Approaches to optimize analyses of multidimensional ordinal MRI data in osteoarthritis research: A perspective.

Objective: Knee osteoarthritis (OA) is a disease of the whole joint involving multiple tissue types. MRI-based semi-quantitative (SQ) scoring of knee OA is a method to perform multi-tissue joint assessment and has been shown to be a valid and reliable way to measure structural multi-tissue involvement and progression of the disease. While recent work has described how SQ scoring may be used for clinical trial enrichment and disease phenotyping in OA, less guidance is available for how these parameters may be used to assess study outcomes. Design: Here we present recommendations for summarizing disease progression within specific tissue types. We illustrate how various methods may be used to quantify longitudinal change using SQ scoring and review examples from the literature. Results: Approaches to quantify longitudinal change across subregions include the count of number of subregions, delta-subregion, delta-sum, and maximum grade changes. Careful attention should be paid to features that may fluctuate, such as bone marrow lesions, or with certain interventions, for example pharmacologic interventions with anticipated cartilage anabolic effects. The statistical approach must align with the nature of the outcome. Conclusions: SQ scoring presents a way to understand disease progression across the whole joint. As OA is increasingly recognized as a heterogeneous disease with different phenotypes a better understanding of longitudinal progression across tissue types may present an opportunity to match study outcome to patient phenotype or to treatment mechanism of action.