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The purpose of this study is to evaluate the ability of a machine learning algorithm to classify in vivo magnetic resonance images (MRI) of human articular cartilage for development of osteoarthritis (OA). Sixty‐eight subjects were selected from the osteoarthritis initiative (OAI) control and incidence cohorts. Progression to clinical OA was defined by the development of symptoms as quantified by the Western Ontario and McMaster Universities Arthritis (WOMAC) questionnaire 3 years after baseline evaluation. Multi‐slice T₂‐weighted knee images, obtained through the OAI, of these subjects were registered using a nonlinear image registration algorithm. T₂ maps of cartilage from the central weight bearing slices of the medial femoral condyle were derived from the registered images using the multiple available echo times and were classified for “progression to symptomatic OA” using the machine learning tool …