OBJECTIVE: To evaluate the impact of two MRI sequences on cartilage defect assessment in knee OA patients and the sensitivity to change over time comparing cartilage defect (semi-quantitative) with cartilage volume loss (quantitative) methods. METHODS: GRE and IW-FSE sequences were compared. Knee OA MRI were from two 2-year studies (cohort 1, n=55; cohort 2, n=143). For both cohorts, a GRE sequence was used and patients of cohort 1 underwent an additional IW-FSE. Cohort 2 included patients from a previous trial. Cartilage defects and cartilage volume were evaluated. RESULTS: The cartilage defect assessment provided consistent significantly higher scores in IW-FSE than in GRE sequences at baseline and 2 years. However, there was no difference in the change at 2 years between the sequences. SRM for change did not show difference between the two sequences but was consistently higher (2-2.5 fold) for the quantitative method. Cartilage defect score change between two treatment groups revealed a trend toward significance only in the medial tibial plateau, whereas the change in cartilage volume loss demonstrated significant difference in global knee, femur, lateral femur, and lateral compartment. SRM for the treatment groups combined were markedly higher for cartilage volume loss than for defect by 4.3 to 6.0. CONCLUSION: The direct comparison between GRE and IW-FSE sequences did not suggest superior sensitivity to cartilage defect change over time of one sequence over the other. Interestingly, the quantitative cartilage volume assessment was more sensitive than the semi-quantitative scoring in the detection of treatment effect on OA cartilage changes. © 2012 by the American College of Rheumatology.