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Preclinical imaging in osteoarthritis is a rapidly growing area with three principal objectives: to provide rapid, sensitive tools to monitor the course of experimental OA longitudinally; to describe the temporal relationship between tissue-specific pathologies over the course of disease; and to use molecular probes to measure disease activity in vivo. Research in this area can be broadly divided into those techniques that monitor structural changes in tissues (microCT, microMRI, ultrasound) and those that detect molecular disease activity (positron emission tomography (PET), optical and optoacoustic imaging). The former techniques have largely evolved from experience in human joint imaging and have been refined for small animal use. Some of the latter tools, such as optical imaging, have been developed in preclinical models and may have translational benefit in the future for patient stratification and for monitoring disease progression and response to treatment. In this narrative review we describe these methodologies and discuss the benefits to animal research, understanding OA pathogenesis, and in the development of human biomarkers., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To detect and determine disease severity of osteoarthritis (OA) using a probe activated by matrix metalloproteinase-13 (MMP-13) in vivo in the murine destabilised medial meniscus (DMM) surgical model of OA., Design: We have previously described MMP12ap and MMP13ap, internally quenched fluorescent peptide substrate probes that are activated respectively by MMP-12 and MMP-13. Here we used these probes to follow enzyme activity in vivo in mice knees 4, 6 and 8 weeks following DMM surgery. After in vivo optical imaging, disease severity was determined through traditional histological analysis. The amount of probe activation was analysed for discrimination between DMM, contralateral and sham operated knees, as well as for congruence between activity and histological damage., Results: There was no specific activation of MMP12ap at the time points observed between sham operated and DMM operated, or their respective contralateral joints. The activation of the MMP13ap in the DMM model was highest 6 weeks after surgery, but was only specific compared against sham surgery 8 weeks after surgery (1.5-fold increase). The activation of MMP13ap correlated with histological damage 6 and 8 weeks after surgery, with correlations of 0.484 (P = 0.0032) and 0.478 respectively (P = 0.0049). This correlation dropped to 0.218 (P = 0.011) if all data were considered., Conclusion: The current MMP-13 activity probe is suitable for the discrimination between DMM and sham or contralateral knees 8 weeks after surgery, when cartilage loss is typified by the appearance of small fissures up to the tidemark, but not earlier. This activity correlates with the histological damage observed., (Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)