Session Type: Abstract Submissions (ACR)
One of the fundamental shortcomings in the field of experimental rheumatology is the inability to non-invasively monitor the development of inflammatory arthritis longitudinally. Magnetic resonance imaging (MRI) overcomes this limitation, by allowing for detailed examination of anatomical structures as well as the assessment of joint and soft tissue inflammation. Here, we have utilized cutting-edge MRI technologies to image ankle joints in control (C57BL/6) and arthritic (K/BxN serum transfer-induced arthritis (STIA) and K/BxAg7) mice over time. Further, the MRI data was validated against both clinical, histological, and in vivo imaging system (IVIS) assessments of inflammatory arthritis.
C57BL/6 mice were injected with PBS (controls) or 100 mL of K/BxN serum at day 0. Mice were scored clinically and imaged via IVIS and MRI at days 0, 3, 7, 15, and 21 after arthritis induction. MRI imaging was also performed on ankle joints from 10- and 21-week-old K/BxAg7 mice. Arthritis severity was assessed by measurement of ankle width and clinical score. Decalcified ankle joint specimens were sectioned and stained with hematoxylin and eosin for histological analysis. Luminescence acquisition was performed using an IVIS Spectrum System 10 minutes after intraperitoneal injection of 100 mL (200 mg/kg) of XenoLight Rediject Inflammation Probe. Radiance signal intensity from normalized gated analyses of forepaw and hindpaw joints was quantified utilizing Living Image software. Ankle joint MRI was performed on a 9.4T Bruker Biospec MRI system. Two high-resolution 3D images were acquired; a gradient echo pulse sequence (FLASH) to evaluate bone and a spin echo sequence (MSME) to evaluate inflammation (long T2 signal volume). Amira software was used to perform MRI long T2 signal analyses and bone reconstructions. Graphpad Prism software was used for ANOVA and linear regression analyses with statistical significance established at p < 0.05.
Arthritic STIA animals demonstrated increased clinical, histological, IVIS, and MRI measures of disease severity compared to controls. Peak arthritis intensity occurred at day 7 and complete resolution of inflammation was observed by day 21. Following induction of arthritis, the majority of increased long T2 signal and volume expansion of ankle joints occurred in a juxtaarticular rather than intrarticular fashion. Ankle joint bone destruction in K/BxAg7 mice was readily detectible via MRI as early as age 10 weeks. Linear regression analyses demonstrated a strong correlation between clinical score and paw joint radiance intensity by IVIS (R2 = 0.54, p <0.0001). There was also a statistically significant relationship between ankle joint width and volume of long T2 signal by MRI (R2 = 0.57, p <0.0001).
MRI is an optimal technology for anatomic localization of articular and soft tissue changes during the development and resolution of inflammatory arthritis. Future studies may combine MRI imaging with various in vivo labeling agents to investigate joint disease in a cell-type specific fashion.
S. M. Rose,
H. R. Perlman,
E. A. Waters,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/imaging-of-ankle-joints-by-mri-in-murine-models-of-inflammatory-arthritis/