title: Contrast-Enhanced Nanofocus X-Ray Computed Tomography Allows Virtual Three-Dimensional Histopathology and Morphometric Analysis of Osteoarthritis in Small Animal Models.
abstract: 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.
  
  
  METHODS
  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. CE-nanoCT 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.
authors.affiliation: Biomechanics Research Unit, Université de Liège, Liège, Belgium ; Prometheus, Division of Skeletal Tissue Engineering Leuven, KU Leuven, Leuven, Belgium ; Department of Metallurgy and Materials Engineering, KU Leuven, Heverlee, Belgium.
authors.forename: Greet
authors.initials: G
authors.lastname: Kerckhofs
authors.affiliation: TiGenix NV, Leuven, Belgium.
authors.forename: Julie
authors.initials: J
authors.lastname: Sainz
authors.affiliation: Prometheus, Division of Skeletal Tissue Engineering Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Marina
authors.initials: M
authors.lastname: Maréchal
authors.affiliation: Department of Metallurgy and Materials Engineering, KU Leuven, Heverlee, Belgium.
authors.forename: Martine
authors.initials: M
authors.lastname: Wevers
authors.affiliation: TiGenix NV, Leuven, Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Van de Putte
authors.affiliation: Biomechanics Research Unit, Université de Liège, Liège, Belgium ; Prometheus, Division of Skeletal Tissue Engineering Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Liesbet
authors.initials: L
authors.lastname: Geris
authors.affiliation: Prometheus, Division of Skeletal Tissue Engineering Leuven, KU Leuven, Leuven, Belgium ; Department of Metallurgy and Materials Engineering, KU Leuven, Heverlee, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Schrooten
keywords: 3D cartilage quantification; contrast-enhanced nanofocus computed tomography (CE-nanoCT); modified Mankin scoring; osteoarthritis; virtual histopathology