Harri T Kokkonen

University of Kuopio, Kuopio, Eastern Finland Province, Finland

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Publications (9)20.87 Total impact

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    ABSTRACT: Contrast enhanced computer tomography (CT) imaging of articular cartilage has been proposed for diagnostics of cartilage degeneration, that is, osteoarthritis. Previous studies also indicate that acute cartilage damage can be detected by measuring diffusion of contrast agent into cartilage using CT. However, currently, there is no reliable method to measure spatial diffusion rates within cartilage tissue, and only average bulk values have been reported. In this paper, we develop a method to determine depthwise diffusivity of contrast agents in cartilage tissue using contrast enhanced CT. The triphasic mechano-electrochemical theory of cartilage is modified to include diffusion of contrast agents. By applying statistical inversion theory and Bayesian approximation error approach, the method allows us to estimate a fixed charge density distribution in the cartilage tissue, an important determinant for mechanical competence of articular cartilage. The method is tested by using a one-dimensional simulation study. Preliminary tests with experimental data on diffusion of anionic iodine contrast agent in bovine articular cartilage indicate that the method can provide realistic estimates for depth dependent fixed charge density. Thereby, the present study can improve our understanding on the feasibility of contrast enhanced CT for cartilage diagnostics. Copyright © 2014 John Wiley & Sons, Ltd.
    International Journal for Numerical Methods in Engineering 05/2014; 98(5). DOI:10.1002/nme.4634 · 1.96 Impact Factor
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    ABSTRACT: The aim of this study was to investigate the feasibility of delayed cone beam (CBCT) arthrography for clinical diagnostics of knee cartilage lesions. Knee joints with cartilage lesions were imaged using native radiography, MRI, and delayed CBCT arthrography techniques in vivo. The joints were imaged three times with CBCT, just before, immediately after (arthrography) and 45 min after the intra-articular injection of contrast agent. The arthrographic images enabled sensitive detection of the cartilage lesions. Use of arthrographic and delayed images together with their subtraction image enabled also detection of cartilage with inferior integrity. The contrast agent partition in intact cartilage (ICRS grade 0) was lower (p < 0.05) than that of cartilage surrounding the ICRS grade I-IV lesions. Delayed CBCT arthrography provides a novel method for diagnostics of cartilage lesions. Potentially, it can also be used in diagnostics of cartilage degeneration. Due to shorter imaging times, higher resolution, and lower costs of CT over MRI, this technique could provide an alternative for diagnostics of knee pathologies. However, for comprehensive evaluation of the clinical potential of the technique a further clinical study with a large pool of patients having a wide range of cartilage pathologies needs to be conducted. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.
    Journal of Orthopaedic Research 11/2013; DOI:10.1002/jor.22521 · 2.88 Impact Factor
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    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.
    Medical Engineering & Physics 04/2013; DOI:10.1016/j.medengphy.2013.03.010 · 1.84 Impact Factor
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    ABSTRACT: Objective: We investigated the feasibility of delayed computed tomography (CT) arthrography for evaluation of human knee cartilage in vivo. Especially, the diffusion of contrast agent out of the joint space and the optimal time points for imaging were determined.
    Cartilage 10/2012; 3(4):334-341. DOI:10.1177/1947603512447300
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    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, 240/325  nm (excitation/emission)] or LP (r=-0.85, 235/285  nm) 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.
    Journal of Biomedical Optics 09/2012; 17(9):97003. DOI:10.1117/1.JBO.17.9.097003 · 2.75 Impact Factor
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    ABSTRACT: Excessive cross-linking of collagen during aging may contribute to degeneration of articular cartilage. Traditionally, the amount of cross-links is derived by using destructive high-performance liquid chromatography (HPLC). However, a sensitive, nondestructive method could help to evaluate tissue integrity, including cross-links. We increased collagen cross-linking in bovine articular cartilage by controlled threose incubation. During the incubation, optical spectral reflectance images of the samples were captured and related to HPLC results using regression analysis. Significant correlations with reflectance and cross-links were observed. When further developed the optical method may enable nondestructive evaluation of cross-links in vivo through a clinical arthroscope.
    Computer-Based Medical Systems (CBMS), 2012 25th International Symposium on; 01/2012
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    ABSTRACT: The effect of threose-induced collagen cross-linking on the mechanical and diffusive properties of cartilage was investigated in vitro. In particular, we investigated the potential of Contrast Enhanced Computed Tomography (CECT) to detect changes in articular cartilage after increased collagen cross-linking, which is an age-related phenomenon. Osteochondral plugs (Ø=6.0 mm, n=28) were prepared from intact bovine patellae (n=7). Two of the four adjacent samples, prepared from each patella, were treated with threose to increase the collagen cross-linking, while the other two specimen served as paired controls. One sample pair was mechanically tested and then mechanically injured using a material testing device. Contrast agent [ioxaglate (Hexabrix™)] diffusion was imaged in the other specimen pair for 25 h using CECT. Water fraction, collagen and proteoglycan content, collagen network architecture and the amount of cross-links [hydroxylysyl pyridinoline (HP), lysyl pyridinoline (LP) and pentosidine (Pent)] of the samples were also determined. Cartilage collagen cross-linking, both Pent and LP, were significantly (P<0.001) increased due to threose treatment. CECT could detect the increased cross-links as the contrast agent penetration and the diffusion flux were significantly (P<0.05) lower in the threose treated than in untreated samples. The equilibrium modulus (+164%, P<0.05) and strain dependent dynamic modulus (+47%, P<0.05) were both significantly greater in the threose treated samples than in reference samples, but there was no association between the initial dynamic modulus and the threose treatment. The water fraction, proteoglycan and collagen contents, as well as collagen architecture, were not significantly altered by the threose treatment. To conclude, the CECT technique was found to be sensitive at detecting changes in cartilage tissue due to increased collagen cross-linking. This is important since increased cross-linking has been proposed to be related to the increased injury susceptibility of tissue.
    Osteoarthritis and Cartilage 07/2011; 19(10):1190-8. DOI:10.1016/j.joca.2011.07.008 · 4.26 Impact Factor
  • H T Kokkonen, J S Jurvelin, V Tiitu, J Töyräs
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    ABSTRACT: Osteoarthritic degeneration may be initiated by mechanical overloading of articular cartilage. Mechanical injury increases the permeability of tissue, thereby probably affecting the diffusion of contrast agents in articular cartilage. We investigated whether it is possible to detect acute cartilage injury by measuring contrast agent diffusion into articular cartilage using contrast enhanced computed tomography (CECT). Osteochondral plugs (Ø=6.0 mm, n=36) were prepared from intact bovine patellae (n=9). Two of the adjacent samples were injured by impact loading, using a drop tower, while the others served as paired controls. The samples were imaged before immersion in contrast agent solution [ioxaglate (Hexabrix™) or sodium iodide (NaI)] and 1, 3, 5, 7, 10, 15, 20 and 25 h after immersion using a MicroCT-instrument. Contrast agent content, diffusion coefficient and diffusion flux were determined for each sample. Already after 1 h the penetration of contrast agents into cartilage was significantly (P<0.05) greater in the injured samples. The diffusion coefficient was not altered by the injury, which suggests that reaching the diffusion equilibrium takes the same time in injured and intact cartilage. However, the diffusion flux of ioxaglate through the articular surface was significantly higher in injured samples at 30-60 min after immersion. To conclude, CECT could diagnose articular cartilage injuries, and determination of the diffusion flux of ioxaglate helped to detect tissue injury without waiting for the diffusion equilibrium. These results are encouraging, however, in vivo application of CECT is challenging and systematic further studies are needed to reveal its clinical potential.
    Osteoarthritis and Cartilage 03/2011; 19(3):295-301. DOI:10.1016/j.joca.2010.12.012 · 4.26 Impact Factor
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    ABSTRACT: Charged contrast agents have been used both in vitro and in vivo for estimation of the fixed charge density (FCD) in articular cartilage. In the present study, the effects of molecular size and charge on the diffusion and equilibrium distribution of several magnetic resonance imaging (MRI) and computed tomography (CT) contrast agents were investigated. Full thickness cartilage disks (Ø = 4.0 mm, n = 64) were prepared from fresh bovine patellae. Contrast agent (gadopentetate: Magnevist((R)), gadodiamide: Omniscan, ioxaglate: Hexabrix or sodium iodide: NaI) diffusion was allowed either through the articular surface or through the deep cartilage. CT imaging of the samples was conducted before contrast agent administration and after 1, 5, 9, 16, 25 and 29 h (and with three samples after 2, 3, 4 and 5 days) diffusion using a clinical peripheral quantitative computed tomography (pQCT) instrument. With all contrast agents, the diffusion through the deep cartilage was slower when compared to the diffusion through the articular surface. With ioxaglate, gadopentetate and gadodiamide it took over 29 h for diffusion to reach the near-equilibrium state. The slow diffusion of the contrast agents raise concerns regarding the validity of techniques for FCD estimation, as these contrast agents may not reach the equilibrium state that is assumed. However, since cartilage composition, i.e. deep versus superficial, had a significant effect on diffusion, imaging of the nonequilibrium diffusion process might enable more accurate assessment of cartilage integrity.
    Physics in Medicine and Biology 11/2009; 54(22):6823-36. DOI:10.1088/0031-9155/54/22/005 · 2.92 Impact Factor

Publication Stats

61 Citations
20.87 Total Impact Points


  • 2009–2014
    • University of Kuopio
      • • Department of Applied Physics
      • • Department of Physics
      Kuopio, Eastern Finland Province, Finland
  • 2011–2013
    • University of Eastern Finland
      • Department of Applied Physics
      Kuopio, Province of Eastern Finland, Finland