ACVP 2014 IMAGING EQUINE OA REVEALS NEW INSIGHTS Sheila Laverty, MVB, Dipl. ACVS & ECVS, Professor, Department of Clinical Sciences, Director, Comparative Orthopedic Research Laboratory, Faculty of Veterinary Medicine, University of Montreal Sheila.laverty@umontreal.ca Introduction: Osteoarthritis (OA) is the most common musculoskeletal problem in equine athletes and is the most prevalent owner reported long term condition affecting horses1. The affected joints and lesion sites vary with the athletic discipline. In racehorses the metacarpophalangeal and carpal joints are most frequently involved2 whereas jumping horses are more commonly affected with tarsal (spavin) and proximal interphalangeal joint OA (ringbone). Equine OA may also arise secondary to factors such as poor joint conformation3 instability, joint incongruity (e.g. osteochondritis dissecans) and meniscal tears. Imaging equine OA pathology in a clinical setting: Imaging is crucial to accurately assess all joint structures for an OA diagnosis, prognosis and follow-up. Characteristic lesion patterns (osteophyte location and cartilage erosions) are related to repetitive loading induced trauma4. Equine practitioners diagnose OA based on clinical signs, response to intra articular anesthesia and conventional radiographic findings that include marginal osteophytes, bone sclerosis and joint space width changes (indirect measure of cartilage thickness). However, in many cases the response to intra articular anesthesia is non- specific and radiographic changes are present only in the advanced stages of disease, precluding accurate early diagnosis. Ultrasonographic examination (US) of the joint is complimentary to the radiographic examination and allows real time multi-planar imaging at a low cost and no exposure to radiation in the field. It permits visualization of synovial hypertrophy, synovial effusion5, meniscal and ligament injury, cartilage lesions, marginal osteophytes, bone erosions and fracture. Disadvantages include that it is operator dependent, cannot assess deeper structures in the joint and only the surface of bone because of the properties of sound. Nuclear scintigraphy is also a useful imaging modality for delineating areas of subchondral bone injury, inflammation and remodelling, but is non-specific and not always accessible. Magnetic resonance imaging (MRI) and computed tomography (CT) provide information on tissue structure and composition and in 3D and have greatly enhanced our understanding of OA. The evaluation of pathology is far superior to radiographs because there is no superposition. MRI permits an assessment of the complete joint (joint organ) and thereby provides new insight into the trajectory of this common disease and the associated spectrum of pathological lesions. OA pathological changes that can be imaged include cartilage fibrillation and erosion, osteophytes, bone edema, sclerosis and erosions, meniscal tears, synovial effusion and hypertrophy, capsulitis and enthesiophytosis thereby providing a more accurate early diagnosis, better management and prognosis. The capacity to image bone edema has been a major advance, although the interpretation of it’s clinical significance and what process it reflects in tissues remains a subject of debate. Many comparative imaging studies in equine OA assessing radiographs, MRI, CT and US for identification of joint lesions confirmed by arthroscopy, post mortem or histopathology have been conducted in recent years6-10. CT provides exquisite resolution of bone lesions with fast image acquisition times. CT has recently permitted the first detection of central osteophytes in equine OA that are considered more severe than marginal osteophytes9, 11. CT arthography permits evaluation of articular surface damage and ligament injury. However, as intra articular injection of contrast materiel is required, it is less likely to be widely adopted clinically. The adult equine femoropatellar and femorotibial joints pose a considerable challenge for MRI and CT technology because of their size. Very few centres worldwide have MRI or CT that can accommodate these large joints. Conventional radiographic and ultrasonographic and examinations remain mainstays in the imaging diagnosis of OA in these joints. US examination is proving particularly useful in this joint to image bone surfaces/interfaces, cartilage and soft tissue lesions. However, despite all these advances, arthroscopic visualization of the cartilage surface, though restricted to accessible sites, remains occasionally the only diagnostic tool as CT and MRI are not always accessible12. Imaging equine OA - microscopic and ultrastructural level: Just as imaging technology has revolutionized the capacity to diagnose OA in the clinics, it is also changing how OA lesions may be visualized at the microscopic and ultrastructural levels ex vivo. It has been known for some time that racehorses develop severe osteochondral lesions in the dorsal carpal bones and the palmar metacarpus following repeated loads of racing and training. The lesions in the equine palmar metacarpal condyle, a form of post- traumatic osteoarthritis, were initially defined as “traumatic osteochondrosis”13 but more recently the term palmar osteochondral disease (POD)14 has been employed to describe them. A study employing scanning electron microscopy (SEM) of these lesions in racehorse joints with OA revealed that microcracks arise in sclerotic bone probably due to microdamage accumulation from repetitive loads15. Subchondral bone failure and focal collapse of cartilage into the lesion arises and was posited to be due to an osteoclastic remodelling response that further weakens the bone, but the exact cause of progression remains to be elucidated. A subsequent study employing back scattered EM and SEM on similar specimens revealed that highly mineralized projections were observed extending from cracks in the calcified cartilage into the hyaline cartilage and were associated with surface fibrillation16. It is now possible with uCT to non-destructively image cartilage and bone samples without preparation and generate 3 D images of morphology, internal microstructure. Recently we reported uCT examination of 3rd carpal bones from racehorses with different stages of OA. Striking deep focal resorptive changes were observed in the subchondral bone with subchondral pits that were related to cartilage OA changes and potentially fracture17. Additional studies in the same specimens employing traditional histology and immunohistochemistry has revealed the presence of large numbers of osteoclasts and a positive correlation between osteoclast density and porosity, microcrack number in calcified cartilage and histological cartilage degeneration score18, confirming activated remodeling and osteoclast recruitment at these sites adding new insight into this disease. In a recent study of tarsal OA in young horses CT proved very useful for detection of focal OA changes ex vivo8. In the same joints a combination of confocal scanning microscopy, backscatter SEM (employing iodine) and uCT revealed elegant images of early OA pathology9. The authors also reported that joint margin lesions were not associated with lesions observed deeper in the joints and similar mineralized projections were observed in these joints to those observed previously in the fetlock joint16 highlighting a potential role of this novel lesion in equine OA pathology in general. There was also a close association between hyaline articular cartilage and calcified cartilage lesions, as we observed in our carpal studies. Additional new imaging techniques for the study equine cartilage include second harmonic generation microscopy19 that reveals collagen network structure, high frequency ultrasound to assess cartilage structure and the cartilage bone interface20, 21 and optical coherence tomography21. Although these techniques remain in the realm of research settings we can look forward to some of these technologies percolating towards the clinics in coming years. Imaging equine OA in the future: In the clinical arena we will see more powerful MRI’s10 in the future. In addition advanced MRI imaging such as compositional MRI that allows visualization of the biochemical composition and structure of joint tissues will be employed to detect early OA changes. The earliest molecular changes in OA are biochemical involving the two most abundant molecules of the cartilage matrix, type II collagen and proteoglycan. Gadolinium enhanced magnetic imaging of cartilage (dGEMRIC)22 and T1rho relaxation time mapping permit assessment of the proteoglycan component of the matrix whereas T2 mapping provides information on the collagen network23. These specialized sequences hold the promise to detect the earliest matrix changes prior to irreversible structural events. Similarly smart arthroscopes will be equipped with sensors that will allow intrarticular ultrasonography using high frequency ultrasound to assess the cartilage structure, image the cartilage bone junction and more accurately image partial thickness lesions20, 21. Summary: Conventional radiography, despite it’s shortcomings, remains a mainstay technique for diagnosing OA in both equine and human medicine in clinics. US examination is a valuable complementary diagnostic tool as it is able to provide real time information on the 3D aspect of osteophytes and is more sensitive than radiographs. Standing MRI is now also widely used and is providing novel information on the equine lower limb joints. The equine stifle and hock joints remain a challenge for sophisticated imaging techniques. 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