In vivo visualization using MRI T₂ mapping of induced osteochondrosis and osteochondritis dissecans lesions in goats undergoing controlled exercise

Abstract

In vivo visualization of subclinical osteochondrosis(OC) lesions, characterized by necrosis of epiphyseal growth cartilage, is necessary to clarify the pathogenesis of this disease. Hence, our objectives were to demonstrate induced necrosis of the epiphyseal cartilage in vivo using MRI and to monitor progression or resolution of resulting lesions. We also aimed to improve the goat model of OC by introducing controlled exercise. Vascular supply to the epiphyseal cartilage was surgically interrupted in four 5-day-old goats to induce ischemic cartilage necrosis in a medial femoral condyle. Starting 3 weeks postoperatively, goats underwent daily controlled exercise until euthanasia at 6, 10, 11 (n=2) weeks postoperatively. T2 maps of operated and control femora were obtained in vivo at 3(n=4), 6(n=4), 9(n=3) and 11(n=2) weeks postoperatively using a 3T MR scanner. In vivo MRI findings were validated against MRI results obtained ex vivo at 9.4T in three goats and compared to histological results in all goats. Surgical interruption of the vascular supply caused ischemic cartilage necrosis in 3 out of 4 goats. T2 maps obtained in vivo at 3T identified regions of increased relaxation time consistent with discrete areas of cartilage necrosis 3 to 11 weeks postoperatively and demonstrated delayed progression of the ossification front at 9(n=1) and 11(n=2) weeks postoperatively. In vivo MRI findings were confirmed by ex vivo MRI at 9.4T and by histology. Identification of cartilage necrosis in clinical patients in the early stages of OC using T2 maps may provide valuable insight into the pathogenesis of this condition.

Evaluation of the Suitability of Miniature Pigs as an Animal Model of Juvenile Osteochondritis Dissecans

“…Failure of endochondral ossification was defined as the presence of focally thickened cartilage accompanied by a focal delay in the progression of the ossification front at the chondro‐osseous junction. Cartilage necrosis was defined as the combined presence of shrunken, necrotic chondrocytes (characterized by pyknotic nuclei) and altered staining (pallor), sometimes accompanied by cystic degeneration (an area where loss of tissue/matrix components results in clear spaces replacing the matrix), of the surrounding matrix …”

“…Goats were selected for these earlier studies based on their previous successful use as animal models of orthopedic disease, small size to enable imaging in available MRI scanners, and relatively long lifespan, while initially no consideration was given to vascular anatomy. We found that epiphyseal cartilage lesions triggered by interruption of the vascular supply in the goats were limited in size and exhibited a low propensity to develop into clinically apparent OCD . Results of subsequent studies identified a vascular architecture characterized by the presence of short, branching vessels with abundant collateral circulation in the caprine distal femoral epiphyseal cartilage that was markedly different from that seen in human subjects and domestic swine .…”

“…Cartilage necrosis was defined as the combined presence of shrunken, necrotic chondrocytes (characterized by pyknotic nuclei) and altered staining (pallor), sometimes accompanied by cystic degeneration (an area where loss of tissue/matrix components results in clear spaces replacing the matrix), of the surrounding matrix. 13,14…”

“…12 These requirements are illustrated by results of previous studies that attempted to use goats to model JOCD and were only successful in inducing subclinical disease. 13,14 In these studies, most of the induced OC latens and OC manifesta lesions exhibited signs of repair rather than developing into clinically apparent disease. Rich, collateral vascular supply to the distal femoral epiphyseal cartilage present in goats, but absent in humans, likely mediated this enhanced healing process.…”

“…Furthermore, disease induction in the prospective animal model should involve manipulation of the epiphyseal vascular supply . These requirements are illustrated by results of previous studies that attempted to use goats to model JOCD and were only successful in inducing subclinical disease . In these studies, most of the induced OC latens and OC manifesta lesions exhibited signs of repair rather than developing into clinically apparent disease.…”