In osteoarthritis, articular cartilage loses integrity and becomes thinned. This usually occurs at sites which bear weight during normal use. Measurement of such loss from MRI scans, requires precise and reproducible techniques, which can overcome the difficulties of patient repositioning within the scanner. In this study, we combine a previously described technique for segmentation of cartilage from MRI of the knee, with a technique for 3D image registration that matches localized regions of interest at followup and baseline. Two patients, who had recently undergone meniscal surgery, and developed lesions during the 12 month followup period were examined. Image registration matched regions of interest (ROI) between baseline and followup, and changes within the cartilage lesions were estimate to be about a 16% reduction in cartilage volume within each ROI. This was more than 5 times the reproducibility of the measurement, but only represented a change of between 1 and 2% in total femoral cartilage volume. Changes in total cartilage volume may be insensitive for quantifying changes in cartilage morphology. A combined used of automated image segmentation, with 3D image registration could be a useful tool for the precise and sensitive measurement of localized changes in cartilage from MRI of the knee.