution of axial impact compressive load to anterior tibial load during simulated ski landing impact

Anterior tibial loading is a major factor involved in the anterior cruciate ligament (ACL) injury mechanism during ski impact landing. We sought to investigate the direct contribution of axial impact compressive load to anterior tibial load during simulated ski landing impact of intact knee joints without quadriceps activation. Twelve porcine knee specimens were procured. Four specimens were used as non-impact control while the remaining eight were mounted onto a material-testing system at 70° flexion and subjected to simulated landing impact, which was successively repeated with incremental actuator displacement. Four specimens from the impacted group underwent pre-impact MRI for tibial plateau angle measurements while the other four were subjected to histology and microCT for cartilage morphology and volume assessment. The tibial plateau angles ranged from 29.4 to 38.8°. There was a moderate linear relationship (Y=0.16X; R²=0.64; p<0.001) between peak axial impact compressive load (Y) and peak anterior tibial load (X). The anterior and posterior regions in the impacted group sustained surface cartilage fraying, superficial clefts and tidemark disruption, compared to the control group. MicroCT scans displayed visible cartilage deformation for both anterior and posterior regions in the impacted group. Due to the tibial plateau angle, increased axial impact compressive load can directly elevate anterior tibial load and hence contribute to ACL failure during simulated landing impact. Axial impact compressive load resulted in shear cartilage damage along anterior–posterior tibial plateau regions, due to its contribution to anterior tibial loading. This mechanism plays an important role in elevating ACL stress and cartilage deformation during impact landing.     

Static and dynamic error of a biplanar videoradiography system using marker-based and markerless tracking techniques

The use of biplanar videoradiography technology has become increasingly popular for evaluating joint function in vivo. Two fundamentally different methods are currently employed to reconstruct 3D bone motions captured using this technology. Marker-based tracking requires at least three radio-opaque markers to be implanted in the bone of interest. Markerless tracking makes use of algorithms designed to match 3D bone shapes to biplanar videoradiography data. In order to reliably quantify in vivo bone motion, the systematic error of these tracking techniques should be evaluated. Herein, we present new markerless tracking software that makes use of modern GPU technology, describe a versatile method for quantifying the systematic error of a biplanar videoradiography motion capture system using independent gold standard instrumentation, and evaluate the systematic error of the W.M. Keck XROMM Facility's biplanar videoradiography system using both marker-based and markerless tracking algorithms under static and dynamic motion conditions. A polycarbonate flag embedded with 12 radio-opaque markers was used to evaluate the systematic error of the marker-based tracking algorithm. Three human cadaveric bones (distal femur, distal radius, and distal ulna) were used to evaluate the systematic error of the markerless tracking algorithm. The systematic error was evaluated by comparing motions to independent gold standard instrumentation. Static motions were compared to high accuracy linear and rotary stages while dynamic motions were compared to a high accuracy angular displacement transducer. Marker-based tracking was shown to effectively track motion to within 0.1?mm and 0.1 deg under static and dynamic conditions. Furthermore, the presented results indicate that markerless tracking can be used to effectively track rapid bone motions to within 0.15 deg for the distal aspects of the femur, radius, and ulna. Both marker-based and markerless tracking techniques were in excellent agreement with the gold standard instrumentation for both static and dynamic testing protocols. Future research will employ these techniques to quantify in vivo joint motion for high-speed upper and lower extremity impacts such as jumping, landing, and hammering.     

The effect of isolated valgus moments on ACL strain during single-leg landing: A simulation study

Valgus moments on the knee joint during single-leg landing have been suggested as a risk factor for anterior cruciate ligament (ACL) injury. The purpose of this study was to test the influence of isolated valgus moment on ACL strain during single-leg landing. Physiologic levels of valgus moments from an in vivo study of single-leg landing were applied to a three-dimensional dynamic knee model, previously developed and tested for ACL strain measurement during simulated landing. The ACL strain, knee valgus angle, tibial rotation, and medial collateral ligament (MCL) strain were calculated and analyzed. The study shows that the peak ACL strain increased nonlinearly with increasing peak valgus moment. Subjects with naturally high valgus moments showed greater sensitivity for increased ACL strain with increased valgus moment, but ACL strain plateaus below reported ACL failure levels when the applied isolated valgus moment rises above the maximum values observed during normal cutting activities. In addition, the tibia was observed to rotate externally as the peak valgus moment increased due to bony and soft-tissue constraints. In conclusion, knee valgus moment increases peak ACL strain during single-leg landing. However, valgus moment alone may not be sufficient to induce an isolated ACL tear without concomitant damage to the MCL, because coupled tibial external rotation and increasing strain in the MCL prevent proportional increases in ACL strain at higher levels of valgus moment. Training that reduces the external valgus moment, however, can reduce the ACL strain and thus may help athletes reduce their overall ACL injury risk.     

3D Evaluation of the acetabular coverage assessed by biplanar X-rays or single anteroposterior X-ray compared with CT-scan

Considering the increasing development of three dimensional (3D) imaging, the 3D assessment of the acetabular coverage is to become the most interesting tool for the detection of acetabular pathologies. Biplanar X-rays based methods allow a 3D reconstruction of the hip with a reduced radiation dose. This study proposes a 3D assessment method of the acetabular coverage from biplanar X-rays or from an anteroposterior X-ray (conventional clinical imaging). An in vitro evaluation of the method was performed on six hip joints in comparison with computed tomography. The global coverage, the local coverage and the acetabular rim orientation were estimated in 3D. The mean global acetabular coverage was 40% with an estimated mean accuracy of 1.3% for the biplanar X-rays based method. This study evaluated a 3D assessment method of the acetabular coverage from biplanar X-rays or anteroposterior X-ray and open the way for clinical in vivo applications.     

Facilitating tumor functional assessment by spatially relating 3D tumor histology and in vivo MRI: image registration approach

Background

Magnetic resonance imaging (MRI), together with histology, is widely used to diagnose and to monitor treatment in oncology. Spatial correspondence between these modalities provides information about the ability of MRI to characterize cancerous tissue. However, registration is complicated by deformations during pathological processing, and differences in scale and information content.

Methodology/Principal Findings

This study proposes a methodology for establishing an accurate 3D relation between histological sections and high resolution in vivo MRI tumor data. The key features of the methodology are: 1) standardized acquisition and processing, 2) use of an intermediate ex vivo MRI, 3) use of a reference cutting plane, 4) dense histological sampling, 5) elastic registration, and 6) use of complete 3D data sets. Five rat pancreatic tumors imaged by T2*-w MRI were used to evaluate the proposed methodology. The registration accuracy was assessed by root mean squared (RMS) distances between manually annotated landmark points in both modalities. After elastic registration the average RMS distance decreased from 1.4 to 0.7 mm. The intermediate ex vivo MRI and the reference cutting plane shared by all three 3D images (in vivo MRI, ex vivo MRI, and 3D histology data) were found to be crucial for the accurate co-registration between the 3D histological data set and in vivo MRI. The MR intensity in necrotic regions, as manually annotated in 3D histology, was significantly different from other histologically confirmed regions (i.e., viable and hemorrhagic). However, the viable and the hemorrhagic regions showed a large overlap in T2^*-w MRI signal intensity.

Conclusions

The established 3D correspondence between tumor histology and in vivo MRI enables extraction of MRI characteristics for histologically confirmed regions. The proposed methodology allows the creation of a tumor database of spatially registered multi-spectral MR images and multi-stained 3D histology.     

Quantifying in vivo laxity in the anterior cruciate ligament and individual knee joint structures

A custom knee loading apparatus (KLA), when used in conjunction with magnetic resonance imaging, enables in vivo measurement of the gross anterior laxity of the knee joint. A numerical model was applied to the KLA to understand the contribution of the individual joint structures and to estimate the stiffness of the anterior-cruciate ligament (ACL). The model was evaluated with a cadaveric study using an in situ knee loading apparatus and an ElectroForce test system. A constrained optimization solution technique was able to predict the restraining forces within the soft-tissue structures and joint contact. The numerical model presented here allowed in vivo prediction of the material stiffness parameters of the ACL in response to applied anterior loading. Promising results were obtained for in vivo load sharing within the structures. The numerical model overestimated the ACL forces by 27.61–92.71%. This study presents a novel approach to estimate ligament stiffness and provides the basis to develop a robust and accurate measure of in vivo knee joint laxity.     

Monitoring the effects of dexamethasone treatment by MRI using in vivo iron oxide nanoparticle-labeled macrophages

Introduction

Rheumatoid arthritis (RA) is a chronic disease causing recurring inflammatory joint attacks. These attacks are characterized by macrophage infiltration contributing to joint destruction. Studies have shown that RA treatment efficacy is correlated to synovial macrophage number. The aim of this study was to experimentally validate the use of in vivo superparamagnetic iron oxide nanoparticle (SPION) labeled macrophages to evaluate RA treatment by MRI.

Methods

The evolution of macrophages was monitored with and without dexamethasone (Dexa) treatment in rats. Two doses of 3 and 1 mg/kg Dexa were administered two and five days following induction of antigen induced arthritis. SPIONs (7 mg Fe/rat) were injected intravenously and the knees were imaged in vivo on days 6, 10 and 13. The MR images were scored for three parameters: SPION signal intensity, SPION distribution pattern and synovial oedema. Using 3D semi-automated software, the MR SPION signal was quantified. The efficacy of SPIONs and gadolinium chelate (Gd), an MR contrast agent, in illustrating treatment effects were compared. Those results were confirmed through histological measurements of number and area of macrophages and nanoparticle clusters using CD68 immunostaining and Prussian blue staining respectively.

Results

Results show that the pattern and the intensity of SPION-labeled macrophages on MRI were altered by Dexa treatment. While the Dexa group had a uniform elliptical line surrounding an oedema pocket, the untreated group showed a diffused SPION distribution on day 6 post-induction. Dexa reduced the intensity of SPION signal 50-60% on days 10 and 13 compared to controls (P = 0.00008 and 0.002 respectively). Similar results were found when the signal was measured by the 3D tool. On day 13, the persisting low grade arthritis progression could not be demonstrated by Gd. Analysis of knee samples by Prussian blue and CD68 immunostaining confirmed in vivo SPION uptake by macrophages. Furthermore, CD68 immunostaining revealed that Dexa treatment significantly decreased the area and number of synovial macrophages. Prussian blue quantification corresponded to the macrophage measurements and both were in agreement with the MRI findings.

Conclusions

We have demonstrated the feasibility of MRI tracking of in vivo SPION-labeled macrophages to assess RA treatment effects.     

Three-dimensional collective cell motions in an acinus-like lumen

Collective cell migration is an essential process in embryo development, wound healing, inflammatory response, and cancer invasion. Although cell motions in two-dimensional (2D) monolayers have been studied previously, three-dimensional (3D) collective cell migration, which constantly occurs during embryogenesis such as the establishment of ducts and acini in vivo, remains elusive. In this paper, we develop a cell-based model incorporating cell mechanics and cell motility to address coherent cell motions in a spherical acinus-like lumen with different cell populations. It is found that the interplays between cell persistence, random fluctuation, and geometrical confinement may engender rich and novel migratory modes. In a 3D spherical lumen, two cells may undergo stripe-like or cross-circular coherent rotations, whereas multiple cells can form dynamic twisting or circulating bands, leaving sparse cells at the center or even a hollow cavity in the cell aggregate. The cell density is found to profoundly influence the collective cell migration modes. Our model can reproduce the fundamental features observed in experiments and highlight the role of mechanics in steering 3D collective cell dynamics during mammary acinar morphogenesis.     

Radiography used to measure internal spinal cord deformation in an in vivo rat model

Little is known about the internal mechanics of the in vivo spinal cord during injury. The objective of this study was to develop a method of tracking internal and surface deformation of in vivo rat spinal cord during compression using radiography. Since neural tissue is radio-translucent, radio-opaque markers were injected into the spinal cord.Two tantalum beads (260 µm) were injected into the cord (dorsal and ventral) at C5 of nine anesthetized rats. Four beads were glued to the lateral surface of the cord, caudal and cranial to the injection site. A compression plate was displaced 0.5 mm, 2 mm, and 3 mm into the spinal cord and lateral X-ray images were taken before, during, and after each compression for measuring bead displacements. Potential bead migration was monitored for by comparing displacements of the internal and glued surface beads.Dorsal beads moved significantly more than ventral beads with a range in averages of 0.57–0.71 mm and 0.31–0.35 mm respectively. Bead displacements during 0.5 mm compressions were significantly lower than 2 mm and 3 mm compressions. There was no statistically significant migration of the internal beads.The results indicate the merit of this technique for measuring in vivo spinal cord deformation. The pattern of bead displacements illustrates the complex internal and surface deformations of the spinal cord during transverse compression. This information is needed for validating physical and finite element spinal cord surrogates and to define relationships between loading parameters, internal cord deformation, and biological and functional outcomes.     

Derivatives of thiocolchicine and its applications to CEM cells treatment using F Magnetic Resonance ex vivo

It was shown, that cultured ex vivo human T-Lymphoblastoid (CEM) cells respond to synthesized thiocolchicine and fluorine thiocolchicine derivatives. The preparation of derivatives with substitution at C-3 and C-7 is described. All compounds were used at concentration from 1 nM to 1000 nM. Inhibitory effects of these compounds were examined in the three-dimensional (3-D) culture and cells morphology during treatment was monitored using 9.4 T MRI system. We performed studies of these compounds in CEM cells ex vivo using ¹H and ¹⁹F Magnetic Resonance Imaging (MRI), ¹⁹F Magnetic Resonance Spectroscopy (MRS), High Performance Liquid Chromatography coupled with Ultra Violet (HPLC-UV) and Electron Impact Mass Spectrometry (EIMS). The results of the multi-technique approach are consistent with the fact that the new derivatives are more efficient than colchicine and thiocolchicine ex vivo.     

The effect of femoral tunnel placement on ACL graft orientation and length during in vivo knee flexion

Anatomically placed grafts are believed to more closely restore the function of the ACL. This study measured the effect of femoral tunnel placement on graft orientation and length during weight-bearing flexion. Both knees of twelve patients where the graft was placed near the anteroproximal border of the ACL and ten where the graft was placed near the center of the ACL were imaged using MR. These images were used to create 3D models of the reconstructed and intact contralateral knees, including the attachment sites of the native ACL and graft. Next, patients were imaged using biplanar fluoroscopy while performing a quasi-static lunge. The models were registered to the fluoroscopic images to reproduce in vivo knee motion. From the relative motion of the attachment sites on the models, the length and orientation of the graft and native ACL were measured. Grafts placed anteroproximally on the femur were longer and more vertical than the native ACL in both the sagittal and coronal planes, while anatomically placed grafts more closely mimicked ACL motion. In full extension, the grafts placed anteroproximally were 12.3±5.2° (mean and 95%CI) more vertical than the native ACL in the sagittal plane, whereas the grafts placed anatomically were 2.9±3.7° less vertical. Grafts placed anteroproximally were up to 6±2 mm longer than the native ACL, while the anatomically placed grafts were a maximum of 2±2 mm longer. In conclusion, grafts placed anatomically more closely restored native ACL length and orientation. As a result, anatomic grafts are more likely to restore intact knee kinematics.     

3D Sequential Kinematics of the Femoro-Tibial Joint of Normal Knee from Multiple Bi-planar X-rays: Accuracy and Repeatability

Background

Several methods can be used to assess joint kinematics going from optoelectronic motion analysis to biplanar fluoroscopy. The aim of the present work was to evaluate the reliability of the use of biplane radiography to quantify the sequential 3D kinematics of the femoro-tibial joint.

Comparison of ACL strain estimated via a data-driven model with in vitro measurements

Computer modeling and simulation techniques have been increasingly used to investigate anterior cruciate ligament (ACL) loading during dynamic activities in an attempt to improve our understanding of injury mechanisms and development of injury prevention programs. However, the accuracy of many of these models remains unknown and thus the purpose of this study was to compare estimates of ACL strain from a previously developed three-dimensional, data-driven model with those obtained via in vitro measurements. ACL strain was measured as the knee was cycled from approximately 10° to 120° of flexion at 20 deg s^?1 with static loads of 100, 50, and 50 N applied to the quadriceps, biceps femoris and medial hamstrings (semimembranosus and semitendinosus) tendons, respectively. A two segment, five-degree-of-freedom musculoskeletal knee model was then scaled to match the cadaver’s anthropometry and in silico ACL strains were then determined based on the knee joint kinematics and moments of force. Maximum and minimum ACL strains estimated in silico were within 0.2 and 0.42% of that measured in vitro, respectively. Additionally, the model estimated ACL strain with a bias (mean difference) of ?0.03% and dynamic accuracy (rms error) of 0.36% across the flexion-extension cycle. These preliminary results suggest that the proposed model was capable of estimating ACL strains during a simple flexion-extension cycle. Future studies should validate the model under more dynamic conditions with variable muscle loading. This model could then be used to estimate ACL strains during dynamic sporting activities where ACL injuries are more common.