| 1. |
- Prittinen, Juha, 1989-, et al.
(författare)
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Effect of gravitational force on the development of articular neocartilage with bovine primary chondrocytes
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- A lot of effort has been invested into understanding how to assemble cartilage tissue in vitro. Various scaffold types have been used in order to manufacture cartilage tissue with native-like biological properties, while cell-based self-assembly of cartilage without a scaffold material is another strategy utilized. Mechanical forces have also been exploited in the manufacturing process. In this study, we used bovine primary chondrocytes to self-assemble a scaffold-free constructs to investigate whether mechanical loading by gravitational force would be useful in manufacturing cartilage tissue in vitro. Six million chondrocytes were laid on top of defatted bone disks placed inside agarose well in 50 ml culture tubes. The constructs were centrifuged once or three times a day for 15 min at gravitational force of 770 x g for one, two and four weeks. Control samples were cultured under the same conditions without exposure to centrifugation. The samples were analysed by (immuno)histochemistry, Fourier transform infrared imaging, micro-computed tomography, biochemical and gene expression analyses. Biomechanical testing was also performed. Macroscopically, the centrifuged tissues had a more even surface covering a larger area of the bone disk. Fourier transform infrared imaging analysis indicated higher concentration of collagen in the top and bottom edges of the centrifuged samples. Glycosaminoglycan contents increased along the culture, while collagen content appeared to remain at a rather constant level. Aggrecan and procollagen α1(II) gene expression levels had no significant differences, while procollagen α2(I) levels were increased significantly. Biomechanical analyses did not reveal remarkable changes. In conclusion, both of the centrifugation regimes lead to a more uniform tissue constructs, while the biological properties of the native tissue could not be obtained.
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| 2. |
- Bayramoglu, Neslihan, et al.
(författare)
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Deep Learning for Predicting Progression of Patellofemoral Osteoarthritis Based on Lateral Knee Radiographs, Demographic Data and Symptomatic Assessments
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Ingår i: Methods of Information in Medicine. - 0026-1270.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: In this study, we propose a novel framework that utilizes deep learning and attention mechanisms to predict the radiographic progression of patellofemoral osteoarthritis (PFOA) over a period of seven years. Design: This study included subjects (1832 subjects, 3276 knees) from the baseline of the Multicenter Osteoarthritis Study (MOST). Patellofemoral joint regions-of interest were identified using an automated landmark detection tool (BoneFinder) on lateral knee X-rays. An end-to-end deep learning method was developed for predicting PFOA progression based on imaging data in a 5-fold cross-validation setting. To evaluate the performance of the models, a set of baselines based on known risk factors were developed and analyzed using gradient boosting machine (GBM). Risk factors included age, sex, BMI and WOMAC score, and the radiographic osteoarthritis stage of the tibiofemoral joint (KL score). Finally, to increase predictive power, we trained an ensemble model using both imaging and clinical data. Results: Among the individual models, the performance of our deep convolutional neural network attention model achieved the best performance with an AUC of 0.856 and AP of 0.431; slightly outperforming the deep learning approach without attention (AUC=0.832, AP= 0.4) and the best performing reference GBM model (AUC=0.767, AP= 0.334). The inclusion of imaging data and clinical variables in an ensemble model allowed statistically more powerful prediction of PFOA progression (AUC = 0.865, AP=0.447), although the clinical significance of this minor performance gain remains unknown. The spatial attention module improved the predictive performance of the backbone model, and the visual interpretation of attention maps focused on the joint space and the regions where osteophytes typically occur. Conclusion: This study demonstrated the potential of machine learning models to predict the progression of PFOA using imaging and clinical variables. These models could be used to identify patients who are at high risk of progression and prioritize them for new treatments. However, even though the accuracy of the models were excellent in this study using the MOST dataset, they should be still validated using external patient cohorts in the future.
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| 3. |
- Ebrahimi, Mohammadhossein, et al.
(författare)
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Associations of human femoral condyle cartilage structure and composition with viscoelastic and constituent-specific material properties at different stages of osteoarthritis
- 2022
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Ingår i: Journal of Biomechanics. - : Elsevier BV. - 0021-9290. ; 145
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Tidskriftsartikel (refereegranskat)abstract
- The relationships between structure and function in human knee femoral cartilage are not well-known at different stages of osteoarthritis. Thus, our aim was to characterize the depth-dependent composition and structure (proteoglycan content, collagen network organization and collagen content) of normal and osteoarthritic human femoral condyle cartilage (n = 47) and relate them to their viscoelastic and constituent-specific mechanical properties that are obtained through dynamic sinusoidal testing and fibril-reinforced poroelastic material modeling of stress-relaxation testing, respectively. We characterized the proteoglycan content using digital densitometry, collagen network organization (orientation angle and anisotropy) using polarized light microscopy and collagen content using Fourier transform infrared spectroscopy. In the superficial cartilage (0–10 % of thickness), the collagen network disorganization and proteoglycan loss were associated with the smaller initial fibril network modulus - a parameter representing the pretension of the collagen network. Furthermore, the proteoglycan loss was associated with the greater strain-dependent fibril network modulus - a measure of nonlinear mechanical behavior. The proteoglycan loss was also associated with greater cartilage viscosity at a low loading frequency (0.005 Hz), while the collagen network disorganization was associated with greater cartilage viscosity at a high loading frequency (1 Hz). Our results suggest that proteoglycan loss and collagen network disorganization reduce the pretension of the collagen network while proteoglycan degradation also increases the nonlinear mechanical behavior of the collagen network. Further, the results also highlight that proteoglycan loss and collagen disorganization increase the viscosity of femoral cartilage, but their contribution to increased viscosity occurs in completely different loading frequencies.
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| 4. |
- Ebrahimi, Mohammadhossein, et al.
(författare)
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Elastic, Dynamic Viscoelastic and Model-Derived Fibril-Reinforced Poroelastic Mechanical Properties of Normal and Osteoarthritic Human Femoral Condyle Cartilage
- 2021
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Ingår i: Annals of Biomedical Engineering. - : Springer Science and Business Media LLC. - 0090-6964 .- 1573-9686. ; 49:9, s. 2622-2634
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Tidskriftsartikel (refereegranskat)abstract
- Osteoarthritis (OA) degrades articular cartilage and weakens its function. Modern fibril-reinforced poroelastic (FRPE) computational models can distinguish the mechanical properties of main cartilage constituents, namely collagen, proteoglycans, and fluid, thus, they can precisely characterize the complex mechanical behavior of the tissue. However, these properties are not known for human femoral condyle cartilage. Therefore, we aimed to characterize them from human subjects undergoing knee replacement and from deceased donors without known OA. Multi-step stress-relaxation measurements coupled with sample-specific finite element analyses were conducted to obtain the FRPE material properties. Samples were graded using OARSI scoring to determine the severity of histopathological cartilage degradation. The results suggest that alterations in the FRPE properties are not evident in the moderate stages of cartilage degradation (OARSI 2-3) as compared with normal tissue (OARSI 0-1). Drastic deterioration of the FRPE properties was observed in severely degraded cartilage (OARSI 4). We also found that the FRPE properties of femoral condyle cartilage related to the collagen network (initial fibril-network modulus) and proteoglycan matrix (non-fibrillar matrix modulus) were greater compared to tibial and patellar cartilage in OA. These findings may inform cartilage tissue-engineering efforts and help to improve the accuracy of cartilage representations in computational knee joint models.
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| 5. |
- Einarsson, Emma, et al.
(författare)
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Relating MR relaxation times of ex vivo meniscus to tissue degeneration through comparison with histopathology
- 2020
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Ingår i: Osteoarthritis and Cartilage Open. - : Elsevier BV. - 2665-9131. ; 2:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: Quantitative magnetic resonance imaging (MRI), e.g. relaxation parameter mapping, may be sensitive to structural and compositional tissue changes, and could potentially be used to non-invasively detect and monitor early meniscus degeneration related to knee osteoarthritis. Objective: To investigate MR relaxation times as potential biomarkers for meniscus degeneration through comparisons with histopathology. Methods: We measured MR relaxation parameters in the posterior horn of 40 menisci (medial and lateral) at a wide range of degenerative stages. T1, T2 and T2∗ were mapped using standard and ultrashort echo time sequences at 9.4 T and compared to gold standard histology using Pauli's histopathological scoring system, including assessment of surface integrity, collagen organization, cellularity and Safranin-O staining. Results: All three relaxation times increased with total Pauli score (mean difference per score (95% CI) for T2∗: 0.62 (0.37, 0.86), T2: 0.83 (0.53, 1.1) and T1: 24.7 (16.5, 32.8) ms/score). Clear associations were seen with scores of surface integrity (mean difference per score for T2∗: 3.0 (1.8, 4.2), T2: 4.0 (2.5, 5.5) and T1: 116 (75.6, 156) ms/score) and collagen organization (mean difference between highest and lowest score for T2∗: 5.3 (1.6, 8.9), T2: 6.1 (1.7, 11) and T1: 204 (75.9, 332) ms). The results were less clear for the remaining histopathological measures. Conclusions: MR relaxation times T1, T2 and T2∗ of ex vivo human menisci are associated with histologically verified degenerative processes, in particular related to surface integrity and collagen organization. If confirmed in vivo, MR relaxation times may thus be potential biomarkers for meniscus degeneration.
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| 6. |
- Finnilä, Mikko A J, et al.
(författare)
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Mineral Crystal Thickness in Calcified Cartilage and Subchondral Bone in Healthy and Osteoarthritic Human Knees
- 2022
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 37:9, s. 1700-1710
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Tidskriftsartikel (refereegranskat)abstract
- Osteoarthritis (OA) is the most common joint disease, where articular cartilage degradation is often accompanied with sclerosis of the subchondral bone. However, the association between OA and tissue mineralization at the nanostructural level is currently not understood. In particular, it is technically challenging to study calcified cartilage, where relevant but poorly understood pathological processes such as tidemark multiplication and advancement occur. Here, we used state-of-the-art microfocus small-angle X-ray scattering with a 5-μm spatial resolution to determine the size and organization of the mineral crystals at the nanostructural level in human subchondral bone and calcified cartilage. Specimens with a wide spectrum of OA severities were acquired from both medial and lateral compartments of medial compartment knee OA patients (n = 15) and cadaver knees (n = 10). Opposing the common notion, we found that calcified cartilage has thicker and more mutually aligned mineral crystals than adjoining bone. In addition, we, for the first time, identified a well-defined layer of calcified cartilage associated with pathological tidemark multiplication, containing 0.32 nm thicker crystals compared to the rest of calcified cartilage. Finally, we found 0.2 nm thicker mineral crystals in both tissues of the lateral compartment in OA compared with healthy knees, indicating a loading-related disease process because the lateral compartment is typically less loaded in medial compartment knee OA. In summary, we report novel changes in mineral crystal thickness during OA. Our data suggest that unloading in the knee might be involved with the growth of mineral crystals, which is especially evident in the calcified cartilage.
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| 7. |
- Honkanen, Juuso, et al.
(författare)
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Cationic contrast agent diffusion differs between cartilage and meniscus
- 2016
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Ingår i: Annals of Biomedical Engineering. - : Springer. - 0090-6964 .- 1573-9686. ; 44:10, s. 2913-2921
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Tidskriftsartikel (refereegranskat)abstract
- Contrast enhanced computed tomography (CECT) is a non-destructive imaging technique used for the assessment of composition and structure of articular cartilage and meniscus. Due to structural and compositional differences between these tissues, diffusion and distribution of contrast agents may differ in cartilage and meniscus. The aim of this study is to determine the diffusion kinematics of a novel iodine based cationic contrast agent (CA(2+)) in cartilage and meniscus. Cylindrical cartilage and meniscus samples (d = 6 mm, h ≈ 2 mm) were harvested from healthy bovine knee joints (n = 10), immersed in isotonic cationic contrast agent (20 mgI/mL), and imaged using a micro-CT scanner at 26 time points up to 48 h. Subsequently, normalized X-ray attenuation and contrast agent diffusion flux, as well as water, collagen and proteoglycan (PG) contents in the tissues were determined. The contrast agent distributions within cartilage and meniscus were different. In addition, the normalized attenuation and diffusion flux were higher (p < 0.05) in cartilage. Based on these results, diffusion kinematics vary between cartilage and meniscus. These tissue specific variations can affect the interpretation of CECT images and should be considered when cartilage and meniscus are assessed simultaneously.
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| 8. |
- Karhula, Sakari, et al.
(författare)
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Effects of articular cartilage constituents on phosphotungstic acid enhanced micro-computed tomography
- 2017
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Contrast-enhanced micro-computed tomography (CEμCT) with phosphotungstic acid (PTA) has shown potential for detecting collagen distribution of articular cartilage. However, the selectivity of the PTA staining to articular cartilage constituents remains to be elucidated. The aim of this study was to investigate the dependence of PTA for the collagen content in bovine articular cartilage. Adjacent bovine articular cartilage samples were treated with chondroitinase ABC and collagenase to degrade the proteoglycan and the collagen constituents in articular cartilage, respectively. Enzymatically degraded samples were compared to the untreated samples using CEμCT and reference methods, such as Fourier-transform infrared imaging. Decrease in the X-ray attenuation of PTA in articular cartilage and collagen content was observed in cartilage depth of 0-13% and deeper in tissue after collagen degradation. Increase in the X-ray attenuation of PTA was observed in the cartilage depth of 13-39% after proteoglycan degradation. The X-ray attenuation of PTA-labelled articular cartilage in CEμCT is associated mainly with collagen content but the proteoglycans have a minor effect on the X-ray attenuation of the PTA-labelled articular cartilage. In conclusion, the PTA labeling provides a feasible CEμCT method for 3D characterization of articular cartilage.
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| 9. |
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| 10. |
- Kobrina, Yevgeniya, et al.
(författare)
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Clustering of infrared spectra reveals histological zones in intact articular cartilage
- 2012
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 20:5, s. 460-468
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Articular cartilage (AC) exhibits specific zonal structure that follows the organization of collagen network and concentration of tissue constituents. The aim of this study was to investigate the potential of unsupervised clustering analysis applied to Fourier transform infrared (FIR) microspectroscopy to detect depth-dependent structural and compositional differences in intact AC. Method: Seven rabbit and eight bovine intact patellae AC samples were imaged using FTIR microspectroscopy and normalized raw spectra were clustered using the fuzzy C-means algorithm. Differences in mean spectra of clusters were investigated by quantitative estimation of collagen and proteoglycan (PG) contents, as well as by careful visual investigation of locations of spectral changes. Results: Clustering revealed the typical layered structure of AC in both species. However, more distinct clusters were found for rabbit samples, whereas bovine AC showed more complex layered structure. In both species, clustering structure corresponded with that in polarized light microscopic (PLM) images; however, some differences were also observed. Spectral differences between clusters were identified at the same spectral locations for both species. Estimated PG/collagen ratio decreased significantly from superficial to middle or deep zones, which might explain the difference in clustering results compared to PLM. Conclusion: FTIR microspectroscopy in combination with cluster analysis allows detailed examination of spatial changes in AC. As far as we know, no previous single technique could reveal a layered structure of AC without any a priori information. (C) 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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| 11. |
- Lammi, Mikko, 1961-, et al.
(författare)
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Undersulfated chondroitin sulfate does not increase in osteoarthritic cartilage.
- 2004
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Ingår i: Journal of Rheumatology. - : Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 31:12, s. 2449-2453
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To test whether there is undersulfation of chondroitin sulfate in osteoarthritic bovine articular cartilage to support the hypothesis that sulfate deficiency is involved with the development of osteoarthritis.METHODS: Cartilage samples from bovine patellae (n = 32) were divided into 3 groups based on their osteoarthritic progression, as assessed by modified Mankin score. Uronic acid contents of the samples were determined. Fragmentation of the proteoglycans due to proteolytic processing was estimated with agarose gel electrophoresis. The molar ratios of chondroitin sulfate isoforms in the extracted proteoglycans were determined with fluorophore-assisted carbohydrate electrophoresis.RESULTS: Loss of proteoglycans and accumulation of tissue water was evident in groups II and III, and progressive OA increased heterogeneity of aggrecan population in groups II and III. Importantly, the molar ratio of nonsulfated disaccharide was decreased in the osteoarthritic articular cartilage.CONCLUSION: The structure of chondroitin sulfate in degenerated bovine cartilage did not support the hypothesis that sulfate depletion is present in osteoarthritic joint.
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| 12. |
- Li, Wenrong, et al.
(författare)
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Comparison of bone texture between normal individuals and patients with Kashin-Beck disease from plain radiographs in knee
- 2018
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- To compare tibial bone texture between Kashin-Beck disease (KBD) patients and normal individuals from plain radiographs using an advanced image analysis. Plain knee radiographs were obtained from KBD patients (n = 49) and age-matched healthy controls (n = 98). KBD were graded with diagnostic criteria WS/T 207-2010. The textural values related to bone structure from medial and lateral tibial subchondral and trabecular bones were evaluated using entropy of Laplacian-based image (ELap), entropy of local binary patterns (ELBP), homogeneity indices (HI) of local angles (HIMean, HIPerp and HIParal), and fractal dimensions from horizontal (FDHor) and vertical (FDVer) structures. KBD patients were shorter in height and lighter in weight, and their tibial width was wider than controls. Anatomical angle of KBD patients showed more genu valgus. Total KBD patients and subgroups had higher ELap, HIMean, HIPerp and HIParal in detected tibial subchondral and trabecular bones than controls, except ELap in lateral subchondral bone. ELBP, FDHor and FDVer from the detected tibial bone in KBD patients and subgroups were lower than controls, except FDVer in lateral trabecular bone. Our results indicate that micro-scale in bone texture in KBD-affected knees can be quantitatively examined from plain radiographs using an advanced image analysis.
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| 13. |
- Nissilä, Tuukka, et al.
(författare)
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Cellulose nanofiber aerogels impregnated with bio-based epoxy using vacuum infusion : Structure, orientation and mechanical properties
- 2018
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Ingår i: Composites Science And Technology. - : Elsevier. - 0266-3538 .- 1879-1050. ; 155, s. 64-71
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Tidskriftsartikel (refereegranskat)abstract
- Cellulose nanofiber aerogels were used as preforms that were impregnated with a bio-epoxy resin via a widely used vacuum infusion process. The simple and straightforward nanocomposite processing approach resulted in an almost 70% improvement in the storage modulus of the polymer with only an 11.7 wt% cellulose nanofiber content. The nanofibers were well dispersed in the polymer matrix and the fiber structures were anisotropically aligned. The impregnation time of the aerogels was also significantly lower than that of the more commonly used nanopapers. It was thus shown that environmentally friendly and mechanically robust nanocomposites could be produced by impregnating cellulose nanofiber aerogels with a thermosetting resin using a processing approach that has potential to be scaled up for commercial use.
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| 14. |
- Orozco, Gustavo A, et al.
(författare)
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Adaptation of Fibril-Reinforced Poroviscoelastic Properties in Rabbit Collateral Ligaments 8 Weeks After Anterior Cruciate Ligament Transection
- 2023
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Ingår i: Annals of Biomedical Engineering. - : Springer Science and Business Media LLC. - 1573-9686 .- 0090-6964. ; 51:4, s. 726-740
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Tidskriftsartikel (refereegranskat)abstract
- Ligaments of the knee provide stability and prevent excessive motions of the joint. Rupture of the anterior cruciate ligament (ACL), a common sports injury, results in an altered loading environment for other tissues in the joint, likely leading to their mechanical adaptation. In the collateral ligaments, the patterns and mechanisms of biomechanical adaptation following ACL transection (ACLT) remain unknown. We aimed to characterize the adaptation of elastic and viscoelastic properties of the lateral and medial collateral ligaments eight weeks after ACLT. Unilateral ACLT was performed in six rabbits, and collateral ligaments were harvested from transected and contralateral knee joints after eight weeks, and from an intact control group (eight knees from four animals). The cross-sectional areas were measured with micro-computed tomography. Stepwise tensile stress-relaxation testing was conducted up to 6% final strain, and the elastic and viscoelastic properties were characterized with a fibril-reinforced poroviscoelastic material model. We found that the cross-sectional area of the collateral ligaments in the ACL transected knees increased, the nonlinear elastic collagen network modulus of the LCL decreased, and the amount of fast relaxation in the MCL decreased. Our results indicate that rupture of the ACL leads to an early adaptation of the elastic and viscoelastic properties of the collagen fibrillar network in the collateral ligaments. These adaptations may be important to consider when evaluating whole knee joint mechanics after ACL rupture, and the results aid in understanding the consequences of ACL rupture on other tissues.
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| 15. |
- Puhakka, Pia, et al.
(författare)
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Dependence of light attenuation and backscattering on collagen concentration and chondrocyte density in agarose scaffolds
- 2014
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Ingår i: Physics in Medicine and Biology. - : Institute of Physics Publishing (IOPP). - 0031-9155 .- 1361-6560. ; 59:21, s. 6537-6548
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Tidskriftsartikel (refereegranskat)abstract
- Optical coherence tomography (OCT) has been applied for high resolution imaging of articular cartilage. However, the contribution of individual structural elements of cartilage on OCT signal has not been thoroughly studied. We hypothesize that both collagen and chondrocytes, essential structural components of cartilage, act as important light scatterers and that variation in their concentrations can be detected by OCT through changes in backscattering and attenuation. To evaluate this hypothesis, we established a controlled model system using agarose scaffolds embedded with variable collagen concentrations and chondrocyte densities. Using OCT, we measured the backscattering coefficient (µb) and total attenuation coefficient (µt) in these scaffolds. Along our hypothesis, light backscattering and attenuation in agarose were dependent on collagen concentration and chondrocyte density. Significant correlations were found between µt and chondrocyte density (ρ = 0.853, p < 0.001) and between µt and collagen concentration (ρ = 0.694, p < 0.001). µb correlated significantly with chondrocyte density (ρ = 0.504, p < 0.001) but not with collagen concentration (ρ = 0.103, p = 0.422) of the scaffold. Thus, quantitation of light backscattering and, especially, attenuation could be valuable when evaluating the integrity of soft tissues, such as articular cartilage with OCT.
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| 16. |
- Rieppo, Lassi, et al.
(författare)
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Infrared microspectroscopic determination of collagen cross-links in articular cartilage
- 2017
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Ingår i: Journal of Biomedical Optics. - : SPIE - International Society for Optical Engineering. - 1083-3668 .- 1560-2281. ; 22:3
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Tidskriftsartikel (refereegranskat)abstract
- Collagen forms an organized network in articular cartilage to give tensile stiffness to the tissue. Due to its long half-life, collagen is susceptible to cross-links caused by advanced glycation end-products. The current standard method for determination of cross-link concentrations in tissues is the destructive high-performance liquid chromatography (HPLC). The aim of this study was to analyze the cross-link concentrations nondestructively from standard unstained histological articular cartilage sections by using Fourier transform infrared (FTIR) microspectroscopy. Half of the bovine articular cartilage samples (n=27) were treated with threose to increase the collagen cross-linking while the other half (n=27) served as a control group. Partial least squares (PLS) regression with variable selection algorithms was used to predict the cross-link concentrations from the measured average FTIR spectra of the samples, and HPLC was used as the reference method for cross-link concentrations. The correlation coefficients between the PLS regression models and the biochemical reference values were r=0.84 (p<0.001), r=0.87 (p<0.001) and r=0.92 (p<0.001) for hydroxylysyl pyridinoline (HP), lysyl pyridinoline (LP), and pentosidine (Pent) cross-links, respectively. The study demonstrated that FTIR microspectroscopy is a feasible method for investigating cross-link concentrations in articular cartilage.
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| 17. |
- Rieppo, Lassi, et al.
(författare)
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Quantitative analysis of spatial proteoglycan content in articular cartilage with Fourier transform infrared imaging spectroscopy : Critical evaluation of analysis methods and specificity of the parameters.
- 2010
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Ingår i: Microscopy research and technique (Print). - : John Wiley & Sons. - 1059-910X .- 1097-0029. ; 73:5, s. 503-512
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the specificity of the current Fourier transform infrared imaging spectroscopy (FT-IRIS) methods for the determination of depthwise proteoglycan (PG) content in articular cartilage (AC). In addition, curve fitting was applied to study whether the specificity of FT-IRIS parameters for PG determination could be improved.METHODS: Two sample groups from the steer AC were prepared for the study (n = 8 samples/group). In the first group, chondroitinase ABC enzyme was used to degrade the PGs from the superficial cartilage, while the samples in the second group served as the controls. Samples were examined with FT-IRIS and analyzed using previously reported direct absorption spectrum techniques and multivariate methods and, in comparison, by curve fitting. Safranin O-stained sections were measured with digital densitometry to obtain a reference for depthwise PG distribution.RESULTS: Carbohydrate region-based absorption spectrum methods showed a statistically weaker correlation with the PG reference distributions than the results of the curve fitting (subpeak located approximately at 1,060 cm(-1)). Furthermore, the shape of the depthwise profiles obtained using the curve fitting was more similar to the reference profiles than with the direct absorption spectrum analysis.CONCLUSIONS: Results suggest that the current FT-IRIS methods for PG analysis lack the specificity for quantitative measurement of PGs in AC. The curve fitting approach demonstrated that it is possible to improve the specificity of the PG analysis. However, the findings of the present study suggest that further development of the FT-IRIS analysis techniques is still needed.
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| 18. |
- Saarakkala, Simo, et al.
(författare)
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Ultrasound indentation of normal and spontaneously degenerated bovine articular cartilage.
- 2003
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Ingår i: Osteoarthritis and Cartilage. - : Saunders Elsevier. - 1063-4584 .- 1522-9653. ; 11:9, s. 697-705
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We have previously developed a handheld ultrasound indentation instrument for the diagnosis of cartilage degeneration. The instrument has been demonstrated to be capable of quantifying mechanical and acoustic properties of enzymatically degraded and normal bovine articular cartilage in vitro and in situ. The aim of this study was to investigate the sensitivity of the instrument to distinguish between normal and spontaneously degenerated (e.g., in osteoarthrosis) articular cartilage in vitro.DESIGN: Thirty articular cartilage samples were prepared from the bovine lateral patellae: 19 patellae with different degenerative stages and 11 patellae with visually normal appearance. Cartilage thickness, stiffness (dynamic modulus) and ultrasound reflection from the cartilage surface were measured with the handheld instrument. Subsequently, biomechanical, histological and biochemical reference measurements were conducted.RESULTS: Reproducibility of the measurements with the ultrasound indentation instrument was good. Standardized coefficient of variation was < or =6.1% for thickness, dynamic modulus and reflection coefficient. Linear correlation between the dynamic modulus, measured with the ultrasound indentation instrument, and the reference dynamic modulus was high (r=0.993, n=30, P<0.05). Ultrasound reflection coefficient, as determined from the cartilage surface, showed high linear correlations (typically r(2)>0.64, n=30, P<0.05) with the cartilage composition and histological or mechanical properties. The instrument was superior compared to visual evaluation in detecting tissue degeneration.CONCLUSION: This study indicates that the ultrasound indentation technique and instrument may significantly improve the early diagnosis of cartilage degeneration. The results revealed that visual evaluation is insensitive for estimating the structural and mechanical properties of articular cartilage at the initial stages of degeneration.
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| 19. |
- Tiulpin, Aleksei, et al.
(författare)
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Predicting total knee arthroplasty from ultrasonography using machine learning
- 2022
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Ingår i: Osteoarthritis and Cartilage Open. - : Elsevier BV. - 2665-9131. ; 4:4, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the value of ultrasonographic data in predicting total knee replacement (TKR).DESIGN: Data from the Musculoskeletal Pain in Ullensaker study (MUST) was linked to the Norwegian Arthroplasty Register to form a 5-7 year prospective cohort study of 630 persons (69% women, mean (SD) age 64 (8.7) years). We examined the predictive power of ultrasound (US) features, i.e. osteophytes, meniscal extrusion, synovitis in the suprapatellar recess, femoral cartilage thickness, and quality for future knee osteoarthritis (OA) surgery. We investigated 4 main settings for multivariate predictive modeling: 1) clinical predictors (age, sex, body mass index, knee injury, familial OA and workload), 2) radiographic data (assessed by the Kellgren Lawrence grade, KL) with clinical predictors, 3) US features and clinical predictors. Finally, we also considered an ensemble of models 2) and 3) and used it as our fifth model. All models were compared using the Average Precision (AP) and the Area Under Receiver Operating Characteristic Curve (AUC) metrics.RESULTS: Clinical predictors yielded AP of 0.11 (95% confidence interval [CI] 0.05-0.23) and AUC of 0.69 (0.58-0.79). Clinical predictors with KL grade yielded AP of 0.20 (0.12-0.33) and AUC of 0.81 (0.67-0.90). The clinical variables with ultrasound yielded AP of 0.17 (0.08-0.30) and AUC of 0.79 (0.69-0.86).CONCLUSION: Ultrasonographic examination of the knee may provide added value to basic clinical and demographic descriptors when predicting TKR. While it does not achieve the same predictive performance as radiography, it can provide additional value to the radiographic examination.
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| 20. |
- Turunen, Siru, et al.
(författare)
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Hypotonic challenge modulates cell volumes differently in the superficial zone of intact articular cartilage and cartilage explant.
- 2012
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Ingår i: Biomechanics and Modeling in Mechanobiology. - : Springer. - 1617-7959 .- 1617-7940. ; 11:5, s. 665-75
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to evaluate the effect of sample preparation on the biomechanical behaviour of chondrocytes. We compared the volumetric and dimensional changes of chondrocytes in the superficial zone (SZ) of intact articular cartilage and cartilage explant before and after a hypotonic challenge. Calcein-AM labelled SZ chondrocytes were imaged with confocal laser scanning microscopy through intact cartilage surfaces and through cut surfaces of cartilage explants. In order to clarify the effect of tissue composition on cell volume changes, Fourier Transform Infrared microspectroscopy was used for estimating the proteoglycan and collagen contents of the samples. In the isotonic medium (300 mOsm), there was a significant difference (p < 0.05) in the SZ cell volumes and aspect ratios between intact cartilage samples and cartilage explants. Changes in cell volumes at both short-term (2 min) and long-term (2 h) time points after the hypotonic challenge (180 mOsm) were significantly different (p < 0.05) between the groups. Further, proteoglycan content was found to correlate significantly (r(2) = 0.63, p < 0.05) with the cell volume changes in cartilage samples with intact surfaces. Collagen content did not correlate with cell volume changes. The results suggest that the biomechanical behaviour of chondrocytes following osmotic challenge is different in intact cartilage and in cartilage explant. This indicates that the mechanobiological responses of cartilage and cell signalling may be significantly dependent on the integrity of the mechanical environment of chondrocytes.
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| 21. |
- Turunen, Siru, et al.
(författare)
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The effect of collagen degradation on chondrocyte volume and morphology in bovine articular cartilage following a hypotonic challenge
- 2013
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Ingår i: Biomechanics and Modeling in Mechanobiology. - : Springer. - 1617-7959 .- 1617-7940. ; 12:3, s. 417-429
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Tidskriftsartikel (refereegranskat)abstract
- Collagen degradation is one of the early signs of osteoarthritis. It is not known how collagen degradation affects chondrocyte volume and morphology. Thus, the aim of this study was to investigate the effect of enzymatically induced collagen degradation on cell volume and shape changes in articular cartilage after a hypotonic challenge. Confocal laser scanning microscopy was used for imaging superficial zone chondrocytes in intact and degraded cartilage exposed to a hypotonic challenge. Fourier transform infrared microspectroscopy, polarized light microscopy, and mechanical testing were used to quantify differences in proteoglycan and collagen content, collagen orientation, and biomechanical properties, respectively, between the intact and degraded cartilage. Collagen content decreased and collagen orientation angle increased significantly (p < 0.05) in the superficial zone cartilage after collagenase treatment, and the instantaneous modulus of the samples was reduced significantly (p < 0.05). Normalized cell volume and height 20 min after the osmotic challenge (with respect to the original volume and height) were significantly (p < 0.001 and p < 0.01, respectively) larger in the intact compared to the degraded cartilage. These findings suggest that the mechanical environment of chondrocytes, specifically collagen content and orientation, affects cell volume and shape changes in the superficial zone articular cartilage when exposed to osmotic loading. This emphasizes the role of collagen in modulating cartilage mechanobiology in diseased tissue.
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| 22. |
- Töyräs, Juha, et al.
(författare)
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Speed of sound in normal and degenerated bovine articular cartilage.
- 2003
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Ingår i: Ultrasound in Medicine and Biology. - : Elsevier. - 0301-5629 .- 1879-291X. ; 29:3, s. 447-454
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Tidskriftsartikel (refereegranskat)abstract
- The unknown and variable speed of sound may impair accuracy of the acoustic measurement of cartilage properties. In this study, relationships between the speed of sound and cartilage composition, mechanical properties and degenerative state were studied in bovine knee and ankle cartilage (n = 62). Further, the effect of speed variation on the determination of cartilage thickness and stiffness with ultrasound (US) indentation was numerically simulated. The speed of sound was significantly (n = 32, p < 0.05) dependent on the cartilage water content (r = -0.800), uronic acid content (per wet weight, r = 0.886) and hydroxyproline content (per wet weight, r = 0.887, n = 28), Young's modulus at equilibrium (r = 0.740), dynamic modulus (r = 0.905), and degenerative state (i.e., Mankin score) (r = -0.727). In addition to cartilage composition, mechanical and acoustic properties varied significantly between different anatomical locations. In US indentation, cartilage is indented with a US transducer. Deformation and thickness of tissue are calculated using a predefined speed of sound and used in determination of dynamic modulus. Based on the simulations, use of the mean speed of sound of 1627 m/s (whole material) induced a maximum error of 7.8% on cartilage thickness and of 6.2% on cartilage dynamic modulus, as determined with the US indentation technique (indenter diameter 3 mm). We believe that these errors are acceptable in clinical US indentation measurements.
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| 23. |
- Virén, Tuomas, et al.
(författare)
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Comparison of ultrasound and optical coherence tomography techniques for evaluation of integrity of spontaneously repaired horse cartilage.
- 2012
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Ingår i: Journal of Medical Engineering & Technology. - : Informa Healthcare. - 0309-1902 .- 1464-522X. ; 36:3, s. 185-192
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to compare sensitivity of ultrasound and optical coherence tomography (OCT) techniques for the evaluation of the integrity of spontaneously repaired horse cartilage. Articular surfaces of horse intercarpal joints, featuring both intact tissue and spontaneously healed chondral or osteochondral defects, were imaged ex vivo with arthroscopic ultrasound and laboratory OCT devices. Quantitative ultrasound (integrated reflection coefficient (IRC), apparent integrated backscattering coefficient (AIB) and ultrasound roughness index (URI)) and optical parameters (optical reflection coefficient (ORC), optical roughness index (ORI) and optical backscattering (OBS)) were determined and compared with histological integrity and mechanical properties of the tissue. Spontaneously healed tissue could be quantitatively discerned from the intact tissue with ultrasound and OCT techniques. Furthermore, several significant correlations (p < 0.05) were detected between ultrasound and OCT parameters. Superior resolution of OCT provided a more accurate measurement of cartilage surface roughness, while the ultrasound backscattering from the inner structures of the cartilage matched better with the histological findings. Since the techniques were found to be complementary to each other, dual modality imaging techniques could provide a useful tool for the arthroscopic evaluation of the integrity of articular cartilage.
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| 24. |
- Virén, Tuomas, et al.
(författare)
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Quantitative evaluation of spontaneously and surgically repaired rabbit articular cartilage using intra-articular ultrasound method in situ.
- 2010
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Ingår i: Ultrasound in Medicine and Biology. - : Elsevier. - 1879-291X .- 0301-5629. ; 36:5, s. 833-839
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Tidskriftsartikel (refereegranskat)abstract
- During the last decade, a major effort has been devoted to developing surgical methods for repairing localized articular cartilage lesions. Despite some promising results no ultimate breakthrough in surgical cartilage repair has been achieved. Improvements in repair techniques would benefit from more sensitive and quantitative methods for long-term follow-up of cartilage healing. In this study, the potential of a new ultrasound technique for detecting the compositional and structural changes in articular cartilage after surgery, using recombinant human type II collagen gel and spontaneous repair was, investigated. Rabbit knee joints containing intact (n = 13) and surgically (n = 8) or spontaneously (n = 5) repaired tissue were imaged in situ at 6 months after the operation using a clinical intravascular high-frequency (40 MHz) ultrasound device. Based on the ultrasound raw data, ultrasound reflection coefficient (R), integrated ultrasound reflection coefficient (IRC), apparent integrated backscattering coefficient (AIB) and ultrasound roughness index (URI) were determined for each sample. URI was significantly higher in both repair groups than in intact cartilage (p < 0.05). The reflection parameters (R and IRC) were significantly lower in surgically repaired cartilage (p < 0.05) than in intact cartilage. Furthermore, AIB was significantly higher in surgically repaired cartilage than in intact tissue (p < 0.05). To conclude, the integrity of the rabbit articular cartilage repair could be quantitatively evaluated with the nondestructive ultrasound approach. In addition, clinically valuable qualitative information on the changes in cartilage integration, structure and composition could be extracted from the ultrasound images. In the present study, the structure and properties of repaired tissue were inferior to native tissue at 6 months after the operation. The applied ultrasound device and probes are FDA approved and, thus, applicable for the quantitative in vivo evaluation of human articular cartilage.
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