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The recently developed arthroscopic centralization for lateral meniscal extrusion has obtained satisfactory short-term clinical and radiological results and improves the meniscus biomechanical properties. However, the effectiveness of treatment for meniscus extrusion after partial meniscectomy still requires elucidation. This study investigated the effect of centralization with modifications from the mechanical viewpoint. Porcine knee joints (N=6) were set in a universal tester under the following conditions: 1) Intact; 2) Meniscectomy: inner half of the posterior half meniscus was removed; 3) Extrusion: posterior meniscus was dislocated laterally by transecting the posterior root and the meniscotibial ligament; 4) Centralization-1: centralization procedure using 1 anchor; 5) Centralization-2: centralization procedure using 2 anchors; 6) Centralization-ad: centralization with capsular advancement using 2 anchors. Load distributions and contact pressure in the meniscus and tibial cartilage were evaluated with an axial compressive force of 200 N. After meniscectomy, the tibial cartilage load increased and that of the medial margin of the posterior part of the meniscus decreased. When the meniscus was extruded, the load was concentrated only on the tibial cartilage. Centralization-1 increased the load on the meniscus, while Centralization-2 further increased the meniscus load but decreased the tibial cartilage load. Centralization-ad further decreased the load on the tibial plateau. The average contact pressure of the tibial cartilage was significantly higher in the Extrusion group than in the Intact group or the Centralization-ad group. From a biomechanical viewpoint, centralization with capsular advancement was the most effective of the tested procedures for treatment for an extruded meniscus after partial meniscectomy. This article is protected by copyright. All rights reserved.

Purpose This study aimed to establish the topographical and zonal T2 patterns of multi-resolution MRI in medial tibial cartilage in a canine model of osteoarthritis (OA), initiated by the anterior cruciate ligament (ACL) transection surgery, and studied after 8-weeks and 12-weeks post-surgery. Methods Articular cartilage from healthy, two stages of contralateral, and of OA knees were quantitatively imaged by the MRI T2 protocols at two imaging resolutions (100 and 17.6 μm/pixel). The zonal T2 changes at five topographical locations (anterior (AMT), exterior (EMT), posterior (PMT), central (CMT) and interior (IMT) medial tibia) and subsequent two averaged regions (covered by meniscus and exposed) were analyzed. At each location, full-thickness cartilage was studied in four sub-tissue zones (superficial, transitional, upper and lower radial zones). Results Tissue degradation can be detected by measurable changes of T2, which is resolution- and orientation-dependent. T2 changes ranging from +28.82% increase (SZ, PMT) to -23.15% decrease (RZ1, AMT) in healthy to disease (8C), with the largest increase of T2 in the surface tissue. Various location-dependent patterns of degradation are found over the tibial surface, most commonly shown in early-stage OA (8C) on the anterior site, different from the posterior. Finally, the contralateral cartilage has specific degradation patterns, different from those in OA cartilage. Conclusions This is the first quantitative and highest multi-resolution characterization of cartilage at five topographical locations over the medial tibial plateau with fine zonal resolution in an animal model of OA, which would benefit future investigation of human OA in clinics.

Relationships between composition, structure and constituent-specific functional properties of human articular cartilage at different stages of osteoarthritis (OA) are poorly known. We established these relationships by comparison of elastic, viscoelastic and fibril-reinforced poroelastic mechanical properties with microscopic and spectroscopic analysis of structure and composition of healthy and osteoarthritic human tibial cartilage (n = 27). At a low frequency (0.005 Hz), proteoglycan content correlated negatively and collagen content correlated positively with the phase difference (i.e. tissue viscosity). At a high-frequency regime (> 0.05 Hz), proteoglycan content correlated negatively and collagen orientation angle correlated positively with the phase difference. Proteoglycans were lost in the early and advanced OA groups compared to the healthy group, while the superficial collagen orientation angle was greater only in the advanced OA group compared to the healthy group. Simultaneously, the initial fibril network modulus (fibril pretension) was smaller in the early and advanced OA groups compared to the healthy group. These findings suggest different mechanisms contribute to cartilage viscosity in low and high frequencies, and that the loss of superficial collagen pretension during early OA is due to lower tissue swelling (PG loss), while in advanced OA, both collagen disorganization and lower swelling modulate the collagen fibril pretension. Electronic supplementary material The online version of this article (10.1007/s10439-020-02559-0) contains supplementary material, which is available to authorized users.

To use T2 relaxation time distribution profiles to assess inter-group regional differences along articular surfaces and to evaluate the feasibility of this analysis for comparison of cartilage insufficiency. Twelve pairs matched according to age and gender (12 healthy volunteers and 12 patients after anterior cruciate ligament reconstruction (ACLR)) underwent 3-T MRI. T2 maps were calculated from six time echo images of the mid-sagittal slice in the lateral and medial compartment. The femoral and tibial cartilage was analyzed by measuring T2 distribution profiles along the articular surfaces. T2 distribution profiles were generated along the length of the articular surface in the femorotibial compartments. Differences in the T2 distribution profiles between the tibial and femoral cartilage as well as between the cartilage of the femoral condyles were identified in healthy individuals. T2 distribution profiles clearly demonstrated cartilage insufficiency in the weight-bearing areas for subjects in the ACLR group. T2 distribution profiles can identify regional differences in femoral and tibial cartilage. The T2 distribution profile pattern is preserved with cartilage insufficiency, however, with important differences in T2 values for the ACLR group in weight-bearing areas.

Cartilage transmits and redistributes biomechanical loads in the knee joint during exercise. Exercise-induced loading alters cartilage hydration and is detectable using quantitative MRI, where T2 relaxation time (T2 ) is influenced by cartilage collagen composition, fiber orientation, and changes in extracellular matrix. This study characterized short-term transient responses of healthy knee cartilage to running-induced loading using bilateral scans and image registration. Eleven healthy female recreational runners (33.73±4.22 years) and four healthy female controls (27.25±1.38 years) were scanned on a 3T GE MRI scanner with qDESS before running over-ground (runner group) or resting (control group) for 40 minutes. Subjects were scanned immediately post-activity at five-minute intervals for 60 minutes. T2 times were calculated for femoral, tibial, and patellar cartilage at each time point and analyzed using a mixed-effects model and Bonferroni post-hoc. There were immediate decreases in T2 (mean±SEM) post-run in superficial femoral cartilage of at least 3.3±0.3% (P=0.002) between baseline and Time 0 that remained for 25 minutes, a decrease in superficial tibial cartilage T2 of 2.9±0.4% (P=0.041) between baseline and Time 0, and a decrease in superficial patellar cartilage T2 of 3.6±0.3% (P=0.020) 15 minutes post-run. There were decreases in the medial posterior region of superficial femoral cartilage T2 of at least 5.3±0.2% (P=0.022) within five minutes post-run that remained at 60 minutes post-run. Clinical Significance: These results increase understanding of transient responses of healthy cartilage to repetitive, exercise-induced loading and establish preliminary recommendations for future definitive studies of cartilage response to running. This article is protected by copyright. All rights reserved.

AIM To compare and assess T1rho values of the femorotibial cartilage compartments and subregional menisci in patients with hyperuricaemia at 3 T. MATERIALS AND METHODS Thirty-two patients were enrolled in the study and were subdivided into two subgroups: 15 healthy controls (three women, 12 men; mean age = 45.3 ± 10.9 years, age range 25–72 years) and 17 patients with asymptomatic hyperuricaemia (two women, 15 men; mean age = 44.4 ± 12.7 years, age range 26–77 years). All patients were evaluated using 3 T magnetic resonance imaging (MRI) using an eight-channel phased-array knee coil (transmit–receive). Wilcoxon's rank sum test and analysis of covariance (ANCOVA) were conducted to determine whether there were any statistically significant differences in the T1rho values of the femorotibial cartilage compartments and subregional menisci between the two subgroups. RESULTS Lateral tibial cartilage (45.8 ± 2.9 ms) in the healthy subgroup had significantly lower (p

Background We developed a fully automatic three-dimensional knee MRI analysis software that can quantify meniscus extrusion and cartilage measurements, including the projected cartilage area ratio (PCAR), which represents the ratio of the subject’s actual cartilage area to their ideal cartilage area. We also collected 3D MRI knee data from 561 volunteers (aged 30–79 years) from the “Kanagawa Knee Study.” Our purposes were to verify the accuracy of the software for automatic cartilage and meniscus segmentation using knee MRI and to examine the relationship between medial meniscus extrusion measurements and cartilage measurements from Kanagawa Knee Study data. Methods We constructed a neural network for the software by randomly choosing 10 healthy volunteers and 103 patients with knee pain. We validated the algorithm by randomly selecting 108 of these 113 subjects for training, and determined Dice similarity coefficients from five other subjects. We constructed a neural network using all data (113 subjects) for training. Cartilage thickness, cartilage volume, and PCAR in the medial femoral, lateral femoral, medial tibial, and lateral tibial regions were quantified by using the trained software on Kanagawa Knee Study data and their relationship with subject height was investigated. We also quantified the medial meniscus coverage ratio (MMCR), defined as the ratio of the overlapping area between the medial meniscus area and the medial tibial cartilage area to the medial tibial cartilage area. Finally, we examined the relationship between MMCR and PCAR at middle central medial tibial (mcMT) subregion located in the center of nine subregions in the medial tibial cartilage. Results Dice similarity coefficients for cartilage and meniscus were both approximately 0.9. The femoral and tibial cartilage thickness and volume at each region correlated with height, but PCAR did not correlate with height in most settings. PCAR at the mcMT was significantly correlated with MMCR. Conclusions Our software showed high segmentation accuracy for the knee cartilage and meniscus. PCAR was more useful than cartilage thickness or volume since it was less affected by height. Relations ips were observed between the medial tibial cartilage measurements and the medial meniscus extrusion measurements in our cross-sectional study. Trial registration UMIN, UMIN000032826; 1 September 2018

Background:There are currently limited human in vivo data characterizing the role of the meniscus in load distribution within the tibiofemoral joint.Purpose/Hypothesis:The purpose was to compare the strains experienced in regions of articular cartilage covered by the meniscus to regions of cartilage not covered by the meniscus. It was hypothesized that in response to walking, tibial cartilage covered by the meniscus would experience lower strains than uncovered tibial cartilage.Study Design:Descriptive laboratory study.Methods:Magnetic resonance imaging (MRI) of the knees of 8 healthy volunteers was performed before and after walking on a treadmill. Using MRI-generated 3-dimensional models of the tibia, cartilage, and menisci, cartilage thickness was measured in 4 different regions based on meniscal coverage and compartment: covered medial, uncovered medial, covered lateral, and uncovered lateral. Strain was defined as the normalized change in cartilage thickness before and after activity.Results:Within each compartment, covered cartilage before activity was significantly thinner than uncovered cartilage before activity ( P < .001). After 20 minutes of walking, all 4 regions experienced significant cartilage thickness decreases ( P < .01). The covered medial region experienced significantly less strain than the uncovered medial region ( P = .04). No difference in strain was detected between the covered and uncovered regions in the lateral compartment ( P = .40).Conclusion:In response to walking, cartilage that is covered by the meniscus experiences lower strains than uncovered cartilage in the medial compartment. These findings provide important baseline information on the relationship between in vivo tibial compressive strain responses and meniscal coverage, which is critical to understanding normal meniscal function.

This study aimed to determine the extent to which changes over 2.5 years in medial knee cartilage thickness and volume were predicted by: (1) Peak values of the knee adduction (KAM) and flexion moments; and (2) KAM impulse and loading frequency, representing cumulative load, after controlling for age, sex and body mass index (BMI). Adults with clinical knee osteoarthritis participated. At baseline and approximately 2.5 years follow-up, cartilage thickness and volume of the medial tibia and femur were segmented from magnetic resonance imaging scans. Gait kinematics and kinetics, and daily knee loading frequency were also collected at baseline. Multiple linear regressions predicted changes in cartilage morphology from baseline gait mechanics. Data were collected from 52 participants (41 women) [age 61.0 (6.9) y; BMI 28.5 (5.7) kg/m2 ] over 2.56 (0.51) years. There were significant KAM peak-by-BMI (p = 0.023) and KAM impulse-by-BMI (p = 0.034) interactions, which revealed that larger joint loads in those with higher BMIs were associated with greater loss of medial tibial cartilage volume. In conclusion, with adjustments for age, sex, and cartilage measurement at baseline, large magnitude KAM peak and KAM impulse each interacted with BMI to predict loss of cartilage volume of the medial tibia over 2.5 years among individuals with knee osteoarthritis. These data suggest that, in clinical knee osteoarthritis, exposure to large KAMs may be detrimental to cartilage in those with larger BMIs. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2476-2483, 2017.

Background Sprifermin is under investigation as a potential disease-modifying osteoarthritis drug (DMOAD). 2-yr results from the FORWARD study showed significant dose-dependent modification of cartilage thickness in the total femorotibial joint (TFTJ), medial and lateral femorotibial joints (MFTC, LFTC), and central medial and lateral TFTJ subregions, by quantitative (q)MRI.1 Objectives To determine whether qMRI findings from FORWARD (manual segmentation) could be reproduced in the same cartilage regions using an independent method (automated segmentation), on the same dataset/time period. Methods Pts were randomized 1:1:1:1:1 to: sprifermin 100 μg q6mo; 100 μg q12mo; 30 μg q6mo; 30 μg q12mo; and placebo (n=110/110/111/110/108).1 Cartilage thickness was assessed at baseline and 6, 12, 18, and 24 months using 1.5- or 3-Tesla MRI images, analyzed manually.1 The same images were analyzed by automated cartilage segmentation using active appearance models, a supervised machine learning method, to produce maps of cartilage thickness for weight-bearing femoral and tibial cartilage surfaces, subdivided into anatomical masks. Results were blinded for treatment and timepoint for both methods. No statistical comparisons between methods were conducted. Endpoints were change from baseline in: 1) cartilage thickness in the TFTJ, MFTC and LFTC, using regions duplicated based on published data;1 2) cartilage thickness in the central subregion of the medial and lateral tibia and femur (cMT, cMF, cLT, cLF [conventions used by the automated analysis investigators]). As in previous analyses, treatment effect was assessed by observed changes and adjusted using repeated ANCOVA on change from baseline, including treatment group, timepoint, and country as fixed factors, baseline value as covariate and treatment by timepoint as interaction. Results Based on automated segmentation, statistically significant, dose-dependent structural modification of cartilage thickness was observed over 2 yrs with sprifermin vs placebo for the TFTJ (overall treatment effect and dose response across all doses, both P Conclusion Cartilage thickness assessed by automated segmentation provided a consistent pattern of structural modification in FORWARD compared with manual segmentation. This is the first time that two independent methods of image analysis have reached the same conclusions in an interventional DMOAD trial. The findings strengthen the conclusions that sprifermin modifies cartilage loss/structural progression in knee OA. References [1] Hochberg, et al. ACR 2017 Disclosure of Interests Alan Brett Employee of: Employee of Imorphics, Manchester, UK, Michael A Bowes Employee of: Employee of Imorphics, Manchester, UK, Philip G Conaghan Consultant for: Flexion Therapeutics, AbbVie, Medivir, Merck Serono, Novartis, GlaxoSmithKline, Christoph Ladel Employee of: Employee of Merck KGaA, Darmstadt, Germany, Jeffrey Kraines Employee of: Employee of EMD Serono (a business of Merck KGaA, Darmstadt, Germany), Hans Guhring Employee of: Employee of Merck KGaA, Darmstadt, Germany, Flavie Moreau Employee of: Employee of EMD Serono (a business of Merck KGaA, Darmstadt, Germany), Felix Eckstein Shareholder of: Shareholder of Chondrometrics GmbH, Consultant for: Consulting fees from Merck KGaA, Samumed LLC, Abbvie, Bioclinica, TissueGene, Servier, and Roche, Employee of: Employee of Chondrometrics GmbH

BACKGROUND Medical imaging has become an invaluable tool to diagnose damage to cartilage. Depletion of glycosaminoglycans (GAG) has been shown to be one of the early signs of cartilage degradation. In order to investigate the topographical changes in GAG concentration caused by the anterior cruciate ligament transection (ACLT) surgery in a canine model, microscopic magnetic resonance imaging (µMRI) and microscopic computed tomography (µCT) were used to measure the GAG concentration with correlation from a biochemical assay, inductively coupled plasma optical emission spectroscopy (ICP-OES), to understand where the topographical and depth-dependent changes in the GAG concentration occur. METHODS This study used eight knee joints from four canines, which were examined 3 weeks after ACLT surgery. From right (n=3) and left (n=1) medial tibias of the ACLT and the contralateral side, two ex vivo specimens from each of four locations (interior, central, exterior and posterior) were imaged before and after equilibration in contrast agents. The cartilage blocks imaged using µMRI were approximately 3 mm × 5 mm and were imaged before and after eight hours submersion in a gadolinium (Gd) contrast agent with an in-plane pixel resolution of 17.6 µm2 and an image slice thickness of 1 mm. The cartilage blocks imaged using µCT were approximately 2 mm × 1 mm and were imaged before and after 24 hours submersed in ioxaglate with an isotropic voxel resolution of 13.4 µm3. ICP-OES was used to quantify the bulk GAG at each topographical location. RESULTS The pre-contrast µMRI and µCT results did not demonstrate significant differences in GAG between the ACLT and contralateral cartilage at all topographical locations. The post-contrast µMRI and µCT results demonstrated topographically similar significant differences in GAG concentrations between the ACLT and contralateral tibia. Using µMRI, the GAG concentrations (mg/mL) were measured for the ACLT and contralateral respectively, the exterior (54.0±3.6; 70.4±4.3; P=0.001) and interior (54.9±5.9; 71.0±5.9; P=0.029) demonstrated significant differences, but not for the central (61.0±12.0; 67.4±7.2; P=0.438) or posterior (61.6±6.3; 70.3±4.4; P=0.097) locations. Using µCT, the GAG concentrations (mg/mL) were measured for the ACLT and contralateral respectively, the exterior (68.8±0.4; 87.7±4.1; P=0.023) and interior (60.5±9.1; 82.6±8.7; P=0.039) demonstrated significant differences, but not for the central (53.5±5.5; 59.1±25.6; P=0.684) or posterior (52.3±6.2; 61.5±12.7; P=0.325) locations. The depth-dependent GAG (mg/mL) profiles showed significant differences in µMRI for the transitional zone (TZ) [exterior (28.1±4.7; 47.0±8.6; P=0.01) and interior (32.6±4.8; 43.8±8.7; P=0.025)], radial zone (RZ) 1 [exterior (49.6±4.8; 71.5±5.8; P=0.001) and interior (49.4±7.4; 66.7±6.8; P=0.041)], and RZ 2 [exterior (74.9±4.7; 91.8±2.9; P=0.001) and interior (77.1±6.0; 94.8±4.5; P=0.015)], and in µCT for the superficial zone (SZ) [interior (20.6±1.2; 40.4±5.4; P=0.004)], TZ [exterior (45.6±12.0; 61.8±0.5; P=0.049) and interior (36.3±11.7; 60.8±2.0; P=0.019)], and RZ 1 [exterior (61.1±4.1; 85.3±5.6; P=0.039) and interior (53.9±4.9; 78.0±5.1; P=0.041)] for the ACLT and contralateral, respectively. ICP-OES measured significant differences in GAG were found for the exterior (42.1±19.6; 65.3±16.2; P=0.017), central (43.4±4.4; 65.3±10.6; P=0.0111), and interior (46.8±5.6; 61.7±7.3; P=0.0445) but not for the posterior (52.6±12.1; 59.0±2.6; P=0.9252) medial tibia locations compared for the ACLT and contralateral, respectively. CONCLUSIONS The detection and correlation between the three techniques show a topographic depth-dependency on the initial GAG loss in injured cartilage. This topographic and high resolution investigation of ACLT cartilage demonstrated the potential of using µMRI and µCT to study and help diagnose cartilage with very early stages of osteoarthritis.

Background:Obesity, which potentially increases loading at the knee, is a common and modifiable risk factor for the development of knee osteoarthritis. The menisci play an important role in distributing joint loads to the underlying cartilage. However, the influence of obesity on the role of the menisci in cartilage load distribution in vivo is currently unknown.PurposeTo measure tibial cartilage thickness and compressive strain in response to walking in areas covered and uncovered by the menisci in participants with normal body mass index (BMI) and participants with high BMI.Study Design:Controlled laboratory study.Methods:Magnetic resonance (MR) images of the right knees of participants with normal BMI (2; n = 8) and participants with high BMI (>30 kg/m2; n = 7) were obtained before and after treadmill walking. The outer margins of the tibia, the medial and lateral cartilage surfaces, and the meniscal footprints were segmented on each MR image to create 3-dimensional models of the joint. Cartilage thickness was measured before and after walking in areas covered and uncovered by the menisci. Cartilage compressive strain was then determined from changes in thickness resulting from the walking task.Results:Before exercise, medial and lateral uncovered cartilage of the tibial plateau was significantly thicker than covered cartilage in both BMI groups. In the uncovered region of the lateral tibial plateau, participants with high BMI had thinner preexercise cartilage than those with a normal BMI. Cartilage compressive strain was significantly greater in medial and lateral cartilage in participants with high BMI compared with those with normal BMI in both the regions covered and those uncovered by the menisci.Conclusion:Participants with high BMI experienced greater cartilage strain in response to walking than participants with normal BMI in both covered and uncovered regions of cartilage, which may indicate that the load-distributing function of the meniscus is not sufficient to moderate the effects of obesity.Clinical Relevance:These findings demonstrate the critical effect of obesity on cartilage function and thickness in regions covered and uncovered by the menisci.

This paper aimed to evaluate the biomechanical effects of tibial bearing materials, from ultra-high-molecular-weight polyethylene (UHMWPE) to poly-ether-ether-ketone (PEEK) and carbon-fiber-reinforced poly-ether-ether-ketone (CFR-PEEK). The studies were conducted based on a validated finite element model. The geometry of the intact knee model was developed from computed tomography and magnetic resonance imaging of the left knee joint of a 37-year-old healthy male volunteer. Three different loading conditions, related to the loads applied in the experimental research, were applied to this study for model predictions and validation. The contact stress in the other compartments was under normal walking conditions. Also, stresses on five regions of the tibia bone were analyzed under normal walking conditions. The lowest contact stress between the lateral meniscus and tibial cartilage was achieved in the order of the use of CFR-PEEK, PEEK, and UHMWPE tibial bearings. Moreover, CFR-PEEK and PEEK tibial bearings indicated lower and greater stresses on cortical and trabecular bones, respectively, compared to the UHMWPE tibial bearing. These results show that CFR-PEEK can be used as a tibial bearing material as an alternative to UHMWPE, and such a change in the material may be a good method for reducing potential anteromedial pain.

Tibial plateau defects present a challenging clinical entity, as their location, geometry, and proximity to surrounding structures make them technically challenging to treat. Additionally, the literature on the management of tibial plateau cartilage defects is not well-developed. Techniques such as osteochondral allografts or autografts are technically complicated in these regions and should be approached with caution. Microfracture is a well-established technique that is technically simple and has low rates of complications, and it is well-suited for treating tibial plateau defects. However, concerns about the long-term outcomes of microfracture have been raised, likely secondary to the generation of fibrocartilage. Newer treatments that are available including BioCartilage (Arthrex, Naples, FL) and matrix-associated autologous chondrocyte implantation (MACI) may have promise in this technically demanding area.

Introduction Discoid meniscus is a well-documented knee pathology, and there are many cases of medial or lateral discoid meniscus reported in the literature. However, ipsilateral concurrent medial and lateral discoid meniscus is very rare, and only a few cases have been reported. Herein, we report a case of concurrent medial and lateral discoid meniscus. Case report A 27-year-old Japanese man complained of pain on medial joint space in his right knee that was diagnosed as a complete medial and lateral discoid meniscus. In magnetic resonance imaging, although the lateral discoid meniscus had no tear, the medial discoid meniscus had a horizontal tear. Arthroscopic examination of his right knee similarly revealed that the medial discoid meniscus had a horizontal tear. In addition, the discoid medial meniscus also had an anomalous insertion to the anterior cruciate ligament, and there was also mild fibrillation of the medial tibial cartilage surface. We performed arthroscopic partial meniscectomy for the torn medial discoid meniscus but not for the asymptomatic lateral discoid meniscus. The latest follow-up at 18 months indicated satisfactory results. Conclusion We report a rare case of ipsilateral medial and lateral discoid meniscus with medial meniscus tear. The medial discoid meniscus with tear was treated with partial meniscectomy, whereas the lateral discoid meniscus without tear was only followed up.

BACKGROUND Knee osteoarthritis (OA) is suggested to be induced by multi-factors, and mechanical environment is regarded as a risky factor. OBJECTIVE To investigate the effect of isolated mechanical factor on cartilage. METHODS An active wear test system was designed to perform parameters-controlled in vitro wear tests on rat knee joints with specific load magnitude, flexion-extension angle, and movement frequency. Six hind limbs of 9-month-old male Sprague-Dawley rats, with an additional spring on the medial side, were worn by using the custom-designed apparatus. Researchers observed both the menisci and tibial cartilages of these hind limbs using multiphoton laser scanning microscopy to analyze the change of the collagen microstructure caused by wear. RESULTS Collagen microstructure of both the medial and lateral meniscus became disordered under cyclic load. Some tissues on the surface of the medial tibial cartilage were removed and the middle layer of the medial compartment displayed cracks. On the contrary, the lateral tibial cartilage was intact. CONCLUSIONS The results implied that cyclic load caused menisci microstructure disarrangement prior to tibial cartilage damage and the collagen structure of mid-layer tibial cartilage failed before that of the superficial layer under the kinematics adopted in the study.

The aim of this study was to determine if the fast bowling action in cricket, during which the front leg experiences about twice the loading of the back leg, causes a clinically significant difference in the normalized medial or lateral tibial cartilage volume of the higher loaded front versus the back leg.

Background It is still debated whether strenuous running in the inflammatory phase produces beneficial or harmful effect in rat knees. We examined (1) the dropout rate of rats during a 30-km running protocol, (2) influences of strenuous running and/or low amounts of mono-iodoacetate injection on cartilage, and (3) the effect of strenuous running on synovitis. Methods Rats were forced to run 30 km over 6 weeks and the dropout rate was examined. One week after 0.1 mg mono-iodoacetate was injected into the right knee, rats were forced to run either 15 km or not run at all over 3 weeks, after which knee cartilage was evaluated. Synovium at the infrapatellar fat pad was also examined histologically. Results Even though all 12 rats run up to 15 km, only 6 rats completed 30 km of running. Macroscopically, 0.1 mg mono-iodoacetate induced erosion at the tibial cartilage irrespective of 15 km of running. Histologically, 0.1 mg mono-iodoacetate induced loss of cartilage matrix in the tibial cartilage, and an additional 15 km of strenuous running significantly exacerbated the loss. Synovitis caused by mono-iodoacetate improved after running. Conclusions Only 50% of rats completed 30 km of running because of foot problems. Strenuous running further exacerbated tibial cartilage erosion but did not influence synovitis induced by mono-iodoacetate.

Objective To assess the multirater agreement of the modified Outerbridge system for the grading of predefined areas of femorotibial cartilage at CT arthrography with multiple readers, with varying experience. Design Five readers with varying experience (two junior radiologists, three musculoskeletal radiologists including two experts in cartilage imaging) separately analyzed 962 cartilage sectors from pre-divided knee CT arthrograms with femorotibial osteoarthritis (Kellgren/Lawrence = 3). Each cartilage area was graded twice by each reader, at a three-month interval, according to the modified 5-grade Outerbridge system. Interobserver and intraobserver agreement were assessed. After the second reading, 121 areas exhibiting the highest interobserver disagreement were reviewed in consensus to determine the sources of disagreement. Results The global interobserver agreement was fair (k = 0.35), and increased with the grade (from k = 0.14 to k = 0.76 from grade 0–4). The intraobserver agreement varied with the readers’ experience from moderate (k = 0.59) to almost perfect (k = 0.92). The majority of cases of disagreement (44%) was due to difficulties in assessing the normal variations of cartilage thickness, including diffuse cartilage thinning (23%) and normal variants of cartilage thickness (22%). 32% of cases of disagreement were due to retrospectively avoidable interpretation errors. Conclusions The multirater agreement of the modified Outerbridge system is only fair when readers of different level of experience are taken into account, and interobserver agreement increases with readers’ experience. However, interobserver agreement is substantial for grade 4 lesions. We report normal variations of cartilage thickness that may improve observer agreement in reporting cartilage lesions.

Anterior cruciate ligament (ACL) disruption is a common injury that is detrimental to an athlete's quality of life. Determining the mechanisms that cause ACL injury is important in order to develop proper interventions. A failure locus defined as various combinations of loadings and movements, internal/external rotation of femur and valgus and varus moments at a 25(o) knee flexion angle leading to ACL failure was obtained. The results indicated that varus and valgus movements were more dominant to the ACL injury than femoral rotation. Also, Von Mises stress in the lateral tibial cartilage during the valgus ACL injury mechanism was 83% greater than that of the medial cartilage during the varus mechanism of ACL injury. The results of this study could be used to develop training programmes focused on the avoidance of the described combination of movements which may lead to ACL injury.

Purpose To validate the accuracy of T1 measurement by three-dimensional Look-Locker method (3D LL) for delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) of human subjects with and without osteoarthritis (OA), as compared with two-dimensional inversion recovery fast spin-echo (2D IR-FSE) technique. Materials and Methods MR sagittal images of the knees were acquired for T1 mapping in 29 subjects with standard 2D IR-FSE and 3D LL sequences 90–135 min following administration of 0.2 mmol/kg Gd-DTPA2−. T1 maps of femoral and tibial cartilage were generated using custom software. Comparisons in T1 values between the two techniques were performed using regression analysis. Results Good agreement in T1 values between 2D IR-FSE and 3D LL was observed (R values of 0.90, and 0.85, and 0.86 for all, OA, and control subjects, respectively) when acquired within 15 min. Conclusion The 3D LL sequence provides accurate T1 estimates of articular cartilage with advantages of entire joint coverage, shorter acquisition time, and a wide range of inversion times sampled within a single acquisition. J. Magn. Reson. Imaging 2008. © 2008 Wiley-Liss, Inc.

Abstract The orientation and organisation of collagen fibrils play an important role in the mechanical functioning of the articular cartilage (AC) that covers the surfaces in the diarthrodial joints. In the adult animal, typically an arcade like 'Benninghoff structure' is found. Because the remodelling capacity of the collagen network in the adult animal is limited, this Benninghoff structure needs to develop before the animal reaches maturity, and it needs to develop correctly. The aim of this study is to use quantitative polarised light microscopy (qPLM) and scanning electron microscopy (SEM) techniques to investigate if this Benninghoff structure is already present in the young animal, and to quantitatively investigate possible differences in collagen structure in the equine distal metacarpus of the young and adult animal. In total, 21 forelimbs of 13 horses are used. In animals of age 10 months and older, we find an arcade like Benninghoff structure for the collagen fibril network in both the qPLM and SEM study. The qPLM study shows that the collagen's predominant orientation is parallel to the articular surface throughout the entire cartilage depth in two animals directly after birth. These findings are supported by SEM results on a foal. We conclude that structural remodelling of the collagen network in AC occurs in the first months after birth. Because animals start with collagen parallel to the articular surface and need to remodel this structure to a Benninghoff architecture, and because collagen structure is an important parameter for AC mechanics and mechanobiology, these results suggest implications for AC epigenetics.

The topographical distributions of the zonal properties of articular cartilage over the medial tibia from an experimental osteoarthritis (OA) model were evaluated as the function of external loading by microscopic Magnetic Resonance Imaging (μMRI). T2 relaxation times and cartilage thicknesses were measured at 17.6μm resolution from 118 specimens, which came from thirteen dogs (six 8-week and seven 12-week after surgery), with and without mechanical loading. In addition, bulk mechanical modulus was measured topographically from each tibia surface. The total thickness decreased significantly under the external loading, in which the relative thickness of the superficial zone (SZ) and the transitional zone (TZ) increased whereas the radial zones (RZs) decreased. In the bulk data, T2(55°) decreased significantly (p0.05) at 8-week. Complex relationships were found in the zonal tissue properties as a function of external loading with the progress of OA. T2 in the superficial zone changed more profoundly than the same properties in the radial zone as the function of external loading at all OA time-points. This study confirms that the OA affects the load-induced changes in the molecular distribution and structure of cartilage, which are both depth-dependent and topographically distributed. Such detailed knowledge of mechanobiological changes in specific tibial cartilage zones and locations with OA progress could improve the early detection of the subtle softening of cartilage that accompany pre-clinical stages of OA.

PURPOSE To evaluate the influence of Gd-DTPA on cartilage T2 mapping using turbo-mixed (tMIX) imaging, and to show the possible usefulness of the tMIX technique for simultaneously acquiring T1 and T2 information in cartilage. MATERIALS AND METHODS Twenty volunteers underwent MRI of the knee using the tMIX sequence before and after gadolinium administration. T1 and T2 maps were calculated. The mean T1 was determined on the pre- and postcontrast T1 maps. T2 relaxation values before and after gadolinium administration were statistically analyzed. RESULTS The obtained relaxation values are in correspondence with previously published data. The mean T1 before gadolinium administration was 449 msec +/- 34.2 msec (SD), and after gadolinium administration it was 357 msec +/- 55.8 msec (SD). The postcontrast T1 relaxation range was 221.5-572.8 msec. The mean T2 of the precontrast T2 maps was 34.2 msec +/- 3.1 msec (SD), and the mean T2 of the postcontrast T2 maps was 32.5 msec +/- 3.1 msec (SD). These are statistically significant different values. A correction for the postcontrast T2 values, using a back-calculation algorithm, yielded a 98% correlation with the precontrast T2 values. CONCLUSION The absolute difference of pre- and postcontrast T2 is very small and is ruled out using the back-calculation algorithm. Combined T1-T2 tMIX cartilage mapping is a valuable alternative for separate T1 and T2 cartilage mapping.

PURPOSE To demonstrate the in vivo feasibility of measuring spin-lattice relaxation time in the rotating frame (T(1rho)); and T(1rho)-dispersion in human femoral cartilage. Furthermore, we aimed to compute the baseline T(1rho)-relaxation times and spin-lock contrast (SLC) maps on healthy volunteers, and compare relaxation times and signal-to-noise ratio (SNR) with corresponding T(2)-weighted images. MATERIALS AND METHODS All MR imaging experiments were performed on a 1.5 T GE Signa scanner (GEMS, Milwaukee, WI) using a custom built 15-cm transmit-receive quadrature birdcage radio-frequency (RF) coil. The T(1rho)-prepared magnetization was imaged with a single-slice two-dimensional fast spin-echo (FSE) pulse sequence preencoded with a three-pulse cluster consisting of two hard 90 degrees pulses and a low power spin-lock pulse. T(1rho)-dispersion imaging was performed by varying the spin-lock frequency from 100 to 500 Hz in five steps in addition to varying the length of the spin-lock pulse. RESULTS The average T(1rho)-relaxation times in the weight-bearing (WB) and nonweight-bearing (NWB) regions of the femoral condyle were 42.2 +/- 3.6 msec and 55.7 +/- 2.3 msec (mean +/- SD, N = 5, P < 0.0001), respectively. In the same regions, the corresponding T(2)-relaxation times were 31.8 +/- 1.5 msec and 37.6 +/- 3.6 msec (mean +/- SD, N = 5, P < 0.0099). T(1rho)-weighted images have approximately 20%-30% higher SNR than the corresponding T(2)-weighted images for similar echo time. The average SLC in the WB region of femoral cartilage was 30 +/-4.0%. Furthermore, SLC maps provide better contrast between fluid and articular surface of femoral-tibial joint than T(1rho)-maps. The T(1rho)-relaxation times varied from 32 msec to 42 msec ( approximately 31%) in the WB and 37 msec to 56 msec ( approximately 51%) in NWB regions of femoral condyle, respectively, in the frequency range 0-500 Hz (T(1rho)-dispersion). CONCLUSION The feasibility of performing in vivo T(1rho) relaxation mapping in femoral cartilage at 1.5T clinical scanner without exceeding Food and Drug Administration (FDA) limits on specific absorption rate (SAR) of RF energy was demonstrated.

The aim of this study was to analyze the precision of tibial cartilage morphometry, by using a fast, coronal water-excitation sequence with high spatial resolution, to compare the reproducibility of 3D thickness vs volume estimates, and to test the technique in patients with severe osteoarthritis. The tibiae of 8 healthy volunteers and 3 patients selected for total knee arthroplasty were imaged repeatedly with a water-excitation sequence (image time 6 h 19 min, resolution 1.2 x 0.31 x 0.31 mm(3)), with the knee being repositioned between each replicate acquisition. After 3D reconstruction, the cartilage volume, the mean, and the maximal tibial cartilage thickness were determined by 3D Euclidean distance transformation. In the volunteers, the precision of the volume measurements was 2.3 % (CV%) in the medial and 2.6 % in the lateral tibia. The reproducibility of the mean cartilage thickness was similar (2.6 and 2.5 %, respectively), and that of the maximal thickness lower (6.5 and 4.4 %). The patients showed a considerable reduction in volume and thickness, the precision being comparable with that in the volunteers. We find that, using a new imaging protocol and computational algorithm, it is possible to determine tibial cartilage morphometry with high precision in healthy individuals as well as in patients with osteoarthritis.

To analyze the interrelationships between the structure, composition, and mechanical properties of articular cartilage, canine knee (n = 10) femoral and tibial cartilages were used as experimental tissues. The biomechanical properties, instant shear modulus (IM), and equilibrium shear modulus (EM) of articular cartilage were investigated using an in situ indentation creep technique. The local variations in the concentration of glycosaminoglycans (GAGs) in the cartilage were measured with a microspectrophotometer after safranin-O staining of histological sections. Using a computer-based quantitative polarized light microscopy method, area-specific measurements of the optical path difference were performed to quantitate collagen-related optical retardation (Γ) of cartilage zones. The IM and EM were 131.3 and 51.2% higher (p < 0.001) in the femoral cartilage than in the tibial cartilage, respectively. The mean thickness of the superficial zone and the relative proportion of the superficial zone from the total uncalcified cartilage was 107.1 and 155.3% higher (p < 0.001) at the femoral test points than in the tibial ones, respectively. The mean thickness of the tibial uncalcified cartilage was 21.1% higher (p < 0.001) than the thickness of the femoral cartilage. The GAG concentration of the tibial cartilage was higher (14.8%, p < 0.001) than that of the femoral cartilage, especially in the superficial zone (50.0%, p < 0.05), whereas the Γ of the collagen network in the superficial zone of the femoral cartilage was 64.7% higher (p < 0.001) than in the tibial cartilage. The percent relative thickness and retardation Γ of the superficial zone correlated positively with the indentation stiffness of the canine knee articular cartilage. These observations indicate that cartilage is structurally inhomogenous and layered tissue and the local organization of collagen and GAG concentration of the articular cartilage regulate the biomechanical properties of the tissue. The structure and composition of the superficial articular cartilage significantly affects the indentation response of the canine knee articular cartilage. © 1999 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 48: 99–107, 1999

Our comparative study of the knees of horses and cows (paraphrased as highly evolved joggers and as domesticated couch-potatoes, respectively) demonstrates significant differences in the posterior sections of bovine and equine tibial cartilage, which are consistent with specialisation for gait. These insights were possible using a novel analytical measuring technique based on the shearing of small biopsy samples, called dynamic shear analysis. We assert that this technique could provide a powerful new tool to precisely quantify the pathology of osteoarthritis for the medical field.

OZKAN, Arif/0000-0002-1288-6166; Atmaca, Halil/0000-0001-5820-6456 WOS: 000327084800004 PubMed: 23192762 Depending on the location and extent of the meniscectomy, loading on the tibial articular cartilage alters. The main purpose of the present study was to analyze the loading on the tibial articular cartilage following medial meniscectomy performed in various location and extent, as well as in the healthy knee, via finite element analyses on the solid models. Totally, 11 finite element solid models, including the reference model, were created to investigate the effect of location (anterior, posterior, longitudinal) and extent of meniscectomy (25, 50, 75, and 100 %) on loading of tibial articular cartilage. Maximum equivalent stress of the tibial cartilage was measured 0.86 Megapascal in the reference model and increased approximately by 78 % in 25 % meniscectomy group, 177.9 % in 50 %, 473.8 % in 75 % meniscectomy group, and 752.6 % in total meniscectomy. When only the amount of meniscal tissue removed was considered ignoring the location of meniscectomy, no significant difference was found in the amount of tissue excised between 25 % meniscectomy and 50 % meniscectomy, as well as between 75 % meniscectomy and total meniscectomy. In all meniscectomy models, the loadings on tibial articular cartilage increased. Except total meniscectomy, the highest impact was observed in longitudinal 75 % meniscectomy. During the surgical treatment, the contributions of menisci on load absorption by increasing the tibiofemoral contact area must be considered. In fact, the increase in the rate of loading on tibial articular cartilage depends on according to type and amount of meniscectomy.

Osteoarthritis (OA) is the most common form of joint disease and often characterized by cartilage changes. Accurate quantitative methods are needed to rapidly screen large image databases to assess changes in cartilage morphology. We therefore propose a new automatic atlas-based cartilage segmentation method for future automatic OA studies. Atlas-based segmentation methods have been demonstrated to be robust and accurate in brain imaging and therefore also hold high promise to allow for reliable and high-quality segmentations of cartilage. Nevertheless, atlas-based methods have not been well explored for cartilage segmentation. A particular challenge is the thinness of cartilage, its relatively small volume in comparison to surrounding tissue and the difficulty to locate cartilage interfaces – for example the interface between femoral and tibial cartilage. This paper focuses on the segmentation of femoral and tibial cartilage, proposing a multi-atlas segmentation strategy with non-local patch-based label fusion which can robustly identify candidate regions of cartilage. This method is combined with a novel three-label segmentation method which guarantees the spatial separation of femoral and tibial cartilage, and ensures spatial regularity while preserving the thin cartilage shape through anisotropic regularization. Our segmentation energy is convex and therefore guarantees globally optimal solutions. We perform an extensive validation of the proposed method on 706 images of the Pfizer Longitudinal Study. Our validation includes comparisons of different atlas segmentation strategies, different local classifiers, and different types of regularizers. To compare to other cartilage segmentation approaches we validate based on the 50 images of the SKI10 dataset.

Nearly 3% of individuals worldwide experience pain, immobility, and compromised quality of life due to knee osteoarthritis (OA)1. It has been widely accepted that joint mechanics play a critical role in the initiation and progression of knee OA2. A shift away from the normal joint motion, for example due to injury or malalignment, is believed to produce an abnormal pattern of cartilage loading that creates unusual and damaging stresses within the tissue. Accurate knowledge of cartilage’s normal mechanical response to physiological loading—and particularly the regional dependence of this response—is critical to successfully testing this theory. To our knowledge, little is known about the regionally-dependent mechanical response of healthy human tibial cartilage under physiological loading conditions. There is also a compelling need for more accurate cartilage data to be integrated into computational simulations of the knee joint. Hence, the purpose of this study was two-fold: 1) to characterize the typical stress-strain response of tibial cartilage at 21 locations across the tibial plateau when subjected to loading representative of human walking, and 2) to demonstrate that these 21 sites can be reduced to a small number of regions displaying significantly different average moduli.

Medial tibial cartilage volume (mm) Peak KRM (Nm/BW*HT%) -0.21 (-0.49 to 0.07) 0.145 -0.20 (-0.48 to 0.09) 0.178 KRM angular impulse (Nm.s/BW*HT%) -0.92 (-1.8 to -0.03) 0.042 -1.05 (-1.98 to -0.12) 0.027 Lateral tibial cartilage volume (mm) Peak KRM (Nm/BW*HT%) -0.99 (-1.83 to -0.17) 0.019 -1.07 (-1.89 to -0.24) 0.012 KRM angular impulse (Nm.s/BW*HT%) -2.53 (-5.18 to 0.11) 0.060 -3.18 (-6.11 to -0.76) 0.012 Total tibial cartilage volume (mm) Peak KRM (Nm/BW*HT%) -0.34 (-0.59 to -0.08) 0.010 -0.35 (-0.60 to -0.09) 0.008 KRM angular impulse (Nm.s/BW*HT%) -1.02 (-1.83 to -0.21) 0.014 -1.29 (-2.11 to -0.47) 0.002

The effects of meniscectomy and anterior cruciate ligament transection on knee joint compression compliance, capacity of energy storage and cartilage gross morphology were studied in rabbits six and 12 weeks postoperatively. Joints with meniscectomy and intact ligaments at 12 weeks had a similar joint compression compliance as sham-operated joints with intact menisci, but had moderate unicompartmental osteoarthritis. Further, the capacity of energy storage of such a joint was reduced. Knees with anterior cruciate ligament transection had a higher joint compression compliance than knees with intact joint structures. Anterior cruciate ligament transection caused severe cartilage degeneration of both knee compartments at 6 weeks, but in knees with intact menisci the tibial cartilage was better preserved than in knees with meniscectomy. Synovitis was pronounced in anterior cruciate ligament transected knees. In conclusion, meniscectomy reduced the capacity of energy storage of the joint and was followed by moderate unicompartmental cartilage degeneration at 12 weeks. Anterior cruciate ligament transection especially when combined with meniscectomy led during a similar observation period to more dramatic effects on joint compression compliance and morphology.