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.

Preclinical positron emission tomography scanner based on a monolithic annulus of scintillator: initial design study

“…Application of this paradigm has been reduced over the last two decades with the introduction of high-resolution scanners designed for imaging of small animals. [1][2][3][4][5][6][7][8] It is now possible to perform longitudinal studies on relatively small cohorts of animals. The application of radiopharmaceutical-based molecular imaging techniques is of particular interest to investigators due to the ability to track and quantify physiologic processes.…”

Histopathology in Mouse Models of Rheumatoid Arthritis

“…By contrast, reporting of scores for individual features of interest can reduce interobserver discrepancies and provide detail on type and pathogenesis of lesions. The latter can be further augmented by combination with quantitative data based on histomorphometry [79] or provided by imaging modalities such as micro-CT or MRI [80][81][82]. If overall lesion severity scores are required in efficacy studies to evaluate group differences of treatment effects, such scores can easily be derived by combining individual feature scores into overall lesion scores.…”

Upconversion nanoprobes for efficiently in vitro imaging reactive oxygen species and in vivo diagnosing rheumatoid arthritis

“…Although promising, most of the contrast agents used in these modalities lack specificity and only provide information on anatomic changes (e.g. bone demineralization and joint space narrowing) that are later manifestations of RA [4,5]. These drawbacks make it difficult to identify specific molecular or cellular changes involved in RA and restrict their effectiveness as a method for short-term assessment of treatment response [7,8].…”