title: Quantitative cartilage degeneration associated with spontaneous osteoarthritis in a guinea pig model.
abstract: OBJECTIVE
  To determine (i) the feasibility and intra- and inter-scan reproducibility of T(1ρ) MRI in assessing cartilage degeneration in a guinea pig model with naturally occurring joint disease that closely mimics human osteoarthritis (OA), (ii) demonstrate the sensitivity of T(1ρ) MRI in assessing the age dependent cartilage degeneration in OA progression as compared to histopathological changes.
  
  
  METHODS
  Duncan-Hartley guinea pigs were obtained at various ages and maintained under an IACUC approved protocol. The left hind stifle joint was imaged using T(1ρ) MRI on a 9.4 Tesla Varian horizontal 20 cm bore scanner using a custom surface coil. Reproducibility of T(1ρ) MRI was assessed using 4-month-old guinea pigs (N = 3). Three age cohorts; 3 month (N = 8), 5 month (N = 6), and 9 month (N = 5), were used to determine the age-dependent osteoarthritic changes as measured by T(1ρ) MRI. Validation of age-dependent cartilage degeneration was confirmed by histology and Safranin-O staining.
  
  
  RESULTS
  T(1ρ) values obtained in the cartilage of the stifle joint in guinea pigs were highly reproducible with an inter-scan mean coefficient of variation (CV) of 6.57% and a maximum intra-scan CV of 9.29%. Mean cartilage T(1ρ) values in animals with late stage cartilage degeneration were 56.3-56.9 ms (5-9 month cohorts) were both significantly (P < 0.01) higher than that obtained from 3-month-old cohort (44 ms) demonstrating an age-dependent variation. T(1ρ) was shown to be significantly greater than T(2) . T(1ρ) dispersion was observed in this animal model for the first time showing an increase of 45% between 500 Hz and 1500 Hz spin-locking frequency. Cartilage thickness measurements were calculated from single mid-coronal histology sections from same animals used for T(1ρ) MRI. Thickness calculations showed insignificant differences between 3- and 5-month cohorts and was significantly decreased by 9 months of age (P < 0.01). A moderate correlation (R(2) = 0.45) existed between T(1ρ) values and signal intensity of Safranin-O stain.
  
  
  CONCLUSIONS
  The data presented demonstrate that T(1ρ) MRI is highly reproducible in this spontaneous model of OA and may serve as a noninvasive tool to characterize joint cartilage degeneration during OA. Age-dependent changes, verified with histological measurements of proteoglycan loss, correlated with T(1ρ) across different age groups. T(1ρ) has adequate dynamic range and is sensitive to detect and track the progression of cartilage degeneration in the guinea pig model before gross anatomical changes such as cartilage thinning has occurred. This study presents a technological advancement that would permit longitudinal studies of evaluating disease-modifying therapies useful for treating human OA.
authors: CMROI, Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. mfenty@upenn.edu
authors: Matthew C
authors: MC
authors: Fenty
authors: George R
authors: GR
authors: Dodge
authors: Victor Babu
authors: VB
authors: Kassey
authors: Walter R T
authors: WR
authors: Witschey
authors: Arijitt
authors: A
authors: Borthakur
authors: Ravinder
authors: R
authors: Reddy
mesh_terms: D000818:Animals; D002356:Cartilage / Q000473:pathology*; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D010003:Osteoarthritis / Q000473:pathology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity