Clinical magnetic resonance-enabled characterization of mono-iodoacetate-induced osteoarthritis in a large animal species

• Published in: PloS one Vol. 13; no. 8; p. e0201673
• Main Authors: Unger, Mark D, Murthy, Naveen S, Kanwar, Rahul, Strand, Kasey A, Maus, Timothy P, Beutler, Andreas S
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03-08-2018; Public Library of Science (PLoS)
• Subjects: Anesthesiology; Animal models; Animal species introduction; Animals; Arthritis; Biocompatibility; Biology and Life Sciences; Body Size; Bone marrow; Care and treatment; Cartilage; Cartilage diseases; Characterization; Degeneration; Departments; Development and progression; Disease Models, Animal; Disease Progression; Drug dosages; Edema; Evaluation; Global health; Homology; Hospital costs; Humans; Injection; Injections, Intra-Articular - methods; Iodoacetic Acid - adverse effects; Knee; Knee Joint - diagnostic imaging; Laboratory animals; Livestock; Magnetic resonance; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Medical imaging; Medical research; Medicine and Health Sciences; Multivariate analysis; NMR; Nuclear magnetic resonance; Oncology; Osteoarthritis; Osteoarthritis, Knee - chemically induced; Osteoarthritis, Knee - diagnostic imaging; Pain; Pain management; Public health; Research and Analysis Methods; Resonance; Structural damage; Surgery; Surgical instruments; Swine; Ultrasonography; Ultrasound; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0201673

Osteoarthritis (OA) is the most common form of arthritis. Medical and surgical treatments have yet to substantially diminish the global health and economic burden of OA. Due to recent advances in clinical imaging, including magnetic resonance imaging (MRI), a correlation has been established between structural joint damage and OA-related pain and disability. Existing preclinical animal models of OA are useful tools but each suffers specific roadblocks when translating structural MRI data to humans. Intraarticular injection of mono-iodoacetate (MIA) is a reliable, well-studied method to induce OA in small animals but joint size discrepancy precludes the use of clinical grade MRI to study structural disease. The porcine knee is suited for clinical MRI and demonstrates homology with humans. We set out to establish the first large animal model of MIA-induced knee OA in swine characterized by structural MRI.
Yucatan swine (n = 27) underwent ultrasound-guided injection of knees with 1.2, 4, 12, or 40 mg MIA. MRI was performed at several time points over 12 weeks (n = 54 knees) and images were assessed according to a modified clinical grading scheme. Knees were harvested and graded up to 35 weeks after injection.
MIA-injected knees (n = 25) but not control knees (n = 29) developed gross degeneration. A total of n = 6,000 MRI measurements were recorded by two radiologists. MRI revealed progressive cartilage damage, bone marrow edema, erosions, and effusions in MIA-injected knees. Lesion severity and progression was influenced by time, dose, and inter-individual variability.
Intraarticular injection of MIA produced structural knee degradation that was reliably characterized using clinical MRI in swine. Destruction was progressive and, similar to human OA, lesion severity was heterogeneous between and within treatment groups.