IN VIVO MICRO COMPUTED TOMOGRAPHY IMAGING ALLOWS LONGITUDINAL ASSESSMENT OF MULTI-SCALE CHANGES TO WHOLE JOINT WITH PROGRESSION OF OA

Abstract

INTRODUCTION

Longitudinal assessment of knee joint structure holds promise for providing invaluable spatial-temporal information on the progression of degenerative musculoskeletal (MSK) diseases involving the knee joint.

OBJECTIVE

This proof-of-concept study aims to establish a time-lapse in vivo imaging protocol with high temporal resolution to longitudinally track multi-scale structural changes, including mechanical alteration to whole joint structure, sensitive microstructural changes to subchondral bone, and abnormal bone remodeling activity, in a mouse collagenase-induced osteoarthritis (OA) model.

METHODS

Eight male C57BL/10 mice aged nine weeks were recruited and assigned to two longitudinal groups, control (CT) and OA. Of these, four ten-week-old mice assigned to the OA group received intra-articular injection of collagenase on the right knee to destabilize the right tibiofemoral joint. Longitudinal in vivo micro-computed tomography (microCT) scans were performed one day before collagenase injection and then weekly for eight weeks in total, resulting in nine scans for each animal. In vivo microCT (Scanco Medical) was performed with a source voltage of 70 kVp, an integration time of 350 ms, a current of 114 μA, and an isotropic nominal resolution of 10.4 μm with 1000 projections, with each scanning taking around 30 minutes. Quantitative morphometric analysis (QMA) was performed to measure longitudinal changes to structure of whole joint and subchondral bone, including joint space width (mm), and trabecular thickness (mm). Visualization of dynamic bone remodeling was performed by registering serial microCT scans. Bone resorption rate, BRR (%/day), and bone formation rate, BFR (%/day) were measured to quantify bone remodeling activity. To test the differences between CT and OA group at each time point from week 1 to week 8, a one-way analysis of covariance was used.

RESULTS

Three weeks post OA-induction, a significantly smaller joint space width was observed in medial osteoarthritic joint (202 μm), when compared to CT joint (228 μm) (p < 0.01). Regarding trabecular thickness, significant differences were observed at multiple time points between CT and OA groups, specifically in the first three weeks at the early stage of OA progression at lateral side (p < 0.01). Representative 3D visualization of bone formation and bone resorption is shown in Figure 1 A-B. Abnormal bone remodeling activities were observed in osteoarthritic femur. When compared to control femur, significantly larger bone resorption rate was observed in the first week post collagenase injection in both the lateral (p < 0.01) and medial femur (p < 0.01), as shown in Figure 1 C-D.

CONCLUSION

This proof-of-concept study, for the first time, demonstrated the application of longitudinal in vivo microCT imaging protocol for tracking whole joint mechanical malalignment, monitoring subchondral bone microstructure changes, visualizing and quantifying abnormal bone remodeling activity in a collagenase-induced OA mice model. Combined with future gait analysis and mechanical loading tests, we hope to use this approach to provide deeper insights into the mechanism and pathogenesis of MSK disorders, thus facilitating early diagnosis, intervention, and treatment development and assessment.