Functional Imaging in Osteoarthritis: Bridging Mechanistic Insight and Therapeutic Translation

Functional imaging provides a decision-oriented framework for evaluating osteoarthritis (OA) beyond late structural morphology. OA is a heterogeneous, aging-associated whole-joint disease in which cartilage matrix disruption, synovial inflammation, subchondral bone remodelling, altered mechanics, and pain-circuitry changes may evolve before radiographic end-stage features dominate. Conventional radiography and symptom scores remain indispensable, but they provide limited information about active biological processes and are often poorly aligned with pain, progression risk, or treatment response. In this Perspective, we argue that functional imaging should be selected according to a defined decision context rather than technical novelty alone. Quantitative and compositional magnetic resonance imaging (MRI), dynamic contrast-enhanced MRI, selected positron emission tomography (PET)-based approaches, procedure-linked optical coherence tomography, neurofunctional imaging, mass spectrometry imaging, and isotope-informed spatial methods occupy different positions along the translational pathway. Near-term clinical and trial value is most plausible for risk enrichment, mechanistic phenotyping, longitudinal monitoring, and target-engagement assessment; discovery platforms remain essential for target nomination and endotype refinement. We therefore propose a restrained roadmap that separates candidate signals from qualified biomarkers and prioritises reproducibility, biological specificity, and clinical utility.