Ultrasound Can Detect Macroscopically Undetectable Changes in Osteoarthritis Reflecting the Superficial Histological and Biochemical Degeneration: Ex Vivo Study of Rabbit and Human Cartilage

Abstract

Recognizing subtle cartilage changes in the preclinical stage of osteoarthritis (OA) is essential for early diagnosis. To this end, the ability of the ultrasound signal intensity to detect macroscopically undetectable cartilage change was investigated. In this study, cartilage of rabbit OA model and human OA samples was examined by macroscopic evaluation, ultrasound signal intensity, histology with Mankin scores, and Fourier transform infrared imaging (FTIRI) analysis. Rabbit OA was induced by anterior cruciate ligament transection and evaluated at 1, 2, 4 and 12 weeks. Twenty human samples were harvested during total knee arthroplasty from OA patients who had macroscopically normal human cartilage (ICRS grade 0) on the lateral femoral condyle. In the animal study, there was no macroscopic OA change at 2 weeks, but histology detected degenerative changes at this time point. Ultrasound signal intensity also detected degeneration at 2 weeks. In human samples, all samples were obtained from macroscopically intact site, however nearly normal (0≤ Mankin score <2), early OA (2≤ Mankin score <6), and moderate OA (6≤ Mankin score <10) samples were actually intermixed. Ultrasound signal intensity was significantly different among these 3 stages and was well correlated with Mankin scores (R = −0.80) and FTIR parameters related to collagen and proteoglycan content in superficial zone. In conclusion, ultrasound can detect microscopic cartilage deterioration when such changes do not exist macroscopically, reflecting superficial histological and biochemical changes.

Animal models of osteoarthritis: classification, update, and measurement of outcomes

“…Aside from synovitis, these techniques can detect intraosseous cysts; lesions in the meniscus, bone, and ACL; and subchondral bone defects and can also map articular synovial space. Ultrasound has found some success in animals and humans to detect other early osteoarthritic changes [ 33 , 267 ]. The ultrasound serves as a quicker and cost effective method to study outcomes in animals (Table 5 ).…”

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“…The histological scoring of the sections was performed by three unwitting researchers using the Mankin scoring system. According to the classification of Mankin and his colleagues, the score is divided into four stages: near normal (0–2), early (2–6), middle (6–10), and late (10–14) ( Iannitti et al, 2013 ; Nishitani et al, 2014 ).…”

How precisely does ultrasonographic evaluation reflect the histological status of the articular cartilage of the knee joint?

“…We have previously shown in an in vitro study using a specific US system to detect early changes in the articular cartilage that US grades correlate well with histological grades. 7 However, we did not evaluate in vivo changes or analyze degenerative changes or the thickness of the articular cartilages.…”