title: Separation of healthy and early osteoarthritis by automatic quantification of cartilage homogeneity.
abstract: OBJECTIVE
  Cartilage loss as determined either by magnetic resonance imaging (MRI) or by joint space narrowing in X-rays is the result of cartilage erosion. However, metabolic processes within the cartilage that later result in cartilage loss may be a more accurate assessment method for early changes. Early biological processes of cartilage destruction are among other things, a combination of proteoglycan turnover, as a result of altered charge distributions, and local alterations in water content (edema). As water distribution is detectable by MRI, the aim of this study was to investigate cartilage homogeneity visualized by MRI related to water distribution, as a potential very early marker for early detection of knee osteoarthritis (OA).
  
  
  METHODS
  One hundred and fourteen right and left knees from 71 subjects aged 22-79 years were scanned using a Turbo 3D T(1) sequence on a 0.18T MRI Esaote scanner. The medial compartment of the tibial cartilage sheet was segmented using a fully automatic voxel classification scheme based on supervised learning. From the segmented cartilage sheet, homogeneity was quantified by measuring entropy from the distribution of signal intensities inside the compartment. For each knee an X-ray was acquired and the knees were categorized by the Kellgren and Lawrence (KL) index and the joint space width (JSW) was measured. The P-values for separating the groups by each of JSW, cartilage volume, cartilage mean intensity, and cartilage homogeneity were calculated using the unpaired t-test.
  
  
  RESULTS
  The P-value for separating the group diagnosed as KL 0 from the group being KL 1 based on JSW, volume and mean signal intensity the values were P=0.9, P=0.4 and P=0.0009, respectively. In contrast, the P-value for homogeneity was P=0.0004. The precision of the measures assessed, as a test-retest root mean square coefficient of variation (RMS-CV%) was 3.9% for JSW, 7.4% for volume, 3.9% for mean signal intensity and 3.0% for homogeneity quantification.
  
  
  CONCLUSIONS
  These data demonstrate that the distribution of components of the articular matrix precedes erosion, as measured by cartilage homogeneity related to water concentration. We show that homogeneity was able to separate early OA from healthy individuals in contrast to traditional volume and JSW quantifications. These data suggest that cartilage homogeneity quantification may be able to quantify early biochemical changes in articular cartilage prior to cartilage loss and thereby provide better identification of patients for OA trials who may respond better to medicinal intervention of some treatments. In addition, this study supports the feasibility of using low-field MRI in clinical studies.
authors.affiliation: Image Group, University of Copenhagen, Denmark.
authors.forename: A A
authors.initials: AA
authors.lastname: Qazi
authors.forename: J
authors.initials: J
authors.lastname: Folkesson
authors.forename: P C
authors.initials: PC
authors.lastname: Pettersen
authors.forename: M A
authors.initials: MA
authors.lastname: Karsdal
authors.forename: C
authors.initials: C
authors.lastname: Christiansen
authors.forename: E B
authors.initials: EB
authors.lastname: Dam
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D002358:Cartilage, Articular / Q000000981:diagnostic imaging / Q000473:pathology*; D018450:Disease Progression; D042241:Early Diagnosis; D006801:Humans; D007719:Knee Joint / Q000000981:diagnostic imaging / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008875:Middle Aged; D015999:Multivariate Analysis; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging / Q000473:pathology*; D011859:Radiography; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers