title: Rapid, automated imaging of mouse articular cartilage by microCT for early detection of osteoarthritis and finite element modelling of joint mechanics.
abstract: OBJECTIVE
  Mouse articular cartilage (AC) is mostly assessed by histopathology and its mechanics is poorly characterised. In this study: (1) we developed non-destructive imaging for quantitative assessment of AC morphology and (2) evaluated the mechanical implications of AC structural changes.
  
  
  METHODS
  Knee joints obtained from naïve mice and from mice with osteoarthritis (OA) induced by destabilization of medial meniscus (DMM) for 4 and 12 weeks, were imaged by phosphotungstic acid (PTA) contrast enhanced micro-computed tomography (PTA-CT) and scored by conventional histopathology. Our software (Matlab) automatically segmented tibial AC, drew two regions centred on each tibial condyle and evaluated the volumes included. A finite element (FE) model of the whole mouse joint was implemented to evaluate AC mechanics.
  
  
  RESULTS
  Our method achieved rapid, automated analysis of mouse AC (structural parameters in <10 h from knee dissection) and was able to localise AC loss in the central region of the medial tibial condyle. AC thickness decreased by 15% at 4 weeks and 25% at 12 weeks post DMM surgery, whereas histopathology scores were significantly increased only at 12 weeks. FE simulations estimated that AC thinning at early-stages in the DMM model (4 weeks) increases contact pressures (+39%) and Tresca stresses (+43%) in AC.
  
  
  CONCLUSIONS
  PTA-CT imaging is a fast and simple method to assess OA in murine models. Once applied more extensively to confirm its robustness, our approach will be useful for rapidly phenotyping genetically modified mice used for OA research and to improve the current understanding of mouse cartilage mechanics.
authors.affiliation: Department of Bioengineering, Imperial College London, London SW7 2AZ, UK.
authors.forename: P
authors.initials: P
authors.lastname: Das Neves Borges
authors.affiliation: Department of Mechanical Engineering, Imperial College London, London SW7 2AZ, UK.
authors.forename: A E
authors.initials: AE
authors.lastname: Forte
authors.affiliation: Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7HE, UK.
authors.forename: T L
authors.initials: TL
authors.lastname: Vincent
authors.affiliation: Department of Mechanical Engineering, Imperial College London, London SW7 2AZ, UK.
authors.forename: D
authors.initials: D
authors.lastname: Dini
authors.affiliation: Department of Bioengineering, Imperial College London, London SW7 2AZ, UK; Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7HE, UK. Electronic address: m.marenzana@imperial.ac.uk.
authors.forename: M
authors.initials: M
authors.lastname: Marenzana
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002358:Cartilage, Articular / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology; D003287:Contrast Media; D004195:Disease Models, Animal; D042241:Early Diagnosis; D021621:Imaging, Three-Dimensional; D007719:Knee Joint / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology; D008592:Menisci, Tibial / Q000601:surgery; D051379:Mice; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology; D010772:Phosphotungstic Acid; D013977:Tibia / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology; D055114:X-Ray Microtomography
chemical_list: D003287:Contrast Media; D010772:Phosphotungstic Acid
keywords: 3-dimensional quantitative imaging; Destabilisation of medial meniscus model; High-throughput automated image analysis; Micro computed tomography; Mouse articular cartilage