In vivo quantification of collagen-induced arthritis mouse model by three-dimensional volumetric ultrasound and color Doppler.

Abstract

Purpose: Ultrasound combined with Doppler techniques has been widely utilized to evaluate joint inflammation and internal structural changes in animal models of rheumatoid arthritis. However, previous assessments using these techniques were predominantly semi-quantitative, which may limit the precision and reliability of the results. Therefore, the primary objective of this study was to explore the potential advantages of three-dimensional (3D) volumetric ultrasound and color Doppler in quantitatively assessing the progression of disease.

Objective: To quantify the severity and progression of collagen-induced arthritis (CIA) mouse model using a micro-imaging tool, 3D volumetric ultrasound and color Doppler, and assess if 3D model-based volumetric changes of joint space and vascularity correlate with clinical, histological and bone destruction findings.

Methods: CIA was induced in mice on a DBA/1J background at 7 ~ 8 weeks of age. 3D volumetric ultrasound and color Doppler analysis was performed on knee and ankle joints of all mice using the Vevo 2100 system at 0, 2, 4, 8 weeks after the booster immunization. Clinical, histological and bone destruction analysis were performed as usual. Correlation analysis of the volumetric changes of joint space and vascularity with clinical, histological and bone destruction score were assessed via Spearman's test.

Results: It was possible to quantify the severity of joint inflammation and intra-articular changes during the progression of CIA by 3D volumetric ultrasound and color Doppler. The 3D model-based volumetric changes of joint space and vascularity have significant correlations with clinical, histological and bone destruction score of arthritis.

Conclusions: We demonstrated that 3D volumetric ultrasound and color Doppler is a noninvasive, quantitative tool for evaluating CIA mice in vivo. Despite certain limitations, those technology significantly enhance our ability to monitor disease progression and severity, assess therapeutic interventions, and reduce reliance on invasive techniques.