Laser-irradiating infrared attenuated total reflection spectroscopy of articular cartilage: Potential and challenges for diagnosing osteoarthritis.

Objective: A prototype infrared attenuated total reflection (IR-ATR) laser spectroscopic system designed for in vivo classification of human cartilage tissue according to its histological health status during arthroscopic surgery is presented. Prior to real-world in vivo applications, this so-called osteoarthritis (OA) scanner has been tested at in vitro conditions revealing the challenges associated with complex sample matrices and the accordingly obtained sparse spectral datasets. Methods: In vitro studies on human knee cartilage samples at different contact pressures (i.e., 0.2-0.5 â€‹MPa) allowed recording cartilage degeneration characteristic IR signatures comparable to in vivo conditions with high temporal resolution. Afterwards, the cartilage samples were assessed based on the clinically acknowledged osteoarthritis cartilage histopathology assessment (OARSI) system and correlated with the obtained sparse IR data. Results: Amide and carbohydrate signal behavior was observed to be almost identical between the obtained sparse IR data and previously measured FTIR data used for sparse partial least squares discriminant analysis (SPLSDA) to identify the spectral regions relevant to cartilage condition. Contact pressures between 0.3 and 0.4 â€‹MPa seem to provide the best sparse IR spectra for cylindrical (d â€‹= â€‹3 â€‹mm) probe tips. Conclusion: Laser-irradiating IR-ATR spectroscopy is a promising analytical technique for future arthroscopic applications to differentiate healthy and osteoarthritic cartilage tissue. However, this study also revealed that the flexible connection between the laser-based analyzer and the arthroscopic ATR-probe via IR-transparent fiberoptic cables may affect the robustness of the obtained IR data and requires further improvements.

Generalizable Deep Learning-based Sleep Staging Approach for Ambulatory Textile Electrode Headband Recordings.

Reliable, automated, and user-friendly solutions for the identification of sleep stages in home environment are needed in various clinical and scientific research settings. Previously we have shown that signals recorded with an easily applicable textile electrode headband (FocusBand, T 2 Green Pty Ltd) contain characteristics similar to the standard electrooculography (EOG, E1-M2). We hypothesize that the electroencephalographic (EEG) signals recorded using the textile electrode headband are similar enough with standard EOG in order to develop an automatic neural network-based sleep staging method that generalizes from diagnostic polysomnographic (PSG) data to ambulatory sleep recordings of textile electrode-based forehead EEG. Standard EOG signals together with manually annotated sleep stages from clinical PSG dataset (n = 876) were used to train, validate, and test a fully convolutional neural network (CNN). Furthermore, ambulatory sleep recordings including a standard set of gel-based electrodes and the textile electrode headband were conducted for 10 healthy volunteers at their homes to test the generalizability of the model. In the test set (n = 88) of the clinical dataset, the model's accuracy for 5-stage sleep stage classification was 80% (κ = 0.73) using only the single-channel EOG. The model generalized well for the headband-data, reaching 82% (κ = 0.75) overall sleep staging accuracy. In comparison, accuracy of the model was 87% (κ = 0.82) in home recordings using the standard EOG. In conclusion, the CNN model shows potential on automatic sleep staging of healthy individuals using a reusable electrode headband in a home environment.

Infrared spectroscopy is suitable for objective assessment of articular cartilage health.

Objective: To evaluate the feasibility of Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy to detect cartilage degradation due to osteoarthritis and to validate the methodology with osteochondral human cartilage samples for future development towards clinical use. Design: Cylindrical (d â€‹= â€‹4 â€‹mm) osteochondral samples (n â€‹= â€‹349) were prepared from nine human cadavers and measured with FTIR-ATR spectroscopy. Afterwards, the samples were assessed with Osteoarthritis Research Society International (OARSI) osteoarthritis cartilage histopathology assessment system and divided into two groups: 1) healthy (OARSI 0-2) and 2) osteoarthritic (OARSI 2.5-6). The classification was done with partial least squares discriminant analysis model utilizing cross-model validation. Receiver operating characteristics curve analysis was performed and the area under curve (AUC) was calculated. Results: For all samples combined, classification accuracy was 73% with AUC of 0.79. Femoral samples had accuracy of 74% and AUC of 0.77, while tibial samples had accuracy of 66%, and AUC of 0.74. Patellar samples had accuracy of 84% and AUC of 0.91. Conclusions: The results indicate that FTIR-ATR spectroscopy can differentiate between healthy and osteoarthritic femoral, tibial and patellar human tissue. If combined with a fiber optic probe, FTIR-ATR spectroscopy could provide additional objective intraoperative information during arthroscopic surgeries, which could improve clinical outcomes.

Total durations of respiratory events are modulated within REM and NREM sleep by sleeping position and obesity in OSA patients.

BACKGROUND: Supine sleeping position and obesity are well-known risk factors for obstructive sleep apnea (OSA) and modulate the risk for OSA-related daytime symptoms. Although respiratory event durations are associated with OSA-related severe health consequences, it is unclear how sleeping position, obesity, and daytime sleepiness are associated with respiratory event durations during REM and NREM sleep. We hypothesize that irrespective of the apnea-hypopnea index (AHI), respiratory event durations differ significantly between various OSA subgroups during REM and NREM sleep. METHODS: One night in-lab polysomnographic recordings were retrospectively analyzed from 1910 untreated suspected OSA patients. 599 patients (AHI ≥ 5) were included in study and divided into subgroups based on positional dependency, BMI, and daytime sleepiness (Epworth Sleepiness Scale and Multiple Sleep Latency Test). Differences in total hypopnea time (THT), total apnea time (TAT), and total apnea-hypopnea time (TAHT) within REM and NREM sleep between the subgroups were evaluated. RESULTS: During REM sleep, positional OSA patients had lower THT (OR = 0.952, p < 0.001) and TAHT (OR = 0.943, p < 0.001) than their non-positional counterparts. Compared to normal-weight patients (BMI < 25 kg/m2), obese patients (BMI ≥ 30 kg/m2) had lower THT, TAT, and TAHT (ORs = 0.942-0.971, p ≤ 0.009) during NREM sleep but higher THT (OR = 1.057, p = 0.001) and TAHT (OR = 1.052, p = 0.001) during REM sleep. No significant differences were observed in THT, TAT, and TAHT between patients with and without daytime sleepiness. CONCLUSION: Regardless of the AHI, respiratory event durations vary significantly between OSA sub-groups during REM and NREM sleep. Therefore, to personalize OSA severity estimation the diagnosis should be tailored based on patient's demographics, clinical phenotype, and PSG characteristics.

Machine learning augmented near-infrared spectroscopy: In vivo follow-up of cartilage defects.

OBJECTIVE: To assess the potential of near-infrared spectroscopy (NIRS) for in vivo arthroscopic monitoring of cartilage defects. METHOD: Sharp and blunt cartilage grooves were induced in the radiocarpal and intercarpal joints of Shetland ponies and monitored at baseline (0 weeks) and at three follow-up timepoints (11, 23, and 39 weeks) by measuring near-infrared spectra in vivo at and around the grooves. The animals were sacrificed after 39 weeks and the joints were harvested. Spectra were reacquired ex vivo to ensure reliability of in vivo measurements and for reference analyses. Additionally, cartilage thickness and instantaneous modulus were determined via computed tomography and mechanical testing, respectively. The relationship between the ex vivo spectra and cartilage reference properties was determined using convolutional neural network. RESULTS: In an independent test set, the trained networks yielded significant correlations for cartilage thickness (ρ = 0.473) and instantaneous modulus (ρ = 0.498). These networks were used to predict the reference properties at baseline and at follow-up time points. In the radiocarpal joint, cartilage thickness increased significantly with both groove types after baseline and remained swollen. Additionally, at 39 weeks, a significant difference was observed in cartilage thickness between controls and sharp grooves. For the instantaneous modulus, a significant decrease was observed with both groove types in the radiocarpal joint from baseline to 23 and 39 weeks. CONCLUSION: NIRS combined with machine learning enabled determination of cartilage properties in vivo, thereby providing longitudinal evaluation of post-intervention injury development. Additionally, radiocarpal joints were found more vulnerable to cartilage degeneration after damage than intercarpal joints.

Polysomnographic characteristics of severe obstructive sleep apnea vary significantly between hypertensive and normotensive patients of both genders.

PURPOSE: Hypertension is a common finding in patients with obstructive sleep apnea (OSA), but it has remained unclear whether or not the amount of disturbed breathing and characteristics of individual respiratory events differ between hypertensive and normotensive patients with severe OSA. METHODS: Full polysomnographic recordings of 323 men and 89 women with severe OSA were analyzed. Differences in the duration of individual respiratory events, total apnea and hypopnea times, and the percentage of disturbed breathing from total sleep time (AHT%) were compared between normotensive and hypertensive patients separately by genders. Furthermore, differences in the respiratory event characteristics were assessed between three AHT% groups (AHT% ≤ 30%, 30% < AHT% ≤ 45%, and AHT% > 45%). RESULTS: Hypertensive women had lower percentage apnea time (15.2% vs. 18.2%, p = 0.003) and AHT% (33.5% vs. 36.5%, p = 0.021) when compared with normotensive women. However, these differences were not observed between hypertensive and normotensive men. Percentage hypopnea time was higher in hypertensive men (13.5% vs. 11.2%, p = 0.043) but not in women (15.2% vs. 12.2%, p = 0.130) compared with their normotensive counterparts. The variation in AHI explained 60.5% (ρ = 0.778) and 65.0% (ρ = 0.806) of the variation in AHT% in normotensive and hypertensive patients, respectively. However, when AHT% increased, the capability of AHI to explain the variation in AHT% declined. CONCLUSIONS: There is a major inter- and intra-gender variation in percentage apnea and hypopnea times between hypertensive and normotensive patients with severe OSA. OSA is an important risk factor for hypertension and thus, early detection and phenotyping of OSA would allow timely treatment of patients with the highest risk of hypertension.

Comparison of water, hydroxyproline, uronic acid and elastin contents of bovine knee ligaments and patellar tendon and their relationships with biomechanical properties.

Mechanical material properties of ligaments originate from their biochemical composition and structural organization. However, it is not yet fully elucidated how biochemical contents vary between knee ligaments and patellar tendon (PT) and how they relate with mechanical properties. The purpose of this study was to compare water, collagen, proteoglycan and elastin contents between bovine knee ligaments and PT and correlate them with tensile material properties. Hydroxyproline (collagen), uronic acid (proteoglycan) and elastin contents per wet and dry weights were measured using colorimetric biochemical methods for bovine knee ligament and PT samples (n = 10 knees). Direct comparison and correlation with multiple linear regression were performed against biomechanical properties measured in our earlier study. Anterior cruciate ligament (ACL) and PT exhibited lower hydroxyproline content per wet weight compared with other ligaments (p < 0.05). Cruciate ligaments had higher uronic acid content per dry weight compared with collateral ligaments (p < 0.05). Posterior cruciate ligament had higher elastin content than ACL (p < 0.05). Higher hydroxyproline content per wet weight implied higher Young's modulus, strength and toughness. Quantitatively, higher elastin content per wet weight predicted higher toe region nonlinearity and Young's modulus whereas higher uronic acid content per dry weight predicted lower Young's modulus, yield stress and toughness. Differences between ligaments in biochemical composition highlight differences in their physiological function and loading regimes. As expected, collagen content showed similar trend with stiffness and strength. The predictive role of proteoglycan and elastin contents on the mechanical properties might indicate their important functional role in ligaments.

Effects of body mass on microstructural features of the osteochondral unit: A comparative analysis of 37 mammalian species.

Since Galileo's days the effect of size on the anatomical characteristics of the structural elements of the body has been a subject of interest. However, the effects of scaling at tissue level have received little interest and virtually no data exist on the subject with respect to the osteochondral unit in the joint, despite this being one of the most lesion-prone and clinically relevant parts of the musculoskeletal system. Imaging techniques, including Fourier transform infrared imaging, polarized light microscopy and micro computed tomography, were combined to study the response to increasing body mass of the osteochondral unit. We analyzed the effect of scaling on structural characteristics of articular cartilage, subchondral plate and the supporting trabecular bone, across a wide range of mammals at microscopic level. We demonstrated that, while total cartilage thickness scales to body mass in a negative allometric fashion, thickness of different cartilage layers did not. Cartilage tissue layers were found to adapt to increasing loads principally in the deep zone with the superficial layers becoming relatively thinner. Subchondral plate thickness was found to have no correlation to body mass, nor did bone volume fraction. The underlying trabecular bone was found to have thicker trabeculae (r=0.75, p<0.001), as expected since this structure carries most loads and plays a role in force mitigation. The results of this study suggest that the osteochondral tissue structure has remained remarkably preserved across mammalian species during evolution, and that in particular, the trabecular bone carries the adaptation to the increasing body mass.

T2* and quantitative susceptibility mapping in an equine model of post-traumatic osteoarthritis: assessment of mechanical and structural properties of articular cartilage.

OBJECTIVE: To investigate the potential of quantitative susceptibility mapping (QSM) and T2* relaxation time mapping to determine mechanical and structural properties of articular cartilage via univariate and multivariate analysis. METHODS: Samples were obtained from a cartilage repair study, in which surgically induced full-thickness chondral defects in the stifle joints of seven Shetland ponies caused post-traumatic osteoarthritis (14 samples). Control samples were collected from non-operated joints of three animals (6 samples). Magnetic resonance imaging (MRI) was performed at 9.4 T, using a 3-D multi-echo gradient echo sequence. Biomechanical testing, digital densitometry (DD) and polarized light microscopy (PLM) were utilized as reference methods. To compare MRI parameters with reference parameters (equilibrium and dynamic moduli, proteoglycan content, collagen fiber angle and -anisotropy), depth-wise profiles of MRI parameters were acquired at the biomechanical testing locations. Partial least squares regression (PLSR) and Spearman's rank correlation were utilized in data analysis. RESULTS: PLSR indicated a moderate-to-strong correlation (ρ = 0.49-0.66) and a moderate correlation (ρ = 0.41-0.55) between the reference values and T2* relaxation time and QSM profiles, respectively (excluding superficial-only results). PLSR correlations were noticeably higher than direct correlations between bulk MRI and reference parameters. 3-D parametric surface maps revealed spatial variations in the MRI parameters between experimental and control groups. CONCLUSION: Quantitative parameters from 3-D multi-echo gradient echo MRI can be utilized to predict the properties of articular cartilage. With PLSR, especially the T2* relaxation time profile appeared to correlate with the properties of cartilage. Furthermore, the results suggest that degeneration affects the QSM-contrast in the cartilage. However, this change in contrast is not easy to quantify.

Near-infrared spectroscopy enables quantitative evaluation of human cartilage biomechanical properties during arthroscopy.

OBJECTIVE: To investigate the feasibility of near-infrared (NIR) spectroscopy (NIRS) for evaluation of human articular cartilage biomechanical properties during arthroscopy. DESIGN: A novel arthroscopic NIRS probe designed in our research group was utilized by an experienced orthopedic surgeon to measure NIR spectra from articular cartilage of human cadaver knee joints (ex vivo, n = 18) at several measurement locations during an arthroscopic surgery. Osteochondral samples (n = 265) were extracted from the measurement sites for reference analysis. NIR spectra were remeasured in a controlled laboratory environment (in vitro), after which the corresponding cartilage thickness and biomechanical properties were determined. Hybrid multivariate regression models based on principal component analysis and linear mixed effects modeling (PCA-LME) were utilized to relate cartilage in vitro spectra and biomechanical properties, as well as to account for the spatial dependency. Additionally, a k-nearest neighbors (kNN) classifier was employed to reject outlying ex vivo NIR spectra resulting from a non-optimal probe-cartilage contact. Model performance was evaluated for both in vitro and ex vivo NIR spectra via Spearman's rank correlation (ρ) and the ratio of performance to interquartile range (RPIQ). RESULTS: Regression models accurately predicted cartilage thickness and biomechanical properties from in vitro NIR spectra (Model: 0.77 ≤ ρ ≤ 0.87, 2.03 ≤ RPIQ ≤ 3.0; Validation: 0.74 ≤ ρ ≤ 0.84, 1.87 ≤ RPIQ ≤ 2.90). When predicting cartilage properties from ex vivo NIR spectra (0.33 ≤ ρ ≤ 0.57 and 1.02 ≤ RPIQ ≤ 2.14), a kNN classifier enhanced the accuracy of predictions (0.52 ≤ ρ ≤ 0.87 and 1.06 ≤ RPIQ ≤ 1.88). CONCLUSION: Arthroscopic NIRS could substantially enhance identification of damaged cartilage by enabling quantitative evaluation of cartilage biomechanical properties. The results demonstrate the capacity of NIRS in clinical applications.

Tissue viscoelasticity is related to tissue composition but may not fully predict the apparent-level viscoelasticity in human trabecular bone - An experimental and finite element study.

Trabecular bone is viscoelastic under dynamic loading. However, it is unclear how tissue viscoelasticity controls viscoelasticity at the apparent-level. In this study, viscoelasticity of cylindrical human trabecular bone samples (n=11, male, age 18-78 years) from 11 proximal femurs were characterized using dynamic and stress-relaxation testing at the apparent-level and with creep nanoindentation at the tissue-level. In addition, bone tissue elasticity was determined using scanning acoustic microscope (SAM). Tissue composition and collagen crosslinks were assessed using Raman micro-spectroscopy and high performance liquid chromatography (HPLC), respectively. Values of material parameters were obtained from finite element (FE) models by optimizing tissue-level creep and apparent-level stress-relaxation to experimental nanoindentation and unconfined compression testing values, respectively, utilizing the second order Prony series to depict viscoelasticity. FE simulations showed that tissue-level equilibrium elastic modulus (Eeq) increased with increasing crystallinity (r=0.730, p=.011) while at the apparent-level it increased with increasing hydroxylysyl pyridinoline content (r=0.718, p=.019). In addition, the normalized shear modulus g1 (r=-0.780, p=.005) decreased with increasing collagen ratio (amide III/CH2) at the tissue-level, but increased (r=0.696, p=.025) with increasing collagen ratio at the apparent-level. No significant relations were found between the measured or simulated viscoelastic parameters at the tissue- and apparent-levels nor were the parameters related to tissue elasticity determined with SAM. However, only Eeq, g2 and relaxation time τ1 from simulated viscoelastic values were statistically different between tissue- and apparent-levels (p<.01). These findings indicate that bone tissue viscoelasticity is affected by tissue composition but may not fully predict the macroscale viscoelasticity in human trabecular bone.

Multimodality scoring of chondral injuries in the equine fetlock joint ex vivo.

OBJECTIVE: We investigate the potential of a prototype multimodality arthroscope, combining ultrasound, optical coherence tomography (OCT) and arthroscopic indentation device, for assessing cartilage lesions, and compare the reliability of this approach with conventional arthroscopic scoring ex vivo. DESIGN: Areas of interest (AIs, N = 43) were selected from equine fetlock joints (N = 5). Blind-coded AIs were independently scored by two equine surgeons employing International Cartilage Repair Society (ICRS) scoring system via conventional arthroscope and multimodality arthroscope, in which high-frequency ultrasound and OCT catheters were attached to an arthroscopic indentation device. In addition, cartilage stiffness was measured with the indentation device, and lesions in OCT images scored using custom-made automated software. Measurements and scorings were performed twice in two separate rounds. Finally, the scores were compared to histological ICRS scores. RESULTS: OCT and arthroscopic examinations showed the highest average agreements (55.2%) between the scoring by surgeons and histology scores, whereas ultrasound had the lowest (50.6%). Average intraobserver agreements of surgeons and interobserver agreements between rounds were, respectively, for conventional arthroscope (68.6%, 69.8%), ultrasound (68.6%, 68.6%), OCT (65.1%, 61.7%) and automated software (65.1%, 59.3%). CONCLUSIONS: OCT imaging supplemented with the automated software provided the most reliable lesion scoring. However, limited penetration depth of light limits the clinical potential of OCT in assessing human cartilage thickness; thus, the combination of OCT and ultrasound could be optimal for reliable diagnostics. Present findings suggest imaging and quantitatively analyzing the entire articular surface to eliminate surgeon-related variation in the selection of the most severe lesion to be scored.

Semi-automated International Cartilage Repair Society scoring of equine articular cartilage lesions in optical coherence tomography images.

BACKGROUND: Arthroscopic optical coherence tomography (OCT) is a promising tool for the detailed evaluation of articular cartilage injuries. However, OCT-based articular cartilage scoring still relies on the operator's visual estimation. OBJECTIVES: To test the hypothesis that semi-automated International Cartilage Repair Society (ICRS) scoring of chondral lesions seen in OCT images could enhance intra- and interobserver agreement of scoring and its accuracy. STUDY DESIGN: Validation study using equine cadaver tissue. METHODS: Osteochondral samples (n = 99) were prepared from 18 equine metacarpophalangeal joints and imaged using OCT. Custom-made software was developed for semi-automated ICRS scoring of cartilage lesions on OCT images. Scoring was performed visually and semi-automatically by five observers, and levels of inter- and intraobserver agreement were calculated. Subsequently, OCT-based scores were compared with ICRS scores based on light microscopy images of the histological sections of matching locations (n = 82). RESULTS: When semi-automated scoring of the OCT images was performed by multiple observers, mean levels of intraobserver and interobserver agreement were higher than those achieved with visual OCT scoring (83% vs. 77% and 74% vs. 33%, respectively). Histology-based scores from matching regions of interest agreed better with visual OCT-based scoring than with semi-automated OCT scoring; however, the accuracy of the software was improved by optimising the threshold combinations used to determine the ICRS score. MAIN LIMITATIONS: Images were obtained from cadavers. CONCLUSIONS: Semi-automated scoring software improved the reproducibility of ICRS scoring of chondral lesions in OCT images and made scoring less observer-dependent. The image analysis and segmentation techniques adopted in this study warrant further optimisation to achieve better accuracy with semi-automated ICRS scoring. In addition, studies on in vivo applications are required.

Solute Transport of Negatively Charged Contrast Agents Across Articular Surface of Injured Cartilage.

Solute transport through the extracellular matrix (ECM) is crucial to chondrocyte metabolism. Cartilage injury affects solute transport in cartilage due to alterations in ECM structure and solute-matrix interactions. Therefore, cartilage injury may be detected by using contrast agent-based clinical imaging. In the present study, effects of mechanical injury on transport of negatively charged contrast agents in cartilage were characterized. Using cartilage plugs injured by mechanical compression protocol, effective partition coefficients and diffusion fluxes of iodine- and gadolinium-based contrast agents were measured using high resolution microCT imaging. For all contrast agents studied, effective diffusion fluxes increased significantly, particularly at early times during the diffusion process (38 and 33% increase after 4 min, P < 0.05 for iodine and Gd-DTPA; and 76% increase after 10 min for diatrizoate, P < 0.05). Effective partition coefficients were unaffected in mechanically injured cartilage. Mechanical injury reduced PG content and collagen integrity in cartilage superficial zone. This study suggests that alterations in contrast agent diffusion flux, a non-equilibrium transport parameter, provides a more sensitive indicator for assessment of cartilage matrix integrity than partition coefficient and the equilibrium distribution of solute. These findings may help in developing clinical methods of contrast agent-based imaging to detect cartilage injury.

Optimal graft stiffness and pre-strain restore normal joint motion and cartilage responses in ACL reconstructed knee.

Anterior cruciate ligament (ACL) rupture leads to abnormal loading of the knee joint and increases the risk of osteoarthritis. It is unclear how different ACL reconstruction techniques affect knee joint motion and mechanics. As the in vivo measurement of knee joint loading is not possible, we used finite element analysis to assess the outcome of ACL reconstruction techniques. Effects of different ACL reconstruction techniques on knee joint mechanics were studied using six models during gait; with 1) healthy ACL, 2) ACL rupture, 3) single bundle ACL reconstruction, 4) double bundle ACL reconstruction, 5) weakened (softer) single bundle reconstruction and 6) single bundle reconstruction with less pre-strain. Early in the gait, the ACL rupture caused substantially increased tibial translation in the anterior direction as well as a smaller but increased lateral translation and internal tibial rotation. ACL rupture substantially reduced average stresses and strains, while local peak stresses and strains could be either increased or decreased. Single bundle and double bundle reconstructions restored joint motion close to normal levels. However, cartilage strains and stresses were elevated during the entire gait cycle. Models with modulated graft stiffness and pre-strain restored the joint motion and cartilage stresses and strains close to the normal, healthy levels. Results suggest that rather than the choice of reconstruction technique, stiffness and pre-strain of the ACL reconstruction affect the motion and mechanics of the operated knee. We suggest that an optimal choice of graft properties might help restore normal knee joint function and cartilage responses, thus, minimizing the risk of osteoarthritis.

Effect of collagen cross-linking on quantitative MRI parameters of articular cartilage.

OBJECTIVE: To investigate the sensitivity of quantitative magnetic resonance imaging (MRI) parameters to increase of collagen cross-linking in articular cartilage, a factor possibly contributing to the aging-related development of osteoarthritis (OA). The issue has not been widely studied although collagen cross-links may significantly affect the evaluation of cartilage imaging outcome. DESIGN: Osteochondral samples (n = 14) were prepared from seven bovine patellae. To induce cross-linking, seven samples were incubated in threose while the other seven served as non-treated controls. The specimens were scanned at 9.4 T for T1, T1Gd (dGEMRIC), T2, adiabatic and continuous wave (CW) T1ρ, adiabatic T2ρ and T1sat relaxation times. Specimens from adjacent tissue were identically treated and used for reference to determine biomechanical properties, collagen, proteoglycan and cross-link contents, fixed charge density (FCD), collagen fibril anisotropy and water concentration of cartilage. RESULTS: In the threose-treated sample group, cross-links (pentosidine, lysyl pyridinoline (LP)), FCD and equilibrium modulus were significantly (P < 0.05) higher as compared to the non-treated group. Threose treatment resulted in significantly greater T1Gd relaxation time constant (+26%, P < 0.05), although proteoglycan content was not altered. Adiabatic and CW-T1ρ were also significantly increased (+16%, +28%, P < 0.05) while pre-contrast T1 was significantly decreased (-10%, P < 0.05) in the threose group. T2, T2ρ and T1sat did not change significantly. CONCLUSION: Threose treatment induced collagen cross-linking and changes in the properties of articular cartilage, which were detected by T1, T1Gd and T1ρ relaxation time constants. Cross-linking should be considered especially when interpreting the outcome of contrast-enhanced MRI in aging populations.

Importance of Patella, Quadriceps Forces, and Depthwise Cartilage Structure on Knee Joint Motion and Cartilage Response During Gait.

In finite-element (FE) models of the knee joint, patella is often omitted. We investigated the importance of patella and quadriceps forces on the knee joint motion by creating an FE model of the subject's knee. In addition, depthwise strains and stresses in patellar cartilage with different tissue properties were determined. An FE model was created from subject's magnetic resonance images. Knee rotations, moments, and translational forces during gait were recorded in a motion laboratory and used as an input for the model. Three material models were implemented into the patellar cartilage: (1) homogeneous model, (2) inhomogeneous (arcadelike fibrils), and (3) random fibrils at the superficial zone, mimicking early stages of osteoarthritis (OA). Implementation of patella and quadriceps forces into the model substantially reduced the internal-external femoral rotations (versus without patella). The simulated rotations in the model with the patella matched the measured rotations at its best. In the inhomogeneous model, maximum principal stresses increased substantially in the middle zone of the cartilage. The early OA model showed increased compressive strains in the superficial and middle zones of the cartilage and decreased stresses and fibril strains especially in the middle zone. The results suggest that patella and quadriceps forces should be included in moment- and force-driven FE knee joint models. The results indicate that the middle zone has a major role in resisting shear forces in the patellar cartilage. Also, early degenerative changes in the collagen network substantially affect the cartilage depthwise response in the patella during walking.

Effect of porosity, tissue density, and mechanical properties on radial sound speed in human cortical bone.

PURPOSE: The purpose of this study was to investigate the effect of simultaneous changes in cortical porosity, tissue mineral density, and elastic properties on radial speed of sound (SOS) in cortical bone. The authors applied quantitative pulse-echo (PE) ultrasound techniques that hold much potential especially for screening of osteoporosis at primary healthcare facilities. Currently, most PE measurements of cortical thickness, a well-known indicator of fracture risk, use a predefined estimate for SOS in bone to calculate thickness. Due to variation of cortical bone porosity, the use of a constant SOS value propagates to an unknown error in cortical thickness assessment by PE ultrasound. METHODS: The authors conducted 2.25 and 5.00 MHz focused PE ultrasound time of flight measurements on femoral diaphyses of 18 cadavers in vitro. Cortical porosities of the samples were determined using microcomputed tomography and related to SOS in the samples. Additionally, the effect of cortical bone porosity and mechanical properties of the calcified matrix on SOS was investigated using numerical finite difference time domain simulations. RESULTS: Both experimental measurements and simulations demonstrated significant negative correlation between radial SOS and cortical porosity (R(2) ≥ 0.493, p < 0.01 and R(2) ≥ 0.989, p < 0.01, respectively). When a constant SOS was assumed for cortical bone, the error due to variation of cortical bone porosity (4.9%-16.4%) was about 6% in the cortical thickness assessment in vitro. CONCLUSIONS: Use of a predefined, constant value for radial SOS in cortical bone, i.e., neglecting the effect of measured variation in cortical porosity, propagated to an error of 6% in cortical thickness. This error can be critical as characteristic cortical thinning of 1.10% ± 1.06% per yr decreases bending strength of the distal radius and results in increased fragility in postmenopausal women. Provided that the cortical porosity can be estimated in vivo, the relationship between radial SOS and cortical porosity can be utilized and a porosity based radial SOS estimate could be implemented to determine cortical thickness. This would constitute a step toward individualized quantitative ultrasound diagnostics of osteoporosis.

Effect of bone inhomogeneity on tibiofemoral contact mechanics during physiological loading.

It is not known how inhomogeneous mechanical properties of bone affect contact mechanics and cartilage response during physiological loading of the knee joint. In this study, a finite element model of a cadaver knee joint was constructed based on quantitative computed tomography (QCT). The mechanical properties of bone were altered and their effect on tibiofemoral contact mechanics and cartilage stresses, strains and pore pressures were evaluated during the first 20% of stance. For this purpose, models with rigid, homogeneous and inhomogeneous bones were created. When bone was modeled to be rigid, the resulting contact pressures were substantially higher in the medial side of the joint, as compared to the non-rigid bones. Similar changes were revealed also in stresses, strains and pore pressures throughout the cartilage depth at the cartilage-cartilage contact area. Furthermore, the mechanical response of medial tibial cartilage was found to be highly dependent on the bone properties. When Young׳s modulus in the model with homogeneous bone was 5GPa, cartilage mechanical response approached to that of the model with inhomogeneous bone. Finally, when the apparent bone mineral densities were decreased globally in the inhomogeneous bone, stresses, strains and pore pressures were decreased at all layers of medial tibial cartilage. Similar changes were observed also in cartilage-cartilage contact area of the lateral compartment but with a lesser extent. These results indicate that during physiological loading Young׳s modulus of bone has a substantial influence on cartilage stresses and strains, especially in the medial compartment.