| 1. |
- 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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| 2. |
- Inkinen, Satu, et al.
(författare)
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Collagen and chondrocyte concentrations control ultrasound scattering in agarose scaffolds
- 2014
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Ingår i: Ultrasound in Medicine and Biology. - : Elsevier. - 0301-5629 .- 1879-291X. ; 40:9, s. 2162-2171
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Tidskriftsartikel (refereegranskat)abstract
- Ultrasound imaging has been proposed for diagnostics of osteoarthritis and cartilage injuries in vivo. However, the specific contribution of chondrocytes and collagen to ultrasound scattering in articular cartilage has not been systematically studied. We investigated the role of these tissue structures by measuring ultrasound scattering in agarose scaffolds with varying collagen and chondrocyte concentrations. Ultrasound catheters with center frequencies of 9 MHz (7.1–11.0 MHz, −6 dB) and 40 MHz (30.1–45.3 MHz, −6 dB) were applied using an intravascular ultrasound device. Ultrasound backscattering quantified in a region of interest starting right below sample surface differed significantly (p < 0.05) with the concentrations of collagen and chondrocytes. An ultrasound frequency of 40 MHz, as compared with 9 MHz, was more sensitive to variations in collagen and chondrocyte concentrations. The present findings may improve diagnostic interpretation of arthroscopic ultrasound imaging and provide information necessary for development of models describing ultrasound propagation within cartilage.
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| 3. |
- Kallioniemi, Antti, et al.
(författare)
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Contrast agent enhanced pQCT of articular cartilage.
- 2007
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Ingår i: Physics in Medicine and Biology. - : Institute of Physics Publishing (IOPP). - 0031-9155 .- 1361-6560. ; 52:4, s. 1209-1219
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Tidskriftsartikel (refereegranskat)abstract
- The delayed gadolinium enhanced MRI of cartilage (dGEMRIC) technique is the only non-invasive means to estimate proteoglycan (PG) content in articular cartilage. In dGEMRIC, the anionic paramagnetic contrast agent gadopentetate distributes in inverse relation to negatively charged PGs, leading to a linear relation between T1,Gd and spatial PG content in tissue. In the present study, for the first time, contrast agent enhanced peripheral quantitative computed tomography (pQCT) was applied, analogously to dGEMRIC, for the quantitative detection of spatial PG content in cartilage. The suitability of two anionic radiographic contrast agents, gadopentetate and ioxaglate, to detect enzymatically induced PG depletion in articular cartilage was investigated. First, the interrelationships of x-ray absorption, as measured with pQCT, and the contrast agent solution concentration were investigated. Optimal contrast agent concentrations for the following experiments were selected. Second, diffusion rates for both contrast agents were investigated in intact (n=3) and trypsin-degraded (n=3) bovine patellar cartilage. The contrast agent concentration of the cartilaginous layer was measured prior to and 2-27 h after immersion. Optimal immersion time for the further experiments was selected. Third, the suitability of gadopentetate and ioxaglate enhanced pQCT to detect the enzymatically induced specific PG depletion was investigated by determining the contrast agent concentrations and uronic acid and water contents in digested and intact osteochondral samples (n=16). After trypsin-induced PG loss (-70%, p<0.05) the penetration of gadopentetate and ioxaglate increased (p<0.05) by 34% and 48%, respectively. Gadopentetate and ioxaglate concentrations both showed strong correlation (r=-0.95, r=-0.94, p<0.01, respectively) with the uronic acid content. To conclude, contrast agent enhanced pQCT provides a technique to quantify PG content in normal and experimentally degraded articular cartilage in vitro. As high resolution imaging of e.g. the knee joint is possible with pQCT, the present technique may be further developed for in vivo quantification of PG depletion in osteoarthritic cartilage. However, careful in vitro and in vivo characterization of diffusion mechanics and optimal contrast agent concentrations are needed before diagnostic applications are feasible.
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| 4. |
- Kinnunen, Jussi, et al.
(författare)
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Nondestructive fluorescence-based quantification of threose-induced collagen cross-linking in bovine articular cartilage
- 2012
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Ingår i: Journal of Biomedical Optics. - : SPIE - International Society for Optical Engineering. - 1083-3668 .- 1560-2281. ; 17:9, s. 97003-
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Tidskriftsartikel (refereegranskat)abstract
- Extensive collagen cross-linking affects the mechanical competence of articular cartilage: it can make the cartilage stiffer and more brittle. The concentrations of the best known cross-links, pyridinoline and pentosidine, can be accurately determined by destructive high-performance liquid chromatography (HPLC). We explore a nondestructive evaluation of cross-linking by using the intrinsic fluorescence of the intact cartilage. Articular cartilage samples from bovine knee joints were incubated in threose solution for 40 and 100 h to increase the collagen cross-linking. Control samples without threose were also prepared. Excitation-emission matrices at wavelengths of 220 to 950 nm were acquired from the samples, and the pentosidine and pyridinoline cross-links and the collagen concentrations were determined using HPLC. After the threose treatment, pentosidine and lysyl pyridinole (LP) concentrations increased. The intrinsic fluorescence, excited below 350 nm, decreased and was related to pentosidine [r=−0.90, 240/325nm (excitation/emission)] or LP (r=−0.85, 235/285nm) concentrations. Due to overlapping, the changes in emission could not be linked specifically to the recorded cross-links. However, the fluorescence signal enabled a nondestructive optical estimate of changes in the pentosidine and LP cross-linking of intact articular cartilage.
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| 5. |
- Kopakkala-Tani, Milla, et al.
(författare)
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Ultrasound stimulates proteoglycan synthesis in bovine primary chondrocytes.
- 2006
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Ingår i: Biorheology. - : IOS Press. - 0006-355X .- 1878-5034. ; 43:3-4, s. 271-282
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Tidskriftsartikel (refereegranskat)abstract
- Mechanical forces can stimulate the production of extracellular matrix molecules. We tested the efficacy of ultrasound to increase proteoglycan synthesis in bovine primary chondrocytes. The ultrasound-induced temperature rise was measured and its contribution to the synthesis was investigated using bare heat stimulus. Chondrocytes from five cellular isolations were exposed in triplicate to ultrasound (1 MHz, duty cycle 20%, pulse repetition frequency 1 kHz) at average intensity of 580 mW/cm2 for 10 minutes daily for 1-5 days. Temperature evolution was recorded during the sonication and corresponding temperature history was created using a controllable water bath. This exposure profile was used in 10-minute-long heat treatments of chondrocytes. Heat shock protein 70 (Hsp70) levels after one-time treatment to ultrasound and heat was analyzed by Western blotting, and proteoglycan synthesis was evaluated by 35S-sulfate incorporation. Ultrasound treatment did not induce Hsp70, while heat treatment caused a slight heat stress response. Proteoglycan synthesis was increased approximately 2-fold after 3-4 daily ultrasound stimulations, and remained at that level until day 5 in responsive cell isolates. However, chondrocytes from one donor cell isolation out of five remained non-responsive. Heat treatment alone did not increase proteoglycan synthesis. In conclusion, our study confirms that pulsed ultrasound stimulation can induce proteoglycan synthesis in chondrocytes.
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| 6. |
- Kulmala, Katariina, et al.
(författare)
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Diffusion of ionic and non-ionic contrast agents in articular cartilage with increased cross-linking : contribution of steric and electrostatic effects
- 2013
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Ingår i: Medical Engineering and Physics. - : Elsevier. - 1350-4533 .- 1873-4030. ; 35:10, s. 1415-20
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the effect of threose-induced collagen cross-linking on diffusion of ionic and non-ionic contrast agents in articular cartilage.DESIGN: Osteochondral plugs (Ø=6mm) were prepared from bovine patellae and divided into two groups according to the contrast agent to be used in contrast enhanced computed tomography (CECT) imaging: (I) anionic ioxaglate and (II) non-ionic iodixanol. The groups I and II contained 7 and 6 sample pairs, respectively. One of the paired samples served as a reference while the other was treated with threose to induce collagen cross-linking. The equilibrium partitioning of the contrast agents was imaged after 24h of immersion. Fixed charge density (FCD), water content, contents of proteoglycans, total collagen, hydroxylysyl pyridinoline (HP), lysyl pyridinoline (LP) and pentosidine (Pent) cross-links were determined as a reference.RESULTS: The equilibrium partitioning of ioxaglate (group I) was significantly (p=0.018) lower (-23.4%) in threose-treated than control samples while the equilibrium partitioning of iodixanol (group II) was unaffected by the threose-treatment. FCD in the middle and deep zones of the cartilage (p<0.05) and contents of Pent and LP (p=0.001) increased significantly due to the treatment. However, the proteoglycan concentration was not systematically altered after the treatment. Water content was significantly (-3.5%, p=0.007) lower after the treatment.CONCLUSIONS: Since non-ionic iodixanol showed no changes in partition after cross-linking, in contrast to anionic ioxaglate, we conclude that the cross-linking induced changes in charge distribution have greater effect on diffusion compared to the cross-linking induced changes in steric hindrance.
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| 7. |
- 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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| 8. |
- Lötjönen, Pauno, et al.
(författare)
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Strain-dependent modulation of ultrasound speed in articular cartilage under dynamic compression.
- 2009
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Ingår i: Ultrasound in Medicine and Biology. - : Elsevier. - 1879-291X .- 0301-5629. ; 35:7, s. 1177-1184
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Tidskriftsartikel (refereegranskat)abstract
- Mechanical properties of articular cartilage may be determined by means of mechano-acoustic indentation, a clinically feasible technique for cartilage diagnostics. Unfortunately, ultrasound speed varies in articular cartilage during mechanical compression. This can cause significant errors to the measured mechanical parameters. In this study, the strain-dependent variation in ultrasound speed was investigated during dynamic compression. In addition, we estimated errors that were induced by the variation in ultrasound speed on the mechano-acoustically measured elastic properties of the tissue. Further, we validated a computational method to correct these errors. Bovine patellar cartilage samples (n = 7) were tested under unconfined compression. Strain-dependence of ultrasound speed was determined under different compressive strains using an identical strain-rate. In addition, the modulation of ultrasound speed was simulated using the transient compositional and structural changes derived from fibril-reinforced poroviscoelastic (FRPVE) model. Experimentally, instantaneous compressive strain modulated the ultrasound speed (p < 0.05) significantly. The decrease of ultrasound speed was found to change nonlinearly as a function of strain. Immediately after the ramp loading ultrasound speed was found to be changed -0.94%, -1.49%, -1.84%, -1.87%, -1.89% and -2.15% at the strains of 2.4%, 4.9%, 7.3%, 9.7%, 12.1% and 14.4%, respectively. The numerical simulation revealed that the compression-related decrease in ultrasound speed induces significant errors in the mechano-acoustically determined strain (39.7%) and dynamic modulus (72.1%) at small strains, e.g., at 2.4%. However, at higher strains, e.g., at 14.4%, the errors were smaller, i.e., 12.6% for strain and 14.5% for modulus. After the proposed computational correction, errors related to ultrasound speed were decreased. By using the correction, with e.g., 2.4% strain, errors in strain and modulus were decreased from 39.7% to 7.2% and from 72.1% to 35.3%, respectively. The FRPVE model, addressing the changes in fibril orientation and void ratio during compression, showed discrepancy of less than 1% between the predicted and measured ultrasound speed during the ramp compression.
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| 9. |
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| 10. |
- Ojanen, Xiaowei, et al.
(författare)
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Differences in acoustic impedance of fresh and embedded human trabecular bone samples - Scanning acoustic microscopy and numerical evaluation
- 2016
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Ingår i: Journal of the Acoustical Society of America. - : Acoustical Society of America (ASA). - 0001-4966. ; 140:3, s. 1931-1936
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Tidskriftsartikel (refereegranskat)abstract
- Trabecular bone samples are traditionally embedded and polished for scanning acoustic microscopy (SAM). The effect of sample processing, including dehydration, on the acoustic impedance of bone is unknown. In this study, acoustic impedance of human trabecular bone samples (n = 8) was experimentally assessed before (fresh) and after embedding using SAM and two-dimensional (2-D) finite-difference time domain simulations. Fresh samples were polished with sandpapers of different grit (P1000, P2500, and P4000). Experimental results indicated that acoustic impedance of samples increased significantly after embedding [mean values 3.7 MRayl (fresh), 6.1 MRayl (embedded), p < 0.001]. After polishing with different papers, no significant changes in acoustic impedance were found, even though higher mean values were detected after polishing with finer (P2500 and P4000) papers. A linear correlation (r = 0.854, p < 0.05) was found between the acoustic impedance values of embedded and fresh bone samples polished using P2500 SiC paper. In numerical simulations dehydration increased the acoustic impedance of trabecular bone (38%), whereas changes in surface roughness of bone had a minor effect on the acoustic impedance (-1.56%/0.1 μm). Thereby, the numerical simulations corroborated the experimental findings. In conclusion, acoustic impedance measurement of fresh trabecular bone is possible and may provide realistic material values similar to those of living bone.
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