title: Localized 3D analysis of cartilage composition and morphology in small animal models of joint degeneration.
abstract: OBJECTIVE
  Current histological scoring methods to evaluate efficacy of potential therapeutics for slowing or preventing joint degeneration are time-consuming and semi-quantitative in nature. Hence, there is a need to develop and standardize quantitative outcome measures to define sensitive metrics for studying potential therapeutics. The objectives of this study were to use equilibrium partitioning of an ionic contrast agent via Equilibrium Partitioning of an Ionic Contrast-Microcomputed tomography (EPIC-μCT) to quantitatively characterize morphological and compositional changes in the tibial articular cartilage in two distinct models of joint degeneration and define localized regions of interest to detect degenerative cartilage changes.
  
  
  METHODS
  The monosodium iodoacetate (MIA) and medial meniscal transection (MMT) rat models were used in this study. Three weeks post-surgery, tibiae were analyzed using EPIC-μCT and histology. EPIC-μCT allowed measurement of 3D morphological changes in cartilage thickness, volume and composition.
  
  
  RESULTS
  Extensive cartilage degeneration was observed throughout the joint in the MIA model after 3 weeks. In contrast, the MMT model showed more localized degeneration with regional thickening of the medial tibial plateau and a decrease in attenuation consistent with proteoglycan (PG) depletion. Focal lesions were also observed and 3D volume calculated as an additional outcome metric.
  
  
  CONCLUSIONS
  EPIC-μCT was used to quantitatively assess joint degeneration in two distinct preclinical models. The MMT model showed similar features to human Osteoarthritis (OA), including localized lesion formation and PG loss, while the MIA model displayed extensive cartilage degeneration throughout the joint. EPIC-μCT imaging provides a rapid and quantitative screening tool for preclinical evaluation of OA therapeutics.
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, USA. tthote@gatech.edu
authors.forename: T
authors.initials: T
authors.lastname: Thote
authors.forename: A S P
authors.initials: AS
authors.lastname: Lin
authors.forename: Y
authors.initials: Y
authors.lastname: Raji
authors.forename: S
authors.initials: S
authors.lastname: Moran
authors.forename: H Y
authors.initials: HY
authors.lastname: Stevens
authors.forename: M
authors.initials: M
authors.lastname: Hart
authors.forename: R V
authors.initials: RV
authors.lastname: Kamath
authors.forename: R E
authors.initials: RE
authors.lastname: Guldberg
authors.forename: N J
authors.initials: NJ
authors.lastname: Willett
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D002358:Cartilage, Articular / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D007091:Image Processing, Computer-Assisted / Q000379:methods; D019807:Iodoacetic Acid; D008297:Male; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013977:Tibia / Q000473:pathology; D000070600:Tibial Meniscus Injuries; D055114:X-Ray Microtomography / Q000379:methods
chemical_list: D011509:Proteoglycans; D019807:Iodoacetic Acid
keywords: EPIC-μCT; Joint degeneration; MIA; MMT; Rat