Early findings of small-animal MRI and small-animal computed tomography correlate with histological changes in a rat model of rheumatoid arthritis

Abstract

With the use of a commonly utilized animal model of rheumatoid arthritis, the central goal of this work was to determine how well the small-animal imaging tools, small-animal MRI (microMRI) and small-animal X-ray computed tomography (microCT), can detect very early histological changes that occur immediately after induction of the disease. Arthritis was induced in rats by injecting complete Freund's adjuvant into the tail. Right hind paws of living rats were evaluated with 4.7 T microMRI with T1-weighted spin echo and inversion recovery sequences. Paw specimens were also evaluated with microCT and by histological examination (n = 29). MicroMR images were scored for the presence of joint effusion, soft tissue swelling, bone marrow changes, and bone erosions. MicroCT measured bone mineral density (BMD). Histology scores were obtained from representative slides from the same rats. The correlation between BMD, MRI and histology was analyzed using linear regression analysis and analysis of covariance. MRI abnormalities were detected on day 5 after induction as joint effusion and soft tissue swelling, followed by bone marrow changes on day 6 and bone erosion on day 8. BMD measured by microCT decreased, the decrease becoming significant on day 7 (P < 0.019). Soft tissue swelling, joint effusion, and bone erosion scores on microMRI correlated with histology (r2 approximately 0.7). Bone marrow changes were seen more clearly with microMRI than by histological examination. Bone loss could be detected earlier by microCT than on histological sections. In conclusion, microMRI and microCT can be used to evaluate early disease changes within 1 week of induction in the adjuvant-induced arthritis model, and have the ability to detect certain manifestations of disease earlier than histological analysis. The use of small-animal imaging techniques potentially allows earlier diagnosis, improved subject stratification, earlier drug implementation, and therefore improved drug trials in animal models of rheumatoid arthritis.