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Integrating MR imaging with full-surface indentation mapping of femoral cartilage in an ex vivo porcine stifle
Abstract
The potential of MRI to predict cartilage mechanical properties across an entire cartilage surface in an ex vivo model would enable novel perspectives in modeling cartilage tolerance and predicting disease progression. The purpose of this study was to integrate MR imaging with full-surface indentation mapping to determine the relationship between femoral cartilage thickness and T2 relaxation change following loading, and cartilage mechanical properties in an ex vivo porcine stifle model. Matched-pairs of stifle joints from the same pig were randomized into either 1) an imaging protocol where stifles were imaged at baseline and after 35 min of static axial loading; and 2) full surface mapping of the instantaneous modulus (IM) and an electromechanical property named quantitative parameter (QP). The femur and femoral cartilage were segmented from baseline and post-intervention scans, then meshes were generated. Coordinate locations of the indentation mapping points were rigidly registered to the femur. Multiple linear regressions were performed at each voxel testing the relationship between cartilage outcomes (thickness change, T2 change) and mechanical properties (IM, QP) after accounting for covariates. Statistical Parametric Mapping was used to determine significance of clusters. No significant clusters were identified; however, this integrative method shows promise for future work in ex vivo modeling by identifying spatial relationships among variables.
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Objective
To evaluate the agreement, accuracy, and longitudinal reproducibility of quantitative cartilage morphometry from 2D U-Net-based automated segmentations for 3T coronal fast low angle shot (corFLASH) and sagittal double echo at steady-state (sagDESS) MRI.
Methods
2D U-Nets were trained using manual, quality-controlled femorotibial cartilage segmentations available for 92 Osteoarthritis Initiative healthy reference cohort participants from both corFLASH and sagDESS (n = 50/21/21 training/validation/test-set). Cartilage morphometry was computed from automated and manual segmentations for knees from the test-set. Agreement and accuracy were evaluated from baseline visits (dice similarity coefficient: DSC, correlation analysis, systematic offset). The longitudinal reproducibility was assessed from year-1 and -2 follow-up visits (root-mean-squared coefficient of variation, RMSCV%).
Results
Automated segmentations showed high agreement (DSC 0.89–0.92) and high correlations (r ≥ 0.92) with manual ground truth for both corFLASH and sagDESS and only small systematic offsets (≤ 10.1%). The automated measurements showed a similar test–retest reproducibility over 1 year (RMSCV% 1.0–4.5%) as manual measurements (RMSCV% 0.5–2.5%).
Discussion
The 2D U-Net-based automated segmentation method yielded high agreement compared with manual segmentation and also demonstrated high accuracy and longitudinal test–retest reproducibility for morphometric analysis of articular cartilage derived from it, using both corFLASH and sagDESS.
Osteoarthritis (OA) is a disease characterized by the degeneration of cartilage tissue, and is a leading cause of disability in the United States. The clinical diagnosis of OA includes the presence of pain and radiographic imaging findings, which typically do not present until advanced stages of the disease when treatment is difficult. Therefore, identifying new methods of OA detection that are sensitive to earlier pathological changes in cartilage, which may be addressed prior to the development of irreversible OA, is critical for improving OA treatment. A potentially promising avenue for developing early detection methods involves measuring the tissue’s in vivo mechanical response to loading, as changes in mechanical function are commonly observed in ex vivo studies of early OA. However, thus far the mechanical function of cartilage has not been widely assessed in vivo. Therefore, the purpose of this study was to develop a novel methodology that can be used to measure an in vivo mechanical property of cartilage: the characteristic recovery time. Specifically, in this study we quantified the characteristic recovery time of cartilage thickness after exercise in relatively young subjects with asymptomatic cartilage. Additionally, we measured baseline cartilage thickness and T1rho and T2 relaxation times (quantitative MRI) prior to exercise in these subjects to assess whether baseline MRI measures are predictive of the characteristic recovery time, to understand whether or not the characteristic recovery time provides independent information about cartilage’s mechanical state. Our results show that the mean recovery strain response across subjects was well-characterized by an exponential approach with a characteristic time of 25.2 min, similar to literature values of human characteristic times measured ex vivo. Further, we were unable to detect a statistically significant linear relationship between the characteristic recovery time and the baseline metrics measured here (T1rho relaxation time, T2 relaxation time, and cartilage thickness). This might suggest that the characteristic recovery time has the potential to provide additional information about the mechanical state of cartilage not captured by these baseline MRI metrics. Importantly, this study presents a noninvasive methodology for quantifying the characteristic recovery time, an in vivo mechanical property of cartilage. As mechanical response may be indicative of cartilage health, this study underscores the need for future studies investigating the characteristic recovery time and in vivo cartilage mechanical response at various stages of OA.
The diagnosis of osteoarthritis (OA) currently depends on the presence of pain and radiographic imaging findings, which generally do not present until later stages of the disease when the condition is difficult to treat. Therefore, earlier detection of OA pathology is needed for improved disease management. Ex vivo cartilage studies indicate that changes in the mechanical function of cartilage occur as degeneration progresses during OA. Thus, measurement of the in vivo cartilage mechanical response may serve as an earlier indicator of OA pathology. Though mechanical characterization is classically performed during loading, the unloading (recovery) response of cartilage may also enable determination of mechanical response. Therefore, the purpose of this study was to validate the use of the recovery response for mechanical characterization of cartilage in a controlled, ex vivo environment. To do so, confined compression creep and recovery tests were conducted on cartilage explants (N = 10), and the resulting mechanical properties from both the creep and recovery phases were compared. No statistically significant differences were found in the mechanical properties between the two phases, reinforcing the hypothesis that unloading (recovery) may be a good surrogate for loading.
Cartilage metabolism—both the synthesis and breakdown of cartilage constituents and architecture—is influenced by its mechanical loading. Therefore, physical activity is often recommended to maintain cartilage health and to treat or slow the progression of osteoarthritis, a debilitating joint disease causing cartilage degeneration. However, the appropriate exercise frequency, intensity, and duration cannot be prescribed because direct in vivo evaluation of cartilage following exercise has not yet been performed. To address this gap in knowledge, we developed a cartilage stress test to measure the in vivo strain response of healthy human subjects’ tibial cartilage to walking exercise. We varied both walk duration and speed in a dose-dependent manner to quantify how these variables affect cartilage strain. We found a nonlinear relationship between walk duration and in vivo compressive strain, with compressive strain initially increasing with increasing duration, then leveling off with longer durations. This work provides innovative measurements of cartilage creep behavior (which has been well-documented in vitro but not in vivo) during walking. This study showed that compressive strain increased with increasing walking speed for the speeds tested in this study (0.9–2.0 m/s). Furthermore, our data provide novel measurements of the in vivo strain response of tibial cartilage to various doses of walking as a mechanical stimulus, with maximal strains of 5.0% observed after 60 minutes of walking. These data describe physiological benchmarks for healthy articular cartilage behavior during walking and provide a much-needed baseline for studies investigating the effect of exercise on cartilage health.
Abstract Background Obesity is a primary risk factor for the development of knee osteoarthritis (OA). However, there remains a lack of in vivo data on the influence of obesity on knee cartilage mechanics and composition. The purpose of this study was to determine the relationship between obesity and tibiofemoral cartilage properties. Methods Magnetic resonance images (3T) of cartilage geometry (double-echo steady-state) and T1rho relaxation of the knee were obtained in healthy subjects with a normal (n = 8) or high (n = 7) body mass index (BMI) before and immediately after treadmill walking. Subjects had no history of lower limb injury or surgery. Bone and cartilage surfaces were segmented and three-dimensional models were created to measure cartilage thickness and strain. T1rho relaxation times were measured before exercise in both the tibial and femoral cartilage in order to characterize biochemical composition. Body fat composition was also measured. Results Subjects with a high BMI exhibited significantly increased tibiofemoral cartilage strain and T1rho relaxation times (P
The response to loading of human articular cartilage as assessed by magnetic resonance imaging (MRI) remains to be defined in relation to histology and biomechanics. Therefore, an MRI-compatible whole-knee joint loading device for the functional in situ assessment of cartilage was developed and validated in this study. A formalin-fixed human knee was scanned by computed tomography in its native configuration and digitally processed to create femoral and tibial bone models. The bone models were covered by artificial femoral and tibial articular cartilage layers in their native configuration using cartilage-mimicking polyvinyl siloxane. A standardized defect of 8 mm diameter was created within the artificial cartilage layer at the central medial femoral condyle, into which native cartilage samples of similar dimensions were placed. After describing its design and specifications, the comprehensive validation of the device was performed using a hydraulic force gauge and digital electronic pressure-sensitive sensors. Displacement-controlled quasi-static uniaxial loading to 2.5 mm \((\delta _{2.5})\) and 5.0 mm \((\delta _{5.0})\) of the mobile tibia versus the immobile femur resulted in forces of \(141 \pm 8\) N \((\delta _{2.5})\) and \(906 \pm 38\) N \((\delta _{5.0})\) (on the entire joint) and local pressures of \(0.680 \pm 0.088\) MPa \((\delta _{2.5})\) and \(1.050 \pm 0.100\) MPa \((\delta _{5.0})\) (at the site of the cartilage sample). Upon confirming the MRI compatibility of the set-up, the response to loading of macroscopically intact human articular cartilage samples (\(n=5\)) was assessed on a clinical 3.0-T MR imaging system using clinical standard proton-density turbo-spin echo sequences and T2-weighted multi-spin echo sequences. Serial imaging was performed at the unloaded state \((\delta _{0})\) and at consecutive loading positions (i.e. at \(\delta _{2.5}\) and \(\delta _{5.0})\). Biomechanical unconfined compression testing (Young’s modulus) and histological assessment (Mankin score) served as the standards of reference. All samples were histologically intact (Mankin score, \(1.8 \pm 1.3\)) and biomechanically reasonably homogeneous (Young’s modulus, \(0.42 \pm 0.14\) MPa). They could be visualized in their entirety by MRI and significant decreases in sample height [\(\delta _{0}\): \(2.86 \pm 0.25\) mm; \(\delta _{2.5}\): \(2.56 \pm 0.25\) mm; \(\delta _{5.0}\): \(2.02 \pm 0.16\) mm; \(p<0.001\) (repeated-measures ANOVA)] as well as pronounced T2 signal decay indicative of tissue pressurization were found as a function of compressive loading. In conclusion, our compression device has been validated for the noninvasive response-to-loading assessment of human articular cartilage by MRI in a close-to-physiological experimental setting. Thus, in a basic research context cartilage may be functionally evaluated beyond mere static analysis and in reference to histology and biomechanics.
Tissue material properties are crucial to understanding their mechanical function, both in healthy and diseased states. However, in certain circumstances logistical limitations can prevent testing on fresh samples necessitating one or more freeze-thaw cycles. To date, the nature and extent to which the material properties of articular cartilage are altered by repetitive freezing have not been explored. Therefore, the aim of this study is to quantify how articular cartilage mechanical properties, measured by nanoindentation, are affected by multiple freeze-thaw cycles. Canine cartilage plugs (n = 11) from medial and lateral femoral condyles were submerged in phosphate buffered saline, stored at 3 − 5°C and tested using nanoindentation within 12 hours. Samples were then frozen at −20°C and later thawed at 3 − 5 °C for 3 hours before material properties were re-tested and samples re-frozen under the same conditions. This process was repeated for all 11 samples over three freeze-thaw cycles. Overall mean and standard deviation of shear storage modulus decreased from 1.76 ± 0.78 to 1.21 ± 0.77 MPa (p = 0.91), shear loss modulus from 0.42 ± 0.19 to 0.39 ± 0.17 MPa (p=0.70) and elastic modulus from 5.13 ± 2.28 to 3.52 ± 2.24 MPa (p = 0.20) between fresh and three freeze-thaw cycles respectively. The loss factor increased from 0.31 ± 0.38 to 0.71 ± 1.40 (p = 0.18) between fresh and three freeze-thaw cycles. Inter-sample variability spanned as much as 10.47 MPa across freezing cycles and this high-level of biological variability across samples likely explains why overall mean “whole-joint” trends do not reach statistical significance across the storage conditions tested. As a result multiple freeze-thaw cycles cannot be explicitly or statistically linked to mechanical changes within the cartilage. However, the changes in material properties observed herein may be sufficient in magnitude to impact on a variety of clinical and scientific studies of cartilage, and should be considered when planning experimental protocols.
Inappropriate floors in pig pens and slippery floor conditions may cause leg problems that reduce animal welfare. Therefore the objectives of the present study were to characterise the walk of pigs on dry concrete solid floor, to evaluate whether pigs modify their gait according to floor condition, and to suggest a coefficient of friction (COF) that ensures safe walking on solid concrete floors for pigs. Kinematic (50 Hz video recordings in the sagittal plane) and kinetic (1 KHz force plate measuring three perpendicular ground reaction forces) data were collected from four strides of both the fore- and hindlimbs of 30 healthy pigs walking on dry, greasy and wet concrete floor with 10 pigs on each floor condition. The COF of the floor conditions were tested in a drag-test. The results from the gait analysis showed that the pigs adapted their gait to potentially slippery floors by lowering their walking speed and reducing their peak utilised COF on greasy and wet (contaminated) floors compared with dry floors. Moreover, the pigs shortened their progression length and prolonged their stance phase duration on greasy floor compared with dry and wet floors. Thus the greasy floor appeared the most slippery condition to the pigs, whereas the wet floor was intermediate to the other two conditions. The pigs walked with a four-beat gait, and the limbs differed biomechanically, as the forelimbs carried more load, received higher peak vertical forces and had longer lasting stance phases than did the hindlimbs. The utilised COF from the gait analysis indicated that a high floor COF (>0.63) is needed to prevent pigs from slipping and thus to ensure safe walking on dry concrete floors.
In this paper, we propose a generic framework for 3D surface remeshing. Based on a metric-driven Discrete Voronoi Diagram construction, our output is an optimized 3D triangular mesh with a user defined vertex budget. Our approach can deal with a wide range of applications, from high quality mesh generation to shape approximation. By using appropriate metric constraints the method generates isotropic or anisotropic elements. Based on point-sampling, our algorithm combines the robustness and theoretical strength of Delaunay criteria with the efficiency of entirely discrete geometry processing . Besides the general described framework, we show experimental results using isotropic, quadric-enhanced isotropic and anisotropic metrics which prove the efficiency of our method on large meshes, for a low computational cost.
Point set registration is a key component in many computer vision tasks. The goal of point set registration is to assign correspondences between two sets of points and to recover the transformation that maps one point set to the other. Multiple factors, including an unknown nonrigid spatial transformation, large dimensionality of point set, noise, and outliers, make the point set registration a challenging problem. We introduce a probabilistic method, called the Coherent Point Drift (CPD) algorithm, for both rigid and nonrigid point set registration. We consider the alignment of two point sets as a probability density estimation problem. We fit the Gaussian mixture model (GMM) centroids (representing the first point set) to the data (the second point set) by maximizing the likelihood. We force the GMM centroids to move coherently as a group to preserve the topological structure of the point sets. In the rigid case, we impose the coherence constraint by reparameterization of GMM centroid locations with rigid parameters and derive a closed form solution of the maximization step of the EM algorithm in arbitrary dimensions. In the nonrigid case, we impose the coherence constraint by regularizing the displacement field and using the variational calculus to derive the optimal transformation. We also introduce a fast algorithm that reduces the method computation complexity to linear. We test the CPD algorithm for both rigid and nonrigid transformations in the presence of noise, outliers, and missing points, where CPD shows accurate results and outperforms current state-of-the-art methods.
In vitro electromechanical and biomechanical testing of articular cartilage provide critical information about the structure and function of this tissue. Difficulties obtaining fresh tissue and lengthy experimental testing procedures often necessitate a storage protocol, which may adversely affect the functional properties of cartilage. The effects of storage at either 4°C for periods of 6 days and 12 days, or during a single freeze-thaw cycle at -20°C were examined in young bovine cartilage. Non-destructive electromechanical measurements and unconfined compression testing on 3 mm diameter disks were used to assess cartilage properties, including the streaming potential integral (SPI), fibril modulus (Ef), matrix modulus (Em), and permeability (k). Cartilage disks were also examined histologically. Compared with controls, significant decreases in SPI (to 32.3±5.5% of control values, p<0.001), Ef (to 31.3±41.3% [corrected] of control values, p=0.046), Em (to 6.4±8.5% of control values, p<0.0001), and an increase in k (to 2676.7±2562.0% of control values, p=0.004) were observed at day 12 of refrigeration at 4°C, but no significant changes were detected at day 6. A trend toward detecting a decrease in SPI (to 94.2±6.2% of control values, p=0.083) was identified following a single freeze-thaw cycle, but no detectable changes were observed for any biomechanical parameters. All numbers are mean±95% confidence interval. These results indicate that fresh cartilage can be stored in a humid chamber at 4°C for a maximum of 6 days with no detrimental effects to cartilage electromechanical and biomechanical properties, while one freeze-thaw cycle produces minimal deterioration of biomechanical and electromechanical properties. A comparison to literature suggested that particular attention should be paid to the manner in which specimens are thawed after freezing, specifically by minimizing thawing time at higher temperatures.
To determine the spatial variation of in vivo cartilage T2 in young asymptomatic adults.
Quantitative T2 maps of seven asymptomatic young male adults and one male volunteer with a history of previous intraarticular chondroid fragments were calculated by using a multiecho, spin-echo magnetic resonance imaging sequence at 3.0 T. The T2 maps were bilinearly interpolated to generate T2 profiles across the thickness of cartilage.
All seven asymptomatic volunteers demonstrated a monotonic increase in T2, which increased from 32 msec +/- 1 in the deep radial zone and 48 msec +/- 1 in the deep transitional zone to 67 msec +/- 2 in the outer transitional superficial zone. The T2 profile of the volunteer with superficial fibrillation observed at arthroscopy demonstrated marked spatial heterogeneity and a statistically significant increase in cartilage T2.
There is a reproducible pattern of increasing T2 that is proportional to the known spatial variation in cartilage water and is inversely proportional to the distribution of proteoglycans. The authors postulate that these regional T2 differences are secondary to the restricted mobility of cartilage water within an anisotropic solid matrix.
To determine if age and early symptomatic degeneration alter the spatial dependency of cartilage T2.
In 25 asymptomatic volunteers and six volunteers with symptoms of patellar chondromalacia, quantitative T2 maps of patellar cartilage were obtained with a multiecho, spin-echo magnetic resonance imaging sequence at 3.0 T. Spatial variation in T2 was evaluated as a function of participant age and symptoms.
All asymptomatic volunteers demonstrated a continuous increase in T2 from the radial zone to the articular surface. In the population aged 46-60 years compared with younger volunteers, there was a statistically significant (P < .05) increase in T2 of the transitional zone. In symptomatic volunteers, the increase in T2 was larger in magnitude and focal in distribution. In five of the six symptomatic volunteers, the increase in T2 was greater than the 95% prediction interval determined from data in the corresponding age-matched asymptomatic population.
Aging is associated with an asymptomatic increase in T2 of the transitional zone of articular cartilage. Preliminary results indicate this diffuse increase in T2 in senescent cartilage is different in appearance than the focally increased T2 observed in damaged articular cartilage.
Functional neuroimaging data embodies a massive multiple testing problem, where 100,000 correlated test statistics must be assessed. The familywise error rate, the chance of any false positives is the standard measure of Type I errors in multiple testing. In this paper we review and evaluate three approaches to thresholding images of test statistics: Bonferroni, random field and the permutation test. Owing to recent developments, improved Bonferroni procedures, such as Hochberg's methods, are now applicable to dependent data. Continuous random field methods use the smoothness of the image to adapt to the severity of the multiple testing problem. Also, increased computing power has made both permutation and bootstrap methods applicable to functional neuroimaging. We evaluate these approaches on t images using simulations and a collection of real datasets. We find that Bonferroni-related tests offer little improvement over Bonferroni, while the permutation method offers substantial improvement over the random field method for low smoothness and low degrees of freedom. We also show the limitations of trying to find an equivalent number of independent tests for an image of correlated test statistics.
Knowledge of the deformational behaviour of articular cartilage in vivo is required to understand the pathogenesis of osteoarthritis and the mechanical target environment of prospective cartilage transplant recipients.
To study the in vivo deformational behaviour of patellar and femorotibial cartilage for different types of physiological activities; and to test the hypothesis that in vivo deformation of cartilage is modified by intense physical exercise.
Magnetic resonance imaging and 3D digital image analysis were used to determine cartilage volume before and after physical activity in the patella of 12 volunteers (knee bends, squatting, normal gait, running, cycling). Deformation of femorotibial cartilage was investigated in 10 subjects (knee bends, static compression, high impact loading). Patellar cartilage deformation after knee bends was compared in seven professional weight lifters, seven sprinters, and 14 untrained volunteers.
Patellar cartilage deformation was -5.9% after knee bends, -4.7% after squatting, -2.8% after normal walking, -5.0% after running, and -4.5% after cycling. The pattern of patellar cartilage deformation corresponded to the range of motion involved in the particular activity. Tibial cartilage deformation was greatest under high impact loading (-7%), but small for other activities. No significant difference was found between athletes and non-athletic controls.
Patellar cartilage deformation shows a "dose dependent" response, where more intense loading leads to greater deformation. Relatively little deformation was observed in the femorotibial joint, except during high impact activities. The findings provide no evidence that adult human cartilage properties are amendable to training effects in vivo.
Objective:
This proof-of-principle study integrates joint reaction forces (JRFs) and bone shape to assess acute cartilage changes from walking and cycling.
Methods:
Sixteen women with symptomatic knee osteoarthritis were recruited. Biomechanical assessment estimated JRFs during walking and cycling. Subsamples had magnetic resonance imaging (MRI) performed before and after a 25-min walking (n = 7) and/or cycling (n = 9) activity. MRI scans were obtained to assess cartilage shape and composition (T2 relaxation time). Bone shape was quantified using a statistical shape model built from 13 local participants and 100 MRI scans from the Osteoarthritis Initiative. Statistical parametric mapping quantified cartilage change and correlations between cartilage change with JRFs and statistical shape model features.
Results:
Cartilage thickness (interior lateral, Δ - 0.10 mm) and T2 (medial, Δ - 4 ms) decreased on the tibial plateau. On the femur, T2 change depended on the activity. Greater tibiofemoral JRF was associated with more cartilage deformation on the lateral femoral trochlea after walking (r - 0.56). Knees more consistent with osteoarthritis showed smaller decreases in tibial cartilage thickness.
Discussion:
Walking and cycling caused distinct patterns of cartilage deformation, which depended on knee JRFs and bone morphology. For the first time, these results show that cartilage deformation is dependent on bone shapes and JRFs in vivo.
Background
It is unknown whether a greater accumulation of knee load over a typical day is related to how cartilage responds to an acute bout of loading. This information may clarify the role of habitual activity on cartilage function.
Research Question
Is there a relationship between change in tibial and femoral cartilage thickness, volume, and T2 relaxation time following running with daily cumulative knee load in women? Secondarily, is there a relationship between cartilage change following running and the statistical interaction of body mass index (BMI) and daily steps?
Methods
Participants (n = 15) completed gait analyses and wore an accelerometer over a week. Daily cumulative knee load was the statistical interaction between tibial compressive joint reaction force (JRF) impulse with the average number of daily steps measured using accelerometry. Magnetic resonance imaging scans were acquired before and immediately after 15-minutes of treadmill running. Changes in tibial and femoral cartilage thickness, volume, and T2 relaxation time were calculated. Multiple linear regressions tested the associations of cartilage change outcomes with: baseline (thickness, volume, T2), JRF impulse, steps, and the interaction JRF impulse*steps. Secondarily, BMI was substituted for JRF impulse.
Results and Significance
Tibial volume change was explained by baseline volume, JRF impulse, steps, and JRF impulse*steps (R² = 0.50, p = 0.013). Additionally, tibial volume change was explained by baseline volume, BMI, steps, and BMI*steps (R² = 0.43, p = 0.002). Those who were more physically active with lower JRF impulse (or lower BMI) showed less change in tibial cartilage after a running exposure. This may suggest cartilage conditioning.
Objectives
When measuring changes in knee cartilage thickness in vivo after loading, mean values may not reflect local changes. The objectives of this investigation were: (1) use statistical parametric mapping (SPM) to determine regional deformation patterns of tibiofemoral cartilage in response to running; (2) quantify regional differences in cartilage thickness between males and females; and (3) explore the influence of sex on deformation.Materials and methodsAsymptomatic males (n = 15) and females (n = 15) had MRI imaging of their right knee before and after 15 min of treadmill running. Medial and lateral tibial, and medial and lateral weight-bearing femoral cartilage were segmented. SPM was completed on cartilage thickness maps to test the main effects of Running and Sex, and their interaction. F-statistic maps were thresholded; clusters above this threshold indicated significant differences.ResultsDeformation was observed in all four compartments; the lateral tibia had the largest area of deformation (p < 0.0001). Thickness differences between sexes were observed in all four compartments, showing females have thinner cartilage (p ≤ 0.009). The lateral tibia had small clusters indicating an interaction of sex on deformation (p ≤ 0.012).DiscussionSPM identified detailed spatial information on tibiofemoral cartilage thickness differences observed after running, and between sexes and their interaction.
Background:
There are currently limited human in vivo data characterizing the role of the meniscus in load distribution within the tibiofemoral joint. Purpose/Hypothesis: To compare the strains experienced in regions of articular cartilage covered by the meniscus to regions of cartilage not covered by the meniscus. We 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.This article is protected by copyright. All rights reserved
Non-invasive techniques for quantifying early biochemical and biomechanical changes in articular cartilage may provide a means of more precisely assessing osteoarthritis (OA) progression. The goals of this study were to determine the relationship between T1rho magnetic resonance (MR) imaging relaxation times and changes in cartilage composition, cartilage mechanical properties, and synovial fluid biomarker levels and to demonstrate the application of T1rho imaging to evaluate cartilage composition in human subjects in vivo. Femoral condyles and synovial fluid were harvested from healthy and OA porcine knee joints. Sagittal T1rho relaxation MR images of the condyles were acquired. OA regions of OA joints exhibited an increase in T1rho relaxation times as compared to non-OA regions. Furthermore in these regions, cartilage sGAG content and aggregate modulus decreased, while percent degraded collagen and water content increased. In OA joints, synovial fluid concentrations of sGAG decreased and C2C concentrations increased compared to healthy joints. T1rho relaxation times were negatively correlated with cartilage and synovial fluid sGAG concentrations and aggregate modulus and positively correlated with water content and permeability. Additionally, we demonstrated the application of these in vitro findings to the study of human subjects. Specifically, we demonstrated that walking results in decreased T1rho relaxation times, consistent with water exudation and an increase in proteoglycan concentration with in vivo loading. Together, these findings demonstrate that cartilage MR imaging and synovial fluid biomarkers provide powerful non-invasive tools for characterizing changes in the biochemical and biomechanical environment of the joint.
Recently, Eklund et al. (2016) analyzed clustering methods in standard FMRI packages: AFNI (which we maintain), FSL, and SPM [1]. They claimed: 1) false positive rates (FPRs) in traditional approaches are greatly inflated, questioning the validity of "countless published fMRI studies"; 2) nonparametric methods produce valid, but slightly conservative, FPRs; 3) a common flawed assumption is that the spatial autocorrelation function (ACF) of FMRI noise is Gaussian-shaped; and 4) a 15-year-old bug in AFNI's 3dClustSim significantly contributed to producing "particularly high" FPRs compared to other software. We repeated simulations from [1] (Beijing-Zang data [2], see [3]), and comment on each point briefly.
Purpose:
To compare the acute effect of running and bicycling of an equivalent cumulative load on knee cartilage composition and morphometry in healthy young men. A secondary analysis investigated the relationship between activity history and the change in cartilage composition after activity.
Methods:
In fifteen men (25.8±4.2 years), the vertical ground reaction force was measured to determine the cumulative load exposure of a 15-min run. The vertical pedal reaction force was recorded during bicycling to define the bicycling duration of an equivalent cumulative load. On separate visits that were spaced on average 17 days apart, participants completed these running and bicycling bouts. Mean cartilage transverse relaxation times (T2) were determined for cartilage on the tibia and weight-bearing femur before and after each exercise. T2 was measured using a multi-echo spin-echo sequence and 3T MRI. Cartilage of the weight bearing femur and tibia was segmented using a highly-automated segmentation algorithm. Activity history was captured using the International Physical Activity Questionnaire.
Results:
The response of T2 to bicycling and running was different (p=0.019; mean T2: pre-running=34.27ms, pre-bicycling=32.93ms, post-running=31.82ms, post-bicycling=32.36ms). While bicycling produced no change (-1.7%, p=0.300), running shortened T2 (-7.1%, p<0.001). Greater activity history predicted smaller changes in tibial, but not femoral, T2.
Conclusions:
Changes in knee cartilage vary based on activity type, independent of total load exposure, in healthy young men. Smaller changes in T2 were observed after bicycling relative to running. Activity history was inversely related to tibial T2, suggesting cartilage conditioning.
Context:
Osteoarthritis (OA) is a common, worldwide disorder. Magnetic resonance (MR) imaging can directly and noninvasively evaluate articular cartilage and has emerged as an essential tool in the study of OA.
Evidence acquisition:
A PubMed search was performed using the keywords quantitative MRI and cartilage. No limits were set on the range of years searched. Articles were reviewed for relevance with an emphasis on in vivo studies performed at 3 tesla.
Study design:
Clinical review.
Level of evidence:
Level 4.
Results:
T2, T2*, T1 (particularly when measured after exogenous contrast administration, such as with the delayed gadolinium-enhanced MR imaging of cartilage [dGEMRIC] technique), and T1ρ are among the most widely utilized quantitative MR imaging techniques to evaluate cartilage and have been implemented in various patient cohorts. Existing challenges include reproducibility of results, insufficient consensus regarding optimal sequences and parameters, and interpretation of values.
Conclusion:
Quantitative assessment of cartilage using MR imaging techniques likely represents the best opportunity to identify early cartilage degeneration and to follow patients after treatment. Despite existing challenges, ongoing work and unique approaches have shown exciting and promising results.
Altered cartilage loading is believed to be associated with osteoarthritis development. However, there are limited data regarding the influence of normal gait, an essential daily loading activity, on cartilage strains. In this study, 8 healthy subjects with no history of knee surgery or injury underwent magnetic resonance imaging of a single knee prior to and following a 20-minute walking activity at approximately 1.1 m/s. Bone and cartilage surfaces were segmented from these images and compiled into 3-dimensional models of the tibia, femur, and associated cartilage. Thickness changes were measured across a grid of evenly spaced points spanning the models of the articular surfaces. Averaged compartmental strains and local strains were then calculated. Overall compartmental strains after the walking activity were found to be significantly different from zero in all four tibiofemoral compartments, with tibial cartilage strain being significantly larger than femoral cartilage strain. These results provide baseline data regarding the normal tibiofemoral cartilage strain response to gait. Additionally, the technique employed in this study has potential to be used as a “stress test” to understand how factors including age, weight, and injury influence tibiofemoral cartilage strain response, essential information in the development of potential treatment strategies for the prevention of osteoarthritis.
Recent advances in the development of new drugs to halt or even reverse the progression of Osteoarthritis at an early-stage requires new tools to detect early degeneration of articular cartilage. We investigated the ability of an electromechanical probe and an automated indentation technique to characterize entire human articular surfaces for rapid non-destructive discrimination between early degenerated and healthy articular cartilage. Human cadaveric asymptomatic articular surfaces (4 pairs of distal femurs and 4 pairs of tibial plateaus) were used. They were assessed ex vivo: macroscopically, electromechanically (maps of the electromechanical quantitative parameter, QP, reflecting streaming potentials), mechanically (maps of the instantaneous modulus, IM) and through cartilage thickness. Osteochondral cores were also harvested from healthy and degenerated regions for histological assessment, biochemical analyses and unconfined compression tests. The macroscopic visual assessment delimited three distinct regions on each articular surface: region I was macroscopically degenerated, region II was macroscopically normal but adjacent to region I and region III was the remaining normal articular surface. Thus, each extracted core was assigned to one of the three regions. A mixed effect model revealed that only the QP (p < 0.0001) and IM (p < 0.0001) were able to statistically discriminate the three regions. Effect size was higher for QP and IM than other assessments, indicating greater sensitivity to distinguish early degeneration of cartilage. When considering the mapping feature of the QP and IM techniques, it also revealed bilateral symmetry in a moderately similar distribution pattern between bilateral joints. This article is protected by copyright. All rights reserved.
Objective:
The hand-held Arthro-BST™ device is used to map electromechanical properties of articular cartilage. The purpose of the study was to evaluate correlation of electromechanical properties with histological, biochemical and biomechanical properties of cartilage.
Method:
Electromechanical properties (quantitative parameter (QP)) of eight human distal femurs were mapped manually ex vivo using the Arthro-BST (1 measure/site, 5 s/measure, 3209 sites). Osteochondral cores were then harvested from different areas on the femurs and assessed with the Mankin histological score. Prior to histoprocessing, cores were tested in unconfined compression. A subset of the cores was analyzed with polarized light microscopy (PLM) to assess collagen structure. Biochemical assays were done on additional cores to obtain water content and glycosaminoglycan (GAG) content. The QP corresponding to each core was calculated by averaging all QPs collected within 6 mm of the core center.
Results:
The electromechanical QP correlated strongly with both the Mankin score and the PLM score (r = 0.73, P < 0.0001 and r = -0.70, P < 0.0001 respectively) thus accurately reflecting tissue quality and collagen architecture. Electromechanical QP also correlated strongly with biomechanical properties including fibril modulus (r = -0.76, P < 0.0001), matrix modulus (r = -0.69, P < 0.0001), and log of permeability (r = 0.72, P < 0.0001). The QP correlated weakly with GAG per wet weight and with water content (r = -0.50, P < 0.0003 and r = 0.39, P < 0.006 respectively).
Conclusion:
Non-destructive electromechanical QP measurements correlate strongly with histological scores and biomechanical parameters providing a rapid and reliable assessment of articular cartilage quality.
Understanding the acute response of healthy knee cartilage to running may provide valuable insight into functional properties. In recent years, quantitative magnetic resonance (MR) imaging techniques (T1(ρ) and T2 relaxation measurement) have shown tremendous potential and unique ability to noninvasively and quantitatively determine cartilage response to physiologic levels of loading occurring with physiologic levels of exercise.
To measure the short-term changes in MR T1(ρ) and T2 relaxation times of knee articular cartilage and meniscus in healthy individuals immediately after 30 minutes of running.
Descriptive laboratory study.
Twenty young healthy volunteers, aged 22 to 35 years, underwent 3T MR imaging of the knee before and immediately after 30 minutes of running. Quantitative assessment of the cartilage and menisci was performed using MR images with a T1(ρ) and T2 mapping technique. After adjusting for age, sex, and body mass index, repeated-measures analysis of variance was used to determine the effects of running on MR relaxation times.
The post-run T1(ρ) and T2 measurement showed significant reduction in all regions of cartilage except the lateral tibia when compared with the pre-run condition. The medial tibiofemoral (T1(ρ): 9.4%, P < .0001; T2: 5.4%, P = .0049) and patellofemoral (T1(ρ): 12.5%, P < .0001; T2: 5.7%, P = .0007) compartments experienced the greatest reduction after running. The superficial layer of the articular cartilage showed significantly higher change in relaxation times than the deep layer (T1(ρ): 9.6% vs 8.2%, P = .050; T2: 6.0% vs 3.5%, P = .069). The anterior and posterior horns of the medial meniscus (9.7%, P = .016 and 11.4%, P = .001) were the only meniscal subregions with significant changes in T1(ρ) after running.
Shorter T1(ρ) and T2 values after running suggest alteration in the water content and collagen fiber orientation of the articular cartilage. Greater changes in relaxation times of the medial compartment and patellofemoral joint cartilage indicate greater load sharing by these areas during running.
I provide a selective review of the literature on the multiple testing problem in fMRI. By drawing connections with the older modalities, PET in particular, and how software implementations have tracked (or lagged behind) theoretical developments, my narrative aims to give the methodological researcher a historical perspective on this important aspect of fMRI data analysis.
The algorithm can be programmed without the use of multiplication or division. It was found that 333 core locations were sufficient for an IBM 1401 program (used to control an IBM 1627). The average computation time between successive incrementations was approximately 1.5 milliseconds.
Biomechanical factors play an important role in the health of diarthrodial joints. Altered joint loading - associated to obesity, malalignment, trauma or joint instability - is a critical risk factor for joint degeneration, whereas exercise and weight loss have generally been shown to promote beneficial effects for osteoarthritic joints. The mechanisms by which mechanical stress alters the physiology or pathophysiology of articular cartilage or other joint tissues likely involve complex interactions with genetic and molecular influences, particularly local or systemic inflammation secondary to injury or obesity. Chondrocytes perceive physical signals from their environment using a variety of mechanisms, including ion channels, integrin-mediated connections to the extracellular matrix that involve membrane, cytoskeletal and intracellular deformation. An improved understanding of the biophysical and molecular pathways involved in chondrocyte mechanotransduction can provide insight into the development of novel therapeutic approaches for osteoarthritis.
The origin of patellofemoral pain (PFP) may be associated with the inability of the patellofemoral joint cartilage to absorb and distribute patellofemoral joint forces.
When compared with a pain-free control group, young active women with PFP will demonstrate differences in their baseline patellar cartilage thickness and transverse (T2) relaxation time, as well as a less adaptive response to an acute bout of joint loading.
Controlled laboratory study; Level of evidence, 3.
Ten women between the ages of 23 to 37 years with PFP and 10 sex-, age-, and activity-matched pain-free controls participated. Quantitative magnetic resonance imaging of the patellofemoral joint was performed at baseline and after participants performed 50 deep knee bends. Differences in baseline cartilage thickness and T2 relaxation time, as well as the postexercise change in patellar cartilage thickness and T2 relaxation time, were compared between groups.
Individuals with PFP demonstrated reductions in baseline cartilage thickness of 14.0% and 14.1% for the lateral patellar facet and total patellar cartilage, respectively. Similarly, individuals with PFP exhibited significantly lower postexercise cartilage thickness change for the lateral patellar facet (2.1% vs 8.9%) and the total patellar cartilage (4.4% vs 10.0%) when compared with the control group. No group differences in baseline or postexercise change in T2 relaxation time were found.
The findings suggest that a baseline reduction in patellar cartilage thickness and a reduced deformational behavior of patellar cartilage following an acute bout of loading are associated with presence of PFP symptoms.
Physiological magnetic resonance imaging (MRI) under loading or knee malalignment conditions has not been thoroughly investigated. We assessed the influence of static loading and knee alignment on T2 (transverse relaxation time) mapping of the knee femoral cartilage of porcine knee joints using a non-metallic pressure device.
Ten porcine knee joints were harvested en bloc with intact capsules and surrounding muscles and imaged using a custom-made pressure device and 3.0-T MRI system. Sagittal T2 maps were obtained (1) at knee neutral alignment without external loading (no loading), (2) under mechanical compression of 140 N (neutral loading), and (3) under the same loading conditions as in (2) with the knee at 10 degrees varus alignment (varus loading). T2 values of deep, intermediate, and superficial zones of the medial and lateral femoral cartilages at the weight-bearing area were compared among these conditions using custom-made software. Cartilage contact pressure between the femoral and tibial cartilages, measured by a pressure-sensitive film, was correlated with cartilage T2 measurements.
In the medial cartilage, mean T2 values of the deep, intermediate, and superficial zones decreased by 1.4%, 13.0%, and 6.0% under neutral loading. They further decreased by 4.3%, 19.3%, and 17.2% under varus loading compared to no loading. In the lateral cartilage, these mean T2 values decreased by 3.9%, 7.7%, and 4.2% under neutral loading, but increased by 1.6%, 9.6%, and 7.2% under varus loading. There was a significant decrease in T2 values in the intermediate zone of the medial cartilage under both neutral and varus loading, and in the superficial zone of the medial cartilage under varus loading (P<0.05). Total contact pressure values under neutral loading and varus loading conditions significantly correlated with T2 values in the superficial and intermediate zones of the medial cartilages.
The response of T2 to change in static loading or alignment varied between the medial and lateral cartilages, and among the deep, intermediate, and superficial zones. These T2 changes were significantly related to the contact pressure measurements. Our results indicate that T2 mapping under loading allows non-invasive, biomechanical assessment of site-specific stress distribution in the cartilage.
Studies have shown that functional analysis of knee cartilage based on magnetic resonance (MR) relaxation times is a valuable tool in the understanding of osteoarthritis (OA). In this work, the regional spatial distribution of knee cartilage T1rho, and T2 relaxation times based on texture and laminar analyses was studied to investigate if they provide additional insight compared to global mean values in the study of OA.
Knee cartilage of 36 subjects, 19 healthy controls and 17 with mild OA, was divided into 16 compartments. T1rho and T2 relaxation times were studied with first order statistics, eight texture parameters with four different orientations using gray-level co-occurrence matrices and by subdividing each compartment into two different layers: Deep and superficial. Receiver operating characteristic curve analysis was performed to evaluate the potential of each technique to correctly classify the populations.
Although the deep and superficial cartilage layers had in general significantly different T1rho and T2 relaxation times, they performed similarly in terms of subject discrimination. The subdivision of lateral and medial femoral compartments into weight-bearing and non-weight-bearing regions did not improve discrimination. Also it was found that the most sensitive region was the patella and that T1rho discriminated better than T2. The most important finding was that with respect to global mean values, laminar and texture analyses improved subject discrimination.
Results of this study suggest that spatially assessing MR images of the knee cartilage relaxation times using laminar and texture analyses could lead to better and probably earlier identification of cartilage matrix abnormalities in subjects with OA.
This study demonstrates the in vitro displacement and strain of articular cartilage in a cyclically-compressed and intact joint using displacement-encoded imaging with stimulated echoes (DENSE) and fast spin echo (FSE). Deformation and strain fields exhibited complex and heterogeneous patterns. The displacements in the loading direction ranged from -1688 to -1481 microm in the tibial cartilage and from -1601 to -764 microm in the femoral cartilage. Corresponding strains ranged from -9.8% to 0.7% and from -4.3% to 0.0%. The displacement and strain precision were determined to be 65 microm and less than 0.2%, respectively. Displacement-encoded magnetic resonance imaging is capable of determining the nonuniform displacements and strains in the articular cartilage of an intact joint to a high precision. Knowledge of these nonuniform strains is critical for the in situ characterization of normal and diseased tissue, as well as the comprehensive evaluation of repair constructs designed using regenerative medicine.
The objective of this study was to evaluate the correlations between MR parameters and the biomechanical properties of naturally degenerated human articular cartilage. Human cartilage explants from the femoral condyles of patients who underwent total knee replacement were evaluated on a micro-imaging system at 3T. To quantify glycosaminoglycan (GAG) content, delayed gadolinium-enhanced MRI of the cartilage (dGEMRIC) was used. T(2) maps were created by using multi-echo, multi-slice spin echo sequences with six echoes: 15, 30, 45, 60, 75, and 90 ms. Data for apparent diffusion constant (ADC) maps were obtained from pulsed gradient spin echo (PGSE) sequences with five b-values: 10.472, 220.0, 627.0, 452.8, 724.5, and 957.7. MR parameters were correlated with mechanical parameters (instantaneous (I) and equilibrium (Eq) modulus and relaxation time (tau)), and the OA stage of each cartilage specimen was determined by histological evaluation of hematoxylin-eosin stained slices. For some parameters, a high correlation was found: the correlation of T(1Gd) vs Eq (r=0.8095), T(1Gd) vs I/Eq (r=-0.8441) and T(1Gd) vs tau (r=0.8469). The correlation of T(2) and ADC with selected biomechanical parameters was not statistically significant. In conclusion, GAG content measured by dGEMRIC is highly related to the selected biomechanical properties of naturally degenerated articular cartilage. In contrast, T(2) and ADC were unable to estimate these properties. The results of the study imply that some MR parameters can non-invasively predict the biomechanical properties of degenerated articular cartilage.
A mathematical model is developed for indentation tests of articular cartilage. The cartilage, normally bonded to the subchondral bone, is modeled as an infinite elastic layer bonded to a rigid half space, and the indenter is assumed to be a rigid axisymmetric punch. The problem is formulated as a mixed boundary value problem of the theory of elasticity and solutions are obtained for the indentation of the layer by the plane end of a rigid circular cylinder and by a rigid sphere. Subject to detailed verification with independent tests, the present solutions are suggested as useful for the determination of the elastic shear modulus of intact cartilage.
This review is aimed at unifying our understanding of cartilage viscoelastic properties in compression, in particular the role of compression-dependent permeability in controlling interstitial fluid flow and its contribution to the observed viscoelastic effects. During the previous decade, it was shown that compression causes the permeability of cartilage to drop in a functional manner described by k = ko exp (epsilon M) where ko and M were defined as intrinsic permeability parameters and epsilon is the dilatation of the solid matrix (epsilon = tr delta u). Since permeability is inversely related to the diffusive drag coefficient of relative fluid motion with respect to the porous solid matrix, the measured load-deformation response of the tissue must therefore also depend on the non-linearly permeable nature of the tissue. We have summarized in this review our understanding of this non-linear phenomenon. This understanding of these flow-dependent viscoelastic effects are put into the historical perspective of a comprehensive literature review of earlier attempts to model the compressive viscoelastic properties of articular cartilage.
Unlabelled:
In a series of 103 specimens from the lateral facet of the human patella, the intrinsic mechanical properties of articular cartilage were measured using a confined compression creep test. By considering the cartilage as a porous, permeable solid filed with fluid, this experimental procedure allowed the determination of the intrinsic equilibrium modulus of the cartilage matrix and its permeability to fluid flow. The intrinsic equilibrium modulus and the permeability both were highly correlated with the water content of the tissue; as water content increased, the matrix of the tissue became softer and more permeable. There was only a marginal decrease in the equilibrium modulus of the tissue with increasing age and surface degeneration. The permeability of the cartilage matrix was not significantly correlated with age or degeneration.
Clinical relevance:
We concluded that the visual or histological appearance of a cartilage specimen may be a poor indicator of its ability to function as the bearing material in the intact joint. A more reliable indicator of the functional properties of a specimen can be obtained either by direct mechanical testing or by biochemical analysis of its composition.
This study addresses the hypothesis that interstitial fluid plays a major role in the load support mechanism of articular cartilage. An asymptotic solution is presented for two contacting biphasic cartilage layers under compression. This solution is valid for identical thin (i.e. epsilon = h'/a'0 < 1), frictionless cartilage layers, and for the 'early' time response (i.e. t' < (h')2/HAk) after the application of a step load. An equilibrium asymptotic solution is also presented (i.e.t'-->infinity). Here h' is the thickness, a'0 is a characteristic contact radius, HA is the aggregate modulus and k is the permeability of the cartilage layer. A main conclusion from this analysis is that the fluid phase of cartilage plays a major role in providing load support during the first 100-200 s after contact loading. Further, the largest component of stress in cartilage is the hydrostatic pressure developed in the interstitial fluid. For tissue fluid volume fraction (porosity) in the range 0.6 < or = phi f < or = 0.8, k = O(10(-15) m4/Ns) and HA = O(1 MPa), the peak magnitude of the principal effective (or elastic) stress may be as low as 14% of the peak hydrostatic pressure within the tissue, or the contact stress at the surface. In effect, the interstitial fluid shields the solid matrix from high normal stresses and strains. The asymptotic solution also shows that pressure-sensitive film measurements of intra-articular contact stress do not measure the elastic stress at the surface, but they rather provide a measure of the interstitial fluid pressure. Finally, this analysis provides strong support for the hypothesis that, if sudden loading causes shear failure within the cartilage-bone layer structure, this failure would take place at the cartilage-bone interface, and the plane of failure would be either parallel or perpendicular to this interface.
Biphasic creep indentation methodology and an automated indentation apparatus were used to measure the aggregate modulus, Poisson's ratio, permeability, thickness, creep and recovery equilibrium times, and percentage of recovery of normal articular cartilage in 10 human hip joints. These properties were mapped regionally to examine the mechanical factors involved in the development of site-specific degenerative lesions in the acetabulum and femoral head. The results indicate that there are significant differences between these properties regionally in the acetabulum and femoral head and between the two anatomical structures. Specifically, it was found that cartilage in the superomedial aspect of the femoral head has a 41% larger aggregate modulus than its anatomically corresponding articulating surface in the acetabulum. In addition, the superomedial aspect of the femoral head has the greatest aggregate modulus (1.816 MPa) within the hip joint. During sitting, the inferior portion of the femoral head is in contact with the anterior acetabulum, and the anterior acetabulum has a 53% greater aggregate modulus than the inferior femoral head. This area below the fovea on the femoral head has the least aggregate modulus (0.814 MPa) within the hip joint. These mismatches in the compressive modulus of opposing articulating surfaces may contribute to degeneration of cartilage in the superomedial acetabulum and the inferior femoral head. Our findings support the clinical observation that these areas are frequent sites of early degeneration.
The function of articular cartilage depends on the interaction between the tissue matrix and the interstitial fluid bound to the proteoglycan molecules. Mechanical loading has been shown to be involved in both the metabolic regulation of chondrocytes and in matrix degeneration. The purpose of the present study was therefore to analyze the deformation, recovery, and fluid flow in human articular cartilage after dynamic loading in vivo. The patellae of 7 volunteers were imaged at physical rest and after performing knee bends, with a specifically optimized fat-suppressed FLASH-3D magnetic resonance (MR) sequence. To measure cartilage deformation, the total volume of the patellar cartilage was determined, employing 3D digital image analysis. Patellar cartilage deformation ranged from 2.4 to 8.6% after 50 knee bends, and from 2.4% to 8.5% after 100 knee bends. Repeated sets of dynamic exercise at intervals of 15 min did not cause further deformation. After 100 knee bends, the cartilage required more than 90 min to recover from loading. The rate of fluid flow during relaxation ranged from 1.1 to 3.5 mm(3)/min (0.08 to 0.22 mm(3)/min per square centimeter of the articular surface) and was highly correlated with the individual degree of deformation after knee bends. The data provide the first quantification of articular cartilage recovery and of the rate of fluid flow between the cartilage matrix and surrounding tissue in intact joints in vivo. Measurement in the living opens the possibility of relating interindividual variations of mechanical cartilage properties to the susceptibility of developing joint failure, to assess the load-partitioning between the fluid phase and solid cartilage matrix during load transfer, and to determine the role of mechanically induced fluid flow in the regulation of the metabolic activity of chondrocytes.
The deformational behavior of articular cartilage has been investigated in confined and unconfined compression experiments and indentation tests, but to date there exist no reliable data on the in situ deformation of the cartilage during static loading. The objective of the current study was to perform a systematic study into cartilage compression of intact human femoro-patellar joints under short- and long-term static loading with MR imaging. A non-metallic pneumatic pressure device was used to apply loads of 150% body weight to six joints within the extremity coil of an MRI scanner. The cartilage was delineated during the compression experiment with previously validated 2D and 3D fat-suppressed gradient echo sequences. We observed a mean (maximal) in situ deformation of 44% (57%) in patellar cartilage after 32 h of loading (mean contact pressure 3.6 MPa), the femoral cartilage showing a smaller amount of deformation than the patella. However, only around 7% of the final deformation (3% absolute deformation) occurred during the first minute of loading. A 43% fluid loss from the interstitial patellar matrix was recorded, the initial fluid flux being 0.217 +/- 0.083 microm/s, and a high inter-individual variability of the deformational behavior (coefficients of variation 11-38%). In conjunction with finite-element analyses, these data may be used to compute the load partitioning between the solid matrix and fluid phase, and to elucidate the etiologic factors relevant in mechanically induced osteoarthritis. They can also provide direct estimates of the mechanical strain to be encountered by cartilage transplants.
The objective of this study was to test the hypothesis that static loading (squatting at a 90 degrees angle) and dynamic loading (30 deep knee bends) cause different extents and patterns of patellar cartilage deformation in vivo. The two activities were selected because they imply different types of joint loading and reflect a realistic and appropriate range of strenuous activity. Twelve healthy volunteers were examined and the volume and thickness of the patellar cartilage determined before and from 90 to 320s after loading, using a water excitation gradient echo MR sequence and a three-dimensional (3D) distance transformation algorithm. Following knee bends, we observed a residual reduction of the patellar cartilage volume (-5.9+/-2.1%; p<0.01) and of the maximal cartilage thickness (-2.8+/-2.6%), the maximal deformation occurring in the superior lateral and the medial patellar facet. Following squatting, the change of patellar cartilage volume was -4.7+/-1.6% (p<0.01) and that of the maximal cartilage thickness -4.9+/-1.4% (p<0.01), the maximal deformation being recorded in the central aspect of the lateral patellar facet. The volume changes were significantly lower after squatting than after knee bends (p<0.05), but the maximal thickness changes higher (p<0.05). The results obtained in this study can serve to validate computer models of joint load transfer, to guide experiments on the mechanical regulation of chondrocyte biosynthesis, and to estimate the magnitude of deformation to be encountered by tissue-engineered cartilage within its target environment.
Quantitative magnetic resonance imaging (MRI) is the most potential non-invasive means for revealing the structure, composition and pathology of articular cartilage. Here we hypothesize that cartilage mechanical properties as determined by the macromolecular framework and their interactions can be accessed by quantitative MRI. To test this, adjacent cartilage disk pairs (n=32) were prepared from bovine proximal humerus and patellofemoral surfaces. For one sample, the tissue Young's modulus, aggregate modulus, dynamic modulus and Poisson's ratio were determined in unconfined compression. The adjacent disk was studied at 9.4T to determine the tissue T(2) relaxation time, sensitive to the integrity of the collagen network, and T(1) relaxation time in the presence of Gd-DTPA, a technique developed for the estimation of cartilage proteoglycan (PG) content. Quantitative MRI parameters were able to explain up to 87% of the variations in certain biomechanical parameters. Correlations were further improved when data from the proximal humerus was assessed separately. MRI parameters revealed a topographical variation similar to that of mechanical parameters. Linear regression analysis revealed that Young's modulus of cartilage may be characterized more completely by combining both collagen- and PG-sensitive MRI parameters. The present results suggest that quantitative MRI can provide important information on the mechanical properties of articular cartilage. The results are encouraging with respect to functional imaging of cartilage, although in vivo applicability may be limited by the inferior resolution of clinical MRI instruments.
Quantitative magnetic resonance imaging (MRI) techniques have earlier been developed to characterize the structure and composition of articular cartilage. Particularly, Gd-DTPA(2-)-enhanced T1 imaging is sensitive to cartilage proteoglycan content, while T2 relaxation time mapping is indicative of the integrity and arrangement of the collagen network. However, the ability of these techniques to detect early osteoarthrotic changes in cartilage has not been demonstrated. In this study, normal and spontaneously degenerated bovine patellar cartilage samples (n=32) were investigated in vitro using the aforementioned techniques. For reference, mechanical, histological and biochemical properties of the adjacent tissue were determined, and a grading system, the cartilage quality index (CQI), was used to score the structural and functional integrity of each sample. As cartilage degeneration progressed, a statistically significant increase in the superficial T2 (r=0.494, p<0.05) and a decrease in superficial and bulk T1 in the presence of Gd-DTPA(2-) (r=-0.681 and -0.688 (p<0.05), respectively) were observed. Gd-DTPA(2-)-enhanced T1 imaging served as the best predictor of tissue integrity and accounted for about 50% of the variation in CQI. The present results reveal that changes in the quantitative MRI parameters studied are indicative of structural and compositional alterations as well as the mechanical impairment of spontaneously degenerated articular cartilage.
The macromolecular structure and mechanical properties of articular cartilage are interrelated and known to vary topographically in the human knee joint. To investigate the potential of delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), T1, and T2 mapping to elucidate these differences, full-thickness cartilage disks were prepared from six anatomical locations in nonarthritic human knee joints (N = 13). Young's modulus and the dynamic modulus at 1 Hz were determined with the use of unconfined compression tests, followed by quantitative MRI measurements at 9.4 Tesla. Mechanical tests revealed reproducible, statistically significant differences in moduli between the patella and the medial/lateral femoral condyles. Typically, femoral cartilage showed higher Young's (>1.0 MPa) and dynamic (>8 MPa) moduli than tibial or patellar cartilage (Young's modulus < 0.9 MPa, dynamic modulus < 8 MPa). dGEMRIC moderately reproduced the topographical variation in moduli. Additionally, T1, T2, and dGEMRIC revealed topographical differences that were not registered mechanically. The different MRI and mechanical parameters showed poor to excellent linear correlations, up to r = 0.87, at individual test sites. After all specimens were pooled, dGEMRIC was the best predictor of compressive stiffness (r = 0.57, N = 77). The results suggest that quantitative MRI can indirectly provide information on the mechanical properties of human knee articular cartilage, as well as the site-dependent variations of these properties. Investigators should consider the topographical variation in MRI parameters when conducting quantitative MRI of cartilage in vivo.
The concentration of glycosaminoglycan (GAG) in articular cartilage is known to be an important determinant of tissue mechanical properties based on numerous studies relating bulk GAG and mechanical properties. To date limited information exists regarding the relationship between GAG and mechanical properties on a spatially-localized basis in intact samples of native tissue. This relation can now be explored by using delayed gadolinium-enhanced MRI of cartilage (dGEMRIC--a recently available non-destructive magnetic resonance imaging method for measuring glycosaminoglycan concentration) combined with non-destructive mechanical indentation testing. In this study, three tibial plateaus from patients undergoing total knee arthroplasty were imaged by dGEMRIC. At 33-44 test locations for each tibial plateau, the load response to focal indentation was measured as an index of cartilage stiffness. Overall, a high correlation was found between the dGEMRIC index (T(1Gd)) and local stiffness (Pearson correlation coefficients r = 0.90, 0.64, 0.81; p < 0.0001) when the GAG at each test location was averaged over a depth of tissue comparable to that affected by the indentation. When GAG was averaged over larger depths, the correlations were generally lower. In addition, the correlations improved when the central and peripheral (submeniscal) areas of the tibial plateau were analyzed separately, suggesting that a factor other than GAG concentration is also contributing to indentation stiffness. The results demonstrate the importance of MRI in yielding spatial localization of GAG concentration in the evaluation of cartilage mechanical properties when heterogeneous samples are involved and suggest the possibility that the evaluation of mechanical properties may be improved further by adding other MRI parameters sensitive to the collagen component of cartilage.
The material properties of articular cartilage in the rabbit tibial plateau were determined using biphasic indentation creep tests. Cartilage specimens from matched-pair hind limbs of rabbits approximately 4 months of age and greater than 12 months of age were tested on two locations within each compartment using a custom built materials testing apparatus. A three-way ANOVA was used to determine the effect of leg, compartment, and test location on the material properties (aggregate modulus, permeability, and Poisson's ratio) and thickness of the cartilage for each set of specimens. While no differences were observed in cartilage properties between the left and right legs, differences between compartments were found in each set of specimens. For cartilage from the adolescent group, values for aggregate modulus were 40% less in the medial compartment compared to the lateral compartment, while values for permeability and thickness were greater in the medial compartment compared to the lateral compartment (57% and 30%, respectively). Values for Poisson's ratio were 19% less in the medial compartment compared to the lateral compartment. There was also a strong trend for thickness to differ between test locations. Similar findings were observed for cartilage from the mature group with values for permeability and thickness being greater in the medial compartment compared to the lateral compartment (66% and 34%, respectively). Values for Poisson's ratio were 22% less in the medial compartment compared to the lateral compartment.