title: Quantitative in vivo CT arthrography of the human osteoarthritic knee to estimate cartilage sulphated glycosaminoglycan content: correlation with ex-vivo reference standards.
abstract: Recently, computed tomography arthrography (CTa) was introduced as quantitative imaging biomarker to estimate cartilage sulphated glycosaminoglycan (sGAG) content in human cadaveric knees. Our aim was to assess the correlation between in vivo CTa in human osteoarthritis (OA) knees and ex vivo reference standards for sGAG and collagen content.
  
  
  
  In this prospective observational study 11 knee OA patients underwent CTa before total knee replacement (TKR). Cartilage X-ray attenuation was determined in six cartilage regions. Femoral and tibial cartilage specimens harvested during TKR were re-scanned using equilibrium partitioning of an ionic contrast agent with micro-CT (EPIC-μCT), which served as reference standard for sGAG. Next, cartilage sGAG and collagen content were determined using dimethylmethylene blue (DMMB) and hydroxyproline assays. The correlation between CTa X-ray attenuation, EPIC-μCT X-ray attenuation, sGAG content and collagen content was assessed.
  
  
  
  CTa X-ray attenuation correlated well with EPIC-μCT (r = 0.76, 95% credibility interval (95%CI) 0.64 to 0.85). CTa correlated moderately with the DMMB assay (sGAG content) (r = -0.66, 95%CI -0.87 to -0.49) and to lesser extent with the hydroxyproline assay (collagen content) (r = -0.56, 95%CI -0.70 to -0.36).
  
  
  
  Outcomes of in vivo CTa in human OA knees correlate well with sGAG content. Outcomes of CTa also slightly correlate with cartilage collagen content. Since outcomes of CTa are mainly sGAG dependent and despite the fact that further validation using hyaline cartilage of other joints with different biochemical composition should be conducted, CTa may be suitable as quantitative imaging biomarker to estimate cartilage sGAG content in future clinical OA research.
authors: Department of Orthopedic Surgery, Erasmus MC, University Medical Center, Rotterdam, The Netherlands; Department of Radiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. Electronic address: j.vantiel@erasmusmc.nl.
authors: J
authors: J
authors: van Tiel
authors: Department of Orthopedic Surgery, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. Electronic address: m.siebelt@erasmusmc.nl.
authors: M
authors: M
authors: Siebelt
authors: Department of Orthopedic Surgery, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. Electronic address: m.reijman@erasmusmc.nl.
authors: M
authors: M
authors: Reijman
authors: Department of Orthopedic Surgery, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. Electronic address: p.k.bos@erasmusmc.nl.
authors: P K
authors: PK
authors: Bos
authors: Department of Orthopedic Surgery, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. Electronic address: e.waarsing@erasmusmc.nl.
authors: J H
authors: JH
authors: Waarsing
authors: TNO, Leiden, The Netherlands. Electronic address: annemariezuurmond@gmail.com.
authors: A-M
authors: AM
authors: Zuurmond
authors: Department of Biostatistics, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. Electronic address: k.nasserinejad@erasmusmc.nl.
authors: K
authors: K
authors: Nasserinejad
authors: Department of Orthopedic Surgery, Erasmus MC, University Medical Center, Rotterdam, The Netherlands; Department of Otorhinolaryngology, Erasmus MC, University Medical Center Rotterdam, The Netherlands. Electronic address: g.vanosch@erasmusmc.nl.
authors: G J V M
authors: GJ
authors: van Osch
authors: Department of Orthopedic Surgery, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. Electronic address: j.verhaar@erasmusmc.nl.
authors: J A N
authors: JA
authors: Verhaar
authors: Department of Radiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. Electronic address: g.p.krestin@erasmusmc.nl.
authors: G P
authors: GP
authors: Krestin
authors: Department of Biomechanical Engineering, Delft University of Technology, Delft, The Netherlands; Department of Orthopedics and Department of Rheumatology, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: hweinans@umcutrecht.nl.
authors: H
authors: H
authors: Weinans
authors: Department of Radiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. Electronic address: e.oei@erasmusmc.nl.
authors: E H G
authors: EH
authors: Oei
mesh_terms: D001175:Arthrography; D002358:Cartilage, Articular; D003287:Contrast Media; D006025:Glycosaminoglycans; D006801:Humans; D011446:Prospective Studies
chemical_list: D003287:Contrast Media; D006025:Glycosaminoglycans; C013786:A73025
keywords: Articular cartilage; CT arthrography; Clinical research; Knee osteoarthritis; Sulphated glycosaminoglycan content; Translational study