Effect of collagen cross-linking on quantitative MRI parameters of articular cartilage

J Rautiainen; M T Nieminen; E-N Salo; H T Kokkonen; S Mangia; S Michaeli; O Gröhn; J S Jurvelin; J Töyräs; M J Nissi

doi:10.1016/j.joca.2016.04.017

Effect of collagen cross-linking on quantitative MRI parameters of articular cartilage

Osteoarthritis Cartilage. 2016 Sep;24(9):1656-64. doi: 10.1016/j.joca.2016.04.017. Epub 2016 Apr 30.

Authors

J Rautiainen¹, M T Nieminen², E-N Salo³, H T Kokkonen⁴, S Mangia⁵, S Michaeli⁶, O Gröhn⁷, J S Jurvelin⁸, J Töyräs⁹, M J Nissi¹⁰

Affiliations

¹ Department of Applied Physics, University of Eastern Finland, Kuopio, Finland; Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland; Medical Research Center Oulu, University of Oulu, Oulu, Finland. Electronic address: jari.rautiainen@uef.fi.
² Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland; Medical Research Center Oulu, University of Oulu, Oulu, Finland; Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland. Electronic address: miika.nieminen@oulu.fi.
³ Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland. Electronic address: elli-noora.salo@iki.fi.
⁴ Diagnostic Imaging Center, Kuopio University Hospital, Kuopio, Finland. Electronic address: harri.t.kokkonen@gmail.com.
⁵ Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, USA. Electronic address: mangia@umn.edu.
⁶ Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, USA. Electronic address: shalom@cmrr.umn.edu.
⁷ Department of Neurobiology, A.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland. Electronic address: olli.grohn@uef.fi.
⁸ Department of Applied Physics, University of Eastern Finland, Kuopio, Finland; Diagnostic Imaging Center, Kuopio University Hospital, Kuopio, Finland. Electronic address: jukka.jurvelin@uef.fi.
⁹ Department of Applied Physics, University of Eastern Finland, Kuopio, Finland; Diagnostic Imaging Center, Kuopio University Hospital, Kuopio, Finland. Electronic address: juha.toyras@uef.fi.
¹⁰ Department of Applied Physics, University of Eastern Finland, Kuopio, Finland; Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland; Medical Research Center Oulu, University of Oulu, Oulu, Finland; Diagnostic Imaging Center, Kuopio University Hospital, Kuopio, Finland. Electronic address: mikko.nissi@uef.fi.

PMID: 27143363
DOI: 10.1016/j.joca.2016.04.017

Abstract

Objective: To investigate the sensitivity of quantitative magnetic resonance imaging (MRI) parameters to increase of collagen cross-linking in articular cartilage, a factor possibly contributing to the aging-related development of osteoarthritis (OA). The issue has not been widely studied although collagen cross-links may significantly affect the evaluation of cartilage imaging outcome.

Design: Osteochondral samples (n = 14) were prepared from seven bovine patellae. To induce cross-linking, seven samples were incubated in threose while the other seven served as non-treated controls. The specimens were scanned at 9.4 T for T1, T1Gd (dGEMRIC), T2, adiabatic and continuous wave (CW) T1ρ, adiabatic T2ρ and T1sat relaxation times. Specimens from adjacent tissue were identically treated and used for reference to determine biomechanical properties, collagen, proteoglycan and cross-link contents, fixed charge density (FCD), collagen fibril anisotropy and water concentration of cartilage.

Results: In the threose-treated sample group, cross-links (pentosidine, lysyl pyridinoline (LP)), FCD and equilibrium modulus were significantly (P < 0.05) higher as compared to the non-treated group. Threose treatment resulted in significantly greater T1Gd relaxation time constant (+26%, P < 0.05), although proteoglycan content was not altered. Adiabatic and CW-T1ρ were also significantly increased (+16%, +28%, P < 0.05) while pre-contrast T1 was significantly decreased (-10%, P < 0.05) in the threose group. T2, T2ρ and T1sat did not change significantly.

Conclusion: Threose treatment induced collagen cross-linking and changes in the properties of articular cartilage, which were detected by T1, T1Gd and T1ρ relaxation time constants. Cross-linking should be considered especially when interpreting the outcome of contrast-enhanced MRI in aging populations.

Keywords: Articular cartilage; Collagen; Cross-linking; Quantitative MRI; Relaxation time; Threose.

MeSH terms

Animals
Cartilage, Articular*
Cattle
Collagen
Magnetic Resonance Imaging
Osteoarthritis
Patella

Substances

Collagen