Spatial gradients in articular cartilage structure trend toward homogeneity with onset and progression of osteoarthritis (OA). Exploiting MRI, we compared heterogeneous variations in tissue structure, and the corresponding function, to OA severity through the use of spatial first derivatives, herein termed functional gradient indices (FGIs), providing new biomarkers indicating tissue state. We evaluated FGI maps of MRI data visualizing osteochondral human explants and OAI subjects for relationships to OA severity. FGI data correlated significantly with tissue health, while traditional metrics did not. The sensitivity and versatility of FGI analysis suggests a novel biomarker with improved detection of early disease pathogenesis.