The inability to detect early degenerative changes to the articular cartilage surface that commonly precede bulk osteoarthritic degradation is an obstacle to early disease detection for research or clinical diagnosis. Leveraging a known artefact that blurs tissue boundaries in clinical arthrograms, contrast agent (CA) diffusivity can be derived from computed tomography arthrography (CTa) scans. We combined experimental and computational approaches to study protocol variations that may alter the CTa-derived apparent diffusivity. In experimental studies on bovine cartilage explants, we examined how CA dilution and transport direction (absorption versus desorption) influence the apparent diffusivity of untreated and enzymatically digested cartilage. Using multiphysics simulations, we examined mechanisms underlying experimental observations and the effects of image resolution, scan interval and early scan termination. The apparent diffusivity during absorption decreased with increasing CA concentration by an amount similar to the increase induced by tissue digestion. Models indicated that osmotically-induced fluid efflux strongly contributed to the concentration effect. Simulated changes to spatial resolution, scan spacing and total scan time all influenced the apparent diffusivity, indicating the importance of consistent protocols. With careful control of imaging protocols and interpretations guided by transport models, CTa-derived diffusivity offers promise as a biomarker for early degenerative changes.