1University of Pennsylvania, Philadelphia, PA, United States, 2Nemours Biomedical Research A.I. duPont Hospital for Children, Wilmington, DE, United States,.
T1ρ MRI of Experimentally Induced Osteoarthritis in a Porcine Animal Model A. J. Wheaton1, A. Borthakur1, G. R. Dodge2, J. DiCesare2, H. R. Schumacher3, R. Reddy1 1
University of Pennsylvania, Philadelphia, PA, United States, 2Nemours Biomedical Research A.I. duPont Hospital for Children, Wilmington, DE, United States, 3 Department of Medicine University of Pennsylvania, Philadelphia, PA, United States
Synopsis T1ρ-weighted MR images were used to quantitatively measure experimentally induced osteoarthritis in an in vivo porcine model. Six pigs were given an injection of porcine IL-1β 6 h prior to undergoing T1ρ MRI. The T1ρ relaxation rate (1/T1ρ) of IL-1β treated patellae was measured to be 29% lower than control patellae indicating a loss of proteoglycan. The MR data is in accordance with histochemical and immunochemical findings.
Introduction Articular cartilage is comprised mainly of an extracellular matrix (ECM) of collagen, proteoglycan (PG), and chondrocytes. The early stages of the degenerative disease osteoarthritis (OA) are primarily associated with a loss of PG and minimal changes in collagen. T1ρ MRI has previously been proposed as a noninvasive method to quantitatively detect changes in the PG content of cartilage (1). T1ρ, the spin-lattice relaxation in the rotating frame, is sensitive to the slow motion interactions between water and surrounding macromolecules such as PG. Interleukin-1β (IL-1β) is a cytokine associated with the production of matrix metalloproteinases (MMPs) by chondrocytes. Cartilage PG molecules act as substrates for MMP-3 and MMP-13, both of which are stimulated by IL-1β (2). In the present study, we used a pig model where a bolus of IL-1β was directly injected in the joint space. The contralateral knee served as the saline injected control. We chose to analyze the cartilage after 6 h since preliminary studies revealed that an injection of IL-1β produced changes that plateaued after approximately 6 h. Presumably this result is related to factors such as the necessary diffusion time and cytokine stability. The dose of IL-1 was theorized to affect the chondrocytes by stimulating an increase in the production of MMPs thereby resulting in conditions that closely mimic the early stages of osteoarthritis.
Methods
Six 3 to 5 month old pigs were administered an injection of 100 ng of porcine IL-1β (R&D Systems) in 1 mL of saline in the joint space of the right knee and a control injection of 1 mL of saline in the contralateral knee 6 h prior to imaging. The pigs were imaged on a 4T GE Signa system using a single-slice 2D FSE sequence with a linear transmit/receive surface coil and employing imaging parameters of FOV = 10cm x 10cm, slice thickness = 3mm, acquisition matrix = 256 x 128, echo train length = 4, effective TE = 17 ms, and TR = 4 s for a total imaging time of 2 minutes. The FSE sequence was pre-encoded with a T1ρ spin lock sequence and the spin lock time was varied from 10 ms to 50 ms using five even steps. Immediately after imaging, the patellae were harvested and imaged using a quadrature birdcage coil with identical imaging settings. The images were fitted using a least squares regression to create a T1ρ map. T1ρ was measured as the average value of the map in a region of interest containing the entire patella. After imaging, the ex vivo patellae were processed for routine histology and stained for PG content using Alcian blue-PAS. Synovial fluid was sampled and analyzed for signs of inflammation and presence of MMPs.
Results The in vivo and ex vivo T1ρ measurements were highly correlated yielding a slope of 1.07 (R2 = 0.957, p
