title: Osteoarthritic cartilage is more homogeneous than healthy cartilage: identification of a superior region of interest colocalized with a major risk factor for osteoarthritis.
abstract: OBJECTIVE
  Cartilage loss as determined by magnetic resonance imaging (MRI) or joint space narrowing as determined by x-ray is the result of cartilage erosion. However, metabolic processes within the cartilage that later result in cartilage loss may be a more sensitive assessment method for early changes. Recently, it was shown that cartilage homogeneity visualized by MRI representing the biochemical changes undergoing in the cartilage is a potential marker for early detection of knee osteoarthritis (OA) and is also able to significantly separate groups of healthy subjects from those with OA. The purpose of this study was twofold. First, we wished to evaluate whether the results on cartilage homogeneity from the previous study can be reproduced using an independent population. Second, based on the homogeneity framework, we present an automatic technique that partitions the region of interest in the cartilage that contributes most to discrimination between healthy and OA subjects and allows for identification of the most implicated areas in early OA. These findings may allow further investigation of whether cartilage homogeneity reveals a predisposition for OA or whether it evolves as a consequence to disease and thereby can be used as a progression biomarker.
  
  
  METHODS
  A total of 283 right and left knees from 159 subjects aged 21 to 81 years were scanned using a Turbo 3D T1 sequence on a 0.18-T 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. Each knee was examined by radiography, and the knees were categorized by the Kellgren and Lawrence (KL) Index. Next, based on a gradient descent optimization technique, the cartilage region that contributed to the maximum statistical significance of homogeneity in separating healthy subjects from the diseased was partitioned. The generalizability of the region was evaluated by testing for overfitting. Three different regularization techniques were evaluated for reducing overfitting errors.
  
  
  RESULTS
  The P values for separating the different groups based on cartilage homogeneity were 2 x 10(-5) (KL 0 versus KL 1) and 1 x 10(-7) (KL 0 versus KL >0). Using the automatic gradient descent technique, the partitioned region was toward the peripheral part of the cartilage sheet. Using this region, the P values for separating the different groups based on homogeneity were 5 x 10(-9) (KL 0 versus KL 1) and 1 x 10(-15) (KL 0 versus KL >0). The precision of homogeneity for the partitioned region assessed as a test-retest root-mean-square coefficient of variation was 3.3%. Bootstrapping proved to be an effective regularization tool in reducing overfitting errors.
  
  
  CONCLUSIONS
  The validation study supported the use of cartilage homogeneity as a tool for the early detection of knee OA and for separating groups of healthy subjects from those who have disease. Our automatic, unbiased partitioning algorithm based on a general statistical framework outlined the cartilage region of interest that best separated healthy from OA conditions on the basis of homogeneity discrimination. We have shown that OA affects certain areas of the cartilage more distinctly, and these areas are located more toward the peripheral region of the cartilage. We propose that this region corresponds anatomically to cartilage covered by the meniscus in healthy subjects. This finding may provide valuable clues in the early detection and monitoring of OA and thus may improve treatment efficacy.
authors: Image Group, University of Copenhagen, Copenhagen, Denmark. arish@diku.dk
authors: Arish A
authors: AA
authors: Qazi
authors: Erik B
authors: EB
authors: Dam
authors: Mads
authors: M
authors: Nielsen
authors: Morten A
authors: MA
authors: Karsdal
authors: Paola C
authors: PC
authors: Pettersen
authors: Claus
authors: C
authors: Christiansen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000175:diagnosis*; D012307:Risk Factors