Magnetic Resonance Imaging of Osteophytic, Chondral, and Subchondral Structures in a Surgically-Induced Osteoarthritis Rabbit Model

Abstract

ObjectiveThis study aimed to assess changes in osteophytic, chondral, and subchondral structures in a surgically-induced osteoarthritis (OA) rabbit model in order to correlate MRI findings with the macroscopic progress of OA and to define the timepoint for disease status in this OA model.MethodsThe OA model was constructed by surgery in thirty rabbits with ten normal rabbits serving as controls (baseline). High-resolution three-dimensional MRI using a 1.5-T coil was performed at baseline, two, four, and eight weeks post-surgery. MRIs of cartilage lesions, subchondral bone lesions, and osteophyte formations were independently assessed by two blinded radiologists. Ten rabbits were sacrificed at baseline, two, four, and eight weeks post-surgery, and macroscopic evaluation was independently performed by two blinded orthopedic surgeons.ResultsThe signal intensities and morphologies of chondral and subchondral structures by MRI accurately reflected the degree of OA. Cartilage defects progressed from a grade of 0.05–0.15 to 1.15–1.30 to 1.90–1.97 to 3.00–3.35 at each successive time point, respectively (p<0.05). Subchondral bone lesions progressed from a grade of 0.00 to 0.78–0.90 to 1.27–1.58 to 1.95–2.23 at each successive time point, respectively (p = 0.000). Osteophytes progressed from a size (mm) of 0.00 to 0.87–1.06 to 1.24–1.87 to 2.21–3.21 at each successive time point, respectively (p = 0.000).ConclusionsSerial observations revealed that MRI can accurately detect the progression of cartilage lesions and subchondral bone edema over an eight-week period but may not be accurate in detecting osteophyte sizes. Week four post-surgery was considered the timepoint between OA-negative and OA-positive status in this OA model. The combination of this OA model with MRI evaluation should provide a promising tool for the pre-clinical evaluation of new disease-modifying osteoarthritis drugs.

Protective effect of zoledronic acid on articular cartilage and subchondral bone of rabbits with experimental knee osteoarthritis

“…MRI is able to accurately detect the progression of cartilage lesions and subchondral bone edema over an eight-week period ( 13 ). In the present study, this quantitative MRI technique was used to measure the thickness of cartilage.…”

“…Assessment of radiological joint space narrowing by X-ray radiography is the ‘gold standard’ for assessing OA, while there is currently no well-established imaging modality to visualize and quantify changes in chondral and subchondral tissue ( 13 ). MRI, with superior soft tissue contrast, is the best technique available for the assessment of normal articular cartilage and cartilage lesions ( 23 ).…”

“…The assessment of structural changes by MRI had been previously investigated in a canine model of ACLT-induced OA ( 24 ) and in a guinea pig model of spontaneous OA ( 25 ). However, the changes in chondral and subchondral structures in a rabbit model of ACLT-induced OA have remained to be thoroughly investigated ( 13 ). The present study used 3D-FS-SPGR and T2 mapping techniques.…”

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

“…MRI has also been used to acquire 3D images of cartilage volume loss in a naturally occurring OA caused by obesity in the guinea pig model [ 245 ]. Some surgical models which induce OA and have used MRI to study changes include ACLT and Medial Meniscus Tear [ 244 , 246 ]. In much smaller animal models such as mice, standard MRI measurements are not possible; however, micro-MRI has been utilized to study ACLT induced OA [ 247 ] and in Brtl mouse models [ 248 ].…”

An MRI Evaluation of Patients Who Underwent Treatment with a Cell-Mediated Gene Therapy for Degenerative Knee Arthritis: A Phase IIa Clinical Trial

“…For example, Jia et al performed an MRI analysis of OA in rabbit models, and they noted that at as little as 8 weeks, cartilage defects, subchondral bone lesions, and osteophyte size significantly progressed (p < 0.05). 23 In addition, Crema et al through the Multicenter Osteoarthritis Study observed that worsening of cartilage damage was more frequently observed than meniscal damage, with an associated increased risk in joint space narrowing. 24 Furthermore, additional assessments showed a decrease in the size of a large cartilage blister, the near complete filling of a small full-thickness cartilage defect, an increase in cartilage thickness in a large defect and remodeling of the underlying bone.…”