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Early diagnosis of cartilage disease at a time when changes are limited to depletion of extracellular matrix components represents an important diagnostic target to reduce patient morbidity. This report is to present proof of concept for nanoparticle dependent cartilage barrier imaging in a large animal model including the use of clinical magnetic resonance imaging (MRI). Conditioned (following matrix depletion) and unconditioned porcine metacarpophalangeal cartilage was evaluated on the basis of fluorophore conjugated 30 nm and 80 nm spherical gold nanoparticle permeation and multiphoton laser scanning and bright field microscopy after autometallographic particle enhancement. Consequently, conditioned and unconditioned joints underwent MRI pre- and post-injection with 12 nm superparamagnetic iron oxide nanoparticles (SPIONs) to evaluate particle permeation in the context of matrix depletion and use of a clinical 1.5 Tesla MRI scanner. To gauge the potential pro-inflammatory effect of intra-articular nanoparticle delivery co-cultures of equine synovium and cartilage tissue were exposed to an escalating dose of SPIONs and IL-6, IL-10, IFN-γ and PGE2 were assessed in culture media. The chemotactic potential of growth media samples was subsequently assessed in transwell migration assays on isolated equine neutrophils. Results demonstrate an increase in MRI signal following conditioning of porcine joints which suggests that nanoparticle dependent compositional cartilage imaging is feasible. Tissue culture and neutrophil migration assays highlight a dose dependent inflammatory response following SPION exposure which at the imaging dose investigated was not different from controls. The preliminary safety and imaging data support the continued investigation of nanoparticle dependent compositional cartilage imaging. To our knowledge, this is the first report in using SPIONs as intra-articular MRI contrast agent for studying cartilage barrier function, which could potentially lead to a new diagnostic technique for early detection of cartilage disease.

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BackgroundCheek teeth (second through fourth premolars and first through third molars) diastema is a common and painful equine disorder caused by the absence of effective tight interdental contact between these teeth. Limited objective information is available on the angulation of equine cheek teeth that control dental drift or on mesial or distal equine cheek teeth drift that should normally prevent this disorder.ObjectivesTo measure the angulation of the mesial and distal cheek teeth in horses of different ages, quantify age-related cheek teeth mesial and distal dental drift, and measure the cheek teeth row length in horses of different ages.Study DesignRetrospective review of computed tomographic images of equine heads.MethodsCase details and CT images from clinical equine cases that had undergone standing CT head examination were collated.Three sets of measurements were acquired from each head. “Head size” calculated as the distance between the caudal aspect of the orbit and the caudal aspect of the naso-incisive notch was used to standardize measurements in different sized heads. The length of the cheek teeth rows measured from the mesial aspect of the Triadan 06 occlusal surface to the distal aspect of the Triadan 11 occlusal surface. The rostro-caudal (antero-posterior) position and angulation of the mandibular and maxillary Triadan 06 and 11 teeth were measured in relation to reference lines drawn on CT images.ResultsSignificant mesial drift occurred in the maxillary and mandibular Triadan 11s. Despite their distal angulation, the upper and lower Triadan 06s also drifted mesially. The mean angulation of Triadan 06 and 11 mandibular teeth (17.8 and 26.2°, respectively) was almost double that of maxillary teeth (9.2 and 13.3°, respectively) with both Triadan 11s having greater angulation than the 06s. Cheek teeth angulation only significantly decreased in the mandibular 06s. Cheek teeth arcade lengths decreased with age, but these decreases were not significant.Main LimitationsLimitations include the relatively small sample size.ConclusionsIn the population of horses used for this study, age related mesial drift occurred in both Triadan 06 and 11s, and the angulation of these teeth did not decrease with age in most arcades.