Micro-Scale Distribution of CA4+ in Ex vivo Human Articular Cartilage Detected with Contrast-Enhanced Micro-Computed Tomography Imaging
Contrast-enhanced micro-computed tomography (CEμCT) with cationic and anionic contrast agents reveals glycosaminoglycan (GAG) content and distribution in articular cartilage (AC). The advantage of using cationic stains (e.g., CA4+) compared to anionic stains (e.g., Hexabrix®), is that it distributes...
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| Format: | Article |
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Frontiers Media S.A.
2017-08-01
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| Series: | Frontiers in Physics |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fphy.2017.00038/full |
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| author | Sakari S. Karhula Sakari S. Karhula Mikko A. Finnilä Mikko A. Finnilä Mikko A. Finnilä Jonathan D. Freedman Sami Kauppinen Maarit Valkealahti Petri Lehenkari Petri Lehenkari Petri Lehenkari Kenneth P. H. Pritzker Kenneth P. H. Pritzker Heikki J. Nieminen Heikki J. Nieminen Heikki J. Nieminen Brian D. Snyder Mark W. Grinstaff Simo Saarakkala Simo Saarakkala Simo Saarakkala |
| author_facet | Sakari S. Karhula Sakari S. Karhula Mikko A. Finnilä Mikko A. Finnilä Mikko A. Finnilä Jonathan D. Freedman Sami Kauppinen Maarit Valkealahti Petri Lehenkari Petri Lehenkari Petri Lehenkari Kenneth P. H. Pritzker Kenneth P. H. Pritzker Heikki J. Nieminen Heikki J. Nieminen Heikki J. Nieminen Brian D. Snyder Mark W. Grinstaff Simo Saarakkala Simo Saarakkala Simo Saarakkala |
| author_sort | Sakari S. Karhula |
| collection | DOAJ |
| description | Contrast-enhanced micro-computed tomography (CEμCT) with cationic and anionic contrast agents reveals glycosaminoglycan (GAG) content and distribution in articular cartilage (AC). The advantage of using cationic stains (e.g., CA4+) compared to anionic stains (e.g., Hexabrix®), is that it distributes proportionally with GAGs, while anionic stain distribution in AC is inversely proportional to the GAG content. To date, studies using cationic stains have been conducted with sufficient resolution to study its distributions on the macro-scale, but with insufficient resolution to study its distributions on the micro-scale. Therefore, it is not known whether the cationic contrast agents accumulate in extra/pericellular matrix and if they interact with chondrocytes. The insufficient resolution has also prevented to answer the question whether CA4+ accumulation in chondrons could lead to an erroneous quantification of GAG distribution with low-resolution μCT setups. In this study, we use high-resolution μCT to investigate whether CA4+ accumulates in chondrocytes, and further, to determine whether it affects the low-resolution ex vivo μCT studies of CA4+ stained human AC with varying degree of osteoarthritis. Human osteochondral samples were immersed in three different concentrations of CA4+ (3 mgI/ml, 6 mgI/ml, and 24 mgI/ml) and imaged with high-resolution μCT at several timepoints. Different uptake diffusion profiles of CA4+ were observed between the segmented chondrons and the rest of the tissue. While the X-ray -detected CA4+ concentration in chondrons was greater than in the rest of the AC, its contribution to the uptake into the whole tissue was negligible and in line with macro-scale GAG content detected from histology. The efficient uptake of CA4+ into chondrons and surrounding territorial matrix can be explained by the micro-scale distribution of GAG content. CA4+ uptake in chondrons occurred regardless of the progression stage of osteoarthritis in the samples and the relative difference between the interterritorial matrix and segmented chondron area was less than 4%. To conclude, our results suggest that GAG quantification with CEμCT is not affected by the chondron uptake of CA4+. This further confirms the use of CA4+ for macro-scale assessment of GAG throughout the AC, and highlight the capability of studying chondron properties in 3D at the micro scale. |
| first_indexed | 2024-12-21T21:17:21Z |
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| publishDate | 2017-08-01 |
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| series | Frontiers in Physics |
| spelling | doaj.art-a544fb9d2935422aa2271c3acfde2a5c2022-12-21T18:49:58ZengFrontiers Media S.A.Frontiers in Physics2296-424X2017-08-01510.3389/fphy.2017.00038284438Micro-Scale Distribution of CA4+ in Ex vivo Human Articular Cartilage Detected with Contrast-Enhanced Micro-Computed Tomography ImagingSakari S. Karhula0Sakari S. Karhula1Mikko A. Finnilä2Mikko A. Finnilä3Mikko A. Finnilä4Jonathan D. Freedman5Sami Kauppinen6Maarit Valkealahti7Petri Lehenkari8Petri Lehenkari9Petri Lehenkari10Kenneth P. H. Pritzker11Kenneth P. H. Pritzker12Heikki J. Nieminen13Heikki J. Nieminen14Heikki J. Nieminen15Brian D. Snyder16Mark W. Grinstaff17Simo Saarakkala18Simo Saarakkala19Simo Saarakkala20Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of OuluOulu, FinlandInfotech Doctoral Program, University of OuluOulu, FinlandResearch Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of OuluOulu, FinlandDepartment of Applied Physics, University of Eastern FinlandKuopio, FinlandMedical Research Center, University of OuluOulu, FinlandDepartments of Biomedical Engineering and Chemistry, Boston UniversityBoston, MA, United StatesResearch Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of OuluOulu, FinlandDepartment of Surgery and Intensive Care, Oulu University HospitalOulu, FinlandMedical Research Center, University of OuluOulu, FinlandDepartment of Surgery and Intensive Care, Oulu University HospitalOulu, FinlandDepartment of Anatomy and Cell Biology, University of OuluOulu, FinlandDepartment of Laboratory Medicine and Pathobiology, University of TorontoToronto, ON, CanadaMount Sinai HospitalToronto, ON, CanadaResearch Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of OuluOulu, Finland0Department of Physics, University of HelsinkiHelsinki, Finland1Department of Neuroscience and Biomedical Engineering, Aalto UniversityEspoo, Finland2Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical SchoolBoston, MA, United StatesDepartments of Biomedical Engineering and Chemistry, Boston UniversityBoston, MA, United StatesResearch Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of OuluOulu, FinlandMedical Research Center, University of OuluOulu, Finland3Department of Diagnostic Radiology, Oulu University HospitalOulu, FinlandContrast-enhanced micro-computed tomography (CEμCT) with cationic and anionic contrast agents reveals glycosaminoglycan (GAG) content and distribution in articular cartilage (AC). The advantage of using cationic stains (e.g., CA4+) compared to anionic stains (e.g., Hexabrix®), is that it distributes proportionally with GAGs, while anionic stain distribution in AC is inversely proportional to the GAG content. To date, studies using cationic stains have been conducted with sufficient resolution to study its distributions on the macro-scale, but with insufficient resolution to study its distributions on the micro-scale. Therefore, it is not known whether the cationic contrast agents accumulate in extra/pericellular matrix and if they interact with chondrocytes. The insufficient resolution has also prevented to answer the question whether CA4+ accumulation in chondrons could lead to an erroneous quantification of GAG distribution with low-resolution μCT setups. In this study, we use high-resolution μCT to investigate whether CA4+ accumulates in chondrocytes, and further, to determine whether it affects the low-resolution ex vivo μCT studies of CA4+ stained human AC with varying degree of osteoarthritis. Human osteochondral samples were immersed in three different concentrations of CA4+ (3 mgI/ml, 6 mgI/ml, and 24 mgI/ml) and imaged with high-resolution μCT at several timepoints. Different uptake diffusion profiles of CA4+ were observed between the segmented chondrons and the rest of the tissue. While the X-ray -detected CA4+ concentration in chondrons was greater than in the rest of the AC, its contribution to the uptake into the whole tissue was negligible and in line with macro-scale GAG content detected from histology. The efficient uptake of CA4+ into chondrons and surrounding territorial matrix can be explained by the micro-scale distribution of GAG content. CA4+ uptake in chondrons occurred regardless of the progression stage of osteoarthritis in the samples and the relative difference between the interterritorial matrix and segmented chondron area was less than 4%. To conclude, our results suggest that GAG quantification with CEμCT is not affected by the chondron uptake of CA4+. This further confirms the use of CA4+ for macro-scale assessment of GAG throughout the AC, and highlight the capability of studying chondron properties in 3D at the micro scale.http://journal.frontiersin.org/article/10.3389/fphy.2017.00038/fullcontrast agentarticular cartilagechondroncomputed tomographyCA4+ |
| spellingShingle | Sakari S. Karhula Sakari S. Karhula Mikko A. Finnilä Mikko A. Finnilä Mikko A. Finnilä Jonathan D. Freedman Sami Kauppinen Maarit Valkealahti Petri Lehenkari Petri Lehenkari Petri Lehenkari Kenneth P. H. Pritzker Kenneth P. H. Pritzker Heikki J. Nieminen Heikki J. Nieminen Heikki J. Nieminen Brian D. Snyder Mark W. Grinstaff Simo Saarakkala Simo Saarakkala Simo Saarakkala Micro-Scale Distribution of CA4+ in Ex vivo Human Articular Cartilage Detected with Contrast-Enhanced Micro-Computed Tomography Imaging Frontiers in Physics contrast agent articular cartilage chondron computed tomography CA4+ |
| title | Micro-Scale Distribution of CA4+ in Ex vivo Human Articular Cartilage Detected with Contrast-Enhanced Micro-Computed Tomography Imaging |
| title_full | Micro-Scale Distribution of CA4+ in Ex vivo Human Articular Cartilage Detected with Contrast-Enhanced Micro-Computed Tomography Imaging |
| title_fullStr | Micro-Scale Distribution of CA4+ in Ex vivo Human Articular Cartilage Detected with Contrast-Enhanced Micro-Computed Tomography Imaging |
| title_full_unstemmed | Micro-Scale Distribution of CA4+ in Ex vivo Human Articular Cartilage Detected with Contrast-Enhanced Micro-Computed Tomography Imaging |
| title_short | Micro-Scale Distribution of CA4+ in Ex vivo Human Articular Cartilage Detected with Contrast-Enhanced Micro-Computed Tomography Imaging |
| title_sort | micro scale distribution of ca4 in ex vivo human articular cartilage detected with contrast enhanced micro computed tomography imaging |
| topic | contrast agent articular cartilage chondron computed tomography CA4+ |
| url | http://journal.frontiersin.org/article/10.3389/fphy.2017.00038/full |
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