title: Region of interest analysis: by selecting regions with denuded areas can we detect greater amounts of change?
abstract: BACKGROUND
  Based on recent analyses, the measures of short-term responsiveness of magnetic resonance imaging (MRI) derived cartilage morphometry may not be as large as earlier studies had suggested. We examined if by selecting regions of interest with denuded cartilage, the remaining cartilage within this region of interest was susceptible to greater rates of cartilage loss.
  
  
  METHODS
  Subjects included for this analysis are a subset of the approximately 4700 participants in the Osteoarthritis Initiative (OAI) Study. Bilateral radiographs and 3T MRI (Siemens Trio) of the knees and clinical data are obtained at baseline and annually in all participants. Hundred and fifty subjects from the OAI progression subcohort all of whom had both frequent symptoms and, in the same knee, radiographic osteoarthritis (ROA defined as definite tibio-femoral osteophytes on X-ray) based on a screening reading done at the OAI clinics. One knee from each subject was selected for analysis. Using sagittal 3D DESSwe MR images from the baseline and 12-month follow-up visit, a segmentation algorithm was applied to the cartilage plates of the index knee to compute the cartilage volume, normalized cartilage volume (volume normalized to bone surface interface area), and percent denuded area (Total Cartilage Bone Interface area denuded of cartilage). Summary statistics of the changes (absolute and percentage) from baseline at 1 year and the standardized response mean (SRM), i.e., mean change divided by the standard deviation (SD) of that change were calculated. Analyses are stratified into three groups according to baseline assessment of denuded area: those with no denuded area in the region of interest at baseline, and then two groups (intermediate denuded area (<or=median) and severe (>or=median) denuded area) of equal sample size.
  
  
  RESULTS
  On average the subjects were 60.9 years of age and obese with a mean body mass index (BMI) of 30.3 kg/m(2). For the combined central medial femur and tibia the mean volume change for the whole sample was -48.2 (SD 159.8) mm(3), which gives an SRM of -0.30. In the subsample of knees with no denuded area the SRM was -0.25, in the knees with intermediate denuded area the SRM was -0.30, and in knees with severe denuded area the SRM was -1.00. For normalized volume of the central medial femur in the subsample of knees with no denuded area the SRM was -0.22, in the knees with intermediate denuded area the SRM was -0.26, and in knees with severe denuded area (n=23) the SRM was -0.71. The magnitude of the SRMs was generally smaller in participants with no denuded area. In contrast, the SRMs in participants with denuded area were larger.
  
  
  CONCLUSIONS
  By selecting participants with the presence of cartilage regions with denuded area the ability to demonstrate change in cartilage loss in that specific location is markedly improved compared to persons without a full thickness lesion in that cartilage plate. This option for screening during recruitment in clinical trials could facilitate the detection of participants at greater risk of subsequent cartilage loss.
authors.affiliation: Division of Research, New England Baptist Hospital, Boston, MA 02120, USA. djhunter@caregroup.harvard.edu
authors.forename: D J
authors.initials: DJ
authors.lastname: Hunter
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.forename: Y Q
authors.initials: YQ
authors.lastname: Zhang
authors.forename: S
authors.initials: S
authors.lastname: Totterman
authors.forename: J
authors.initials: J
authors.lastname: Tamez
authors.forename: C K
authors.initials: CK
authors.lastname: Kwoh
authors.forename: C B
authors.initials: CB
authors.lastname: Eaton
authors.forename: M-P Hellio
authors.initials: MP
authors.lastname: Le Graverand
authors.forename: C R
authors.initials: CR
authors.lastname: Beals
mesh_terms: D000368:Aged; D000465:Algorithms; D015992:Body Mass Index; D002358:Cartilage, Articular / Q000473:pathology*; D005260:Female; D005269:Femur / Q000473:pathology; D005500:Follow-Up Studies; D006801:Humans; D007719:Knee Joint / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000473:pathology*; D013977:Tibia / Q000473:pathology