Utilization of longitudinal ultrasound to quantify joint soft-tissue changes in a mouse model of posttraumatic osteoarthritis

Hao Xu,Ronald W Wood,Edward M Schwarz,Yongjun Wang,Echoe M Bouta,Lianping Xing

doi:10.1038/boneres.2017.12

Abstract

To assess the utility of longitudinal ultrasound (US) to quantify volumetric changes in joint soft tissues during the progression of posttraumatic osteoarthritis (PTOA) in mice, and validate the US results with histological findings. A longitudinal cohort of 3-month-old wild-type C57BL/6 male mice received the Hulth-Telhag surgical procedure on right knee to induce PTOA, and sham surgery on their left knee as control. US scans were performed on both knees before, 2, 4, 6, and 8 weeks post-surgery. Joint space volume and Power-Doppler (PD) volume were obtained from US images via Amira software. A parallel cross-sectional cohort of mice was killed at each US time point, and knee joints were subjected to histological analysis to obtain synovial soft-tissue area and OARSI scores. The correlation between US joint space volume and histological synovial soft-tissue area or OARSI score was assessed via linear regression analysis. US images indicated increased joint space volume in PTOA joints over time, which was associated with synovial inflammation and cartilage damage by histology. These changes started from 2 weeks post-surgery and gradually became more severe. No change was detected in sham joints. Increased joint space volume was significantly correlated with increased synovial soft-tissue area and the OARSI score (P<0.001). PD signal was detected in the joint space of PTOA joints at 6 weeks post-surgery, which was consistent with the location of blood vessels that stained positively for CD31 and alpha-smooth muscle actin in the synovium. This study indicates that US is a cost-effective longitudinal outcome measure of volumetric and vascular changes in joint soft tissues during PTOA progression in mice, which positively correlates with synovial inflammation and cartilage damage.

Highlights

Osteoarthritis (OA) is a progressing joint disorder manifested by pain and disability of affected joints, which can be initiated and exacerbated by trauma
Our group applied US scan on joints of TNF transgenic mice,5 a mouse model of rheumatoid arthritis (RA). We demonstrated that both joint space volume and Power Doppler (PD) volume can be used as outcome measures of joint inflammation and active synovitis
To validate whether the change of joint space volume that is detected by US reflects a pathologic change in synovial soft tissues and cartilage, we performed Hulth-Telhag and sham surgery in a parallel cross-sectional experiment, and killed mice at the same time points as we have done for US

Summary

Introduction

Osteoarthritis (OA) is a progressing joint disorder manifested by pain and disability of affected joints, which can be initiated and exacerbated by trauma. Plain radiography and magnetic resonance imaging are commonly clinical used imaging modalities to assess the severity of knee OA.. Plain radiography and magnetic resonance imaging are commonly clinical used imaging modalities to assess the severity of knee OA.1–3 These imaging methods are rarely used in preclinical animal models of OA, especially in mice. Radiography does not always show joint space narrowing in mouse OA, which may be because of insufficient resolution of X-ray and anatomical structure. The use of magnetic resonance imaging is limited due to high costs and need for special magnetic resonance imaging.

Methods

Results

Conclusion