title: Effect of collagen cross-linking on quantitative MRI parameters of articular cartilage.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 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.
authors.forename: J
authors.initials: J
authors.lastname: Rautiainen
authors.affiliation: 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.
authors.forename: M T
authors.initials: MT
authors.lastname: Nieminen
authors.affiliation: Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland. Electronic address: elli-noora.salo@iki.fi.
authors.forename: E-N
authors.initials: EN
authors.lastname: Salo
authors.affiliation: Diagnostic Imaging Center, Kuopio University Hospital, Kuopio, Finland. Electronic address: harri.t.kokkonen@gmail.com.
authors.forename: H T
authors.initials: HT
authors.lastname: Kokkonen
authors.affiliation: Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, USA. Electronic address: mangia@umn.edu.
authors.forename: S
authors.initials: S
authors.lastname: Mangia
authors.affiliation: Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, USA. Electronic address: shalom@cmrr.umn.edu.
authors.forename: S
authors.initials: S
authors.lastname: Michaeli
authors.affiliation: Department of Neurobiology, A.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland. Electronic address: olli.grohn@uef.fi.
authors.forename: O
authors.initials: O
authors.lastname: Gröhn
authors.affiliation: Department of Applied Physics, University of Eastern Finland, Kuopio, Finland; Diagnostic Imaging Center, Kuopio University Hospital, Kuopio, Finland. Electronic address: jukka.jurvelin@uef.fi.
authors.forename: J S
authors.initials: JS
authors.lastname: Jurvelin
authors.affiliation: Department of Applied Physics, University of Eastern Finland, Kuopio, Finland; Diagnostic Imaging Center, Kuopio University Hospital, Kuopio, Finland. Electronic address: juha.toyras@uef.fi.
authors.forename: J
authors.initials: J
authors.lastname: Töyräs
authors.affiliation: 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.
authors.forename: M J
authors.initials: MJ
authors.lastname: Nissi
mesh_terms: D000818:Animals; D002358:Cartilage, Articular; D002417:Cattle; D003094:Collagen; D008279:Magnetic Resonance Imaging; D010003:Osteoarthritis; D010329:Patella
chemical_list: D003094:Collagen
keywords: Articular cartilage; Collagen; Cross-linking; Quantitative MRI; Relaxation time; Threose