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This paper studied the changing pattern of knee cartilage using 3D knee magnetic resonance (MR) images over a 12-month period. As a pilot study, we focused on the medial tibia compartment of the knee joint. To quantify the thickness of cartilage in this compartment, we utilized two methods: one was measurement through manual segmentation of cartilage on each slice of the 3D MR sequence; the other was measurement through cartilage damage index (CDI), which quantified the thickness on a few informative locations on cartilage. We employed the artificial neural networks (ANNs) to model the changing pattern of cartilage thickness. The input feature space was composed of the thickness information at a cartilage location as well as its neighborhood from baseline year data. The output categories were ‘changed’ and ‘no-change’, based on the thickness difference at the same location between the baseline year and the 12-month follow-up data. Different ANN models were trained by using CDI features and manual segmentation features. Further, for each type of feature, individual models were trained at different subregions of the medial tibia compartment, i.e., the bottom part, the middle part, the upper part, and the whole. Based on the experiment results, we found that CDI features generated better prediction performance than manual segmentation, on both whole medial tibia compartment and any subregion. For CDI, the best performance in term of AUC was obtained using the central CDI locations (AUC = 0.766), while the best performance for manual segmentation was obtained using all slices of the 3D MR sequence (AUC = 0.656). As experiment results showed, the CDI method demonstrated a stronger pattern of cartilage change than the manual segmentation method, which required up to 6-hour manual delineation of all MRI slices. The result should be further validated by extending the experiment to other compartments.