User menu

Accès à distance ? S'identifier sur le proxy UCLouvain

Contrast-enhanced nanofocus X-ray computed tomography allows virtual three-dimensional histopathology and morphometric analysis of osteoarthritis in small animal models

Primary tabs

download
  • Open access
  • PDF
  • 780.29 K
Kerckhofs, Greet [UCL] Sainz, Julie Marechal, Marina Wevers, Martine Van de Putte, Tom Schrooten, Jan

Objective: One of the early hallmarks of osteoarthritis (OA) is a progressive degeneration of the articular cartilage. Early diagnosis of OA-associated cartilage alterations would be beneficial for disease prevention and control, and for the development of disease-modifying treatments. However, early diagnosis is still hampered by a lack of quantifiable readouts in preclinical models. Design: In this study, we have shown the potency of contrast-enhanced nanofocus x-ray computed tomography (CE-nanoCT) to be used for virtual 3-dimensional (3D) histopathology in established mouse models for OA, and we compared with standard histopathology. Results: We showed the equivalence of CE-nanoCT images to histopathology for the modified Mankin scoring of the cartilage structure and quality. Additionally, a limited set of 3D cartilage characteristics measured by CE-nanoCT image analysis in a user-independent and semiautomatic manner, that is, average and maximum of the noncalcified cartilage thickness distribution and loss in glycosaminoglycans, was shown to be predictive for the cartilage quality and structure as can be evaluated by histopathological scoring through the use of an empirical model. Conclusions: We have shown that CE-nanoCT is a tool that allows virtual histopathology and 3D morphological quantification of multitissue systems, such as the chondro-osseous junction. It provides faster and more quantitative data on cartilage structure and quality compared with standard histopathology while eliminating user bias. CEnanoCT thus should allow capturing subtle differences in cartilage characteristics, carefully mapping OA progression and, ultimately, asses the beneficial changes when testing a candidate disease-modifying treatment.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès libre
Publication date 2014
Language Anglais
Journal information "Cartilage" - Vol. 5, no.1, p. 55-65 (2014)
Peer reviewed yes
Publisher Sage Publications, Inc.
issn 1947-6035
e-issn 1947-6043
Publication status Publié
Affiliations KUL - Division of Skeletal Tissue Engineering
KUL - Skeletal Biology and Engineering Research Center
KUL - Department of Mechanical Engineering
ULg - Biomechanics Research Unit
KUL - Department of Metallurgy and Materials Engineering
Keywords contrast-enhanced nanofocus computed tomography (CE-nanoCT) ; osteoarthritis ; virtual histopathology ; modified Mankin scoring ; 3D cartilage quantification
Links
  1. Bijlsma Johannes WJ, Berenbaum Francis, Lafeber Floris PJG, Osteoarthritis: an update with relevance for clinical practice, 10.1016/s0140-6736(11)60243-2
  2. Gelber Allan C., Joint Injury in Young Adults and Risk for Subsequent Knee and Hip Osteoarthritis, 10.7326/0003-4819-133-5-200009050-00007
  3. Messner Karola, Maletius Wolfgang, The long-term prognosis for severe damage to weight-bearing cartilage in the knee: A 14-year clinical and radiographic follow-up in 28 young athletes, 10.3109/17453679608994664
  4. Maréchal Marina, Van Hauwermeiren Hadewych, Neys Johan, Vanderlinden Gert, Van de Putte Tom, In Vivo Evaluation of Different Surgical Procedures for Autologous Chondrocyte Implantation, 10.1177/1947603512457564
  5. Christiansen B.A., Anderson M.J., Lee C.A., Williams J.C., Yik J.H.N., Haudenschild D.R., Musculoskeletal changes following non-invasive knee injury using a novel mouse model of post-traumatic osteoarthritis, 10.1016/j.joca.2012.04.014
  6. Botter S.M., Glasson S.S., Hopkins B., Clockaerts S., Weinans H., van Leeuwen J.P.T.M., van Osch G.J.V.M., ADAMTS5−/− mice have less subchondral bone changes after induction of osteoarthritis through surgical instability: implications for a link between cartilage and subchondral bone changes, 10.1016/j.joca.2008.09.018
  7. Furman Bridgette D., Strand Jens, Hembree W. Chad, Ward Benjamin D., Guilak Farshid, Olson Steven A., Joint degeneration following closed intraarticular fracture in the mouse knee: A model of posttraumatic arthritis, 10.1002/jor.20331
  8. MANKIN HENRY J., DORFMAN HOWARD, LIPPIELLO LOUIS, ZARINS ANTRA, Biochemical and Metabolic Abnormalities in Articular Cartilage from Osteo-Arthritic Human Hips : II. CORRELATION OF MORPHOLOGY WITH BIOCHEMICAL AND METABOLIC DATA, 10.2106/00004623-197153030-00009
  9. Glasson S.S., Chambers M.G., Van Den Berg W.B., Little C.B., The OARSI histopathology initiative – recommendations for histological assessments of osteoarthritis in the mouse, 10.1016/j.joca.2010.05.025
  10. Xie L., Lin A.S.P., Levenston M.E., Guldberg R.E., Quantitative assessment of articular cartilage morphology via EPIC-μCT, 10.1016/j.joca.2008.07.015
  11. Palmer A. W., Guldberg R. E., Levenston M. E., Analysis of cartilage matrix fixed charge density and three-dimensional morphology via contrast-enhanced microcomputed tomography, 10.1073/pnas.0606406103
  12. Kotwal N., Li J., Sandy J., Plaas A., Sumner D.R., Initial application of EPIC-μCT to assess mouse articular cartilage morphology and composition: effects of aging and treadmill running, 10.1016/j.joca.2012.04.012
  13. Silvast Tuomo S., Jurvelin Jukka S., Tiitu Virpi, Quinn Thomas M., Töyräs Juha, Bath Concentration of Anionic Contrast Agents Does Not Affect Their Diffusion and Distribution in Articular Cartilage In Vitro, 10.1177/1947603512451023
  14. Bansal P.N., Stewart R.C., Entezari V., Snyder B.D., Grinstaff M.W., Contrast agent electrostatic attraction rather than repulsion to glycosaminoglycans affords a greater contrast uptake ratio and improved quantitative CT imaging in cartilage, 10.1016/j.joca.2011.04.004
  15. Xie L., Lin A.S.P., Guldberg R.E., Levenston M.E., Nondestructive assessment of sGAG content and distribution in normal and degraded rat articular cartilage via EPIC-μCT, 10.1016/j.joca.2009.07.014
  16. Kerckhofs G, , Sainz J, Wevers M, Van de Putte T, Schrooten J, Contrast-enhanced nanofocus computed tomography images the cartilage subtissue architecture in three dimensions, 10.22203/ecm.v025a13
  17. Glasson S.S., Blanchet T.J., Morris E.A., The surgical destabilization of the medial meniscus (DMM) model of osteoarthritis in the 129/SvEv mouse, 10.1016/j.joca.2007.03.006
  18. Stewart Rachel C., Bansal Prashant N., Entezari Vahid, Lusic Hrvoje, Nazarian Rosalynn M., Snyder Brian D., Grinstaff Mark W., Contrast-enhanced CT with a High-Affinity Cationic Contrast Agent for Imaging ex Vivo Bovine, Intact ex Vivo Rabbit, and in Vivo Rabbit Cartilage, 10.1148/radiol.12112246
  19. Otsu Nobuyuki, A Threshold Selection Method from Gray-Level Histograms, 10.1109/tsmc.1979.4310076
  20. Hildebrand T., Ruegsegger P., A new method for the model-independent assessment of thickness in three-dimensional images, 10.1046/j.1365-2818.1997.1340694.x
  21. Janes K. A., A Systems Model of Signaling Identifies a Molecular Basis Set for Cytokine-Induced Apoptosis, 10.1126/science.1116598
  22. Miller-Jensen Kathryn, Janes Kevin A., Brugge Joan S., Lauffenburger Douglas A., Common effector processing mediates cell-specific responses to stimuli, 10.1038/nature06001
  23. Platt Manu O., Wilder Catera L., Wells Alan, Griffith Linda G., Lauffenburger Douglas A., Multipathway Kinase Signatures of Multipotent Stromal Cells Are Predictive for Osteogenic Differentiation : Tissue-Specific Stem Cells, 10.1002/stem.215
  24. Janes Kevin A., Kelly Jason R., Gaudet Suzanne, Albeck John G., Sorger Peter K., Lauffenburger Douglas A., Cue-Signal-Response Analysis of TNF-Induced Apoptosis by Partial Least Squares Regression of Dynamic Multivariate Data, 10.1089/cmb.2004.11.544
Bibliographic reference Kerckhofs, Greet ; Sainz, Julie ; Marechal, Marina ; Wevers, Martine ; Van de Putte, Tom ; et. al. Contrast-enhanced nanofocus X-ray computed tomography allows virtual three-dimensional histopathology and morphometric analysis of osteoarthritis in small animal models. In: Cartilage, Vol. 5, no.1, p. 55-65 (2014)
Permanent URL http://hdl.handle.net/2078/194586