Abstract
The mouse model of osteoarthritis (OA) has been recognized as the most promising research tool for the identification of new OA therapeutic targets. However, this model is currently limited by poor throughput, dependent on the extremely time-consuming histopathology assessment of the articular cartilage (AC). We have recently shown that AC in the rat tibia can be imaged both in air and in saline solution using a laboratory system based on coded-aperture X-ray phase-contrast imaging (CAXPCi). Here, we explore ways to extend the methodology for imaging the much thinner AC of the mouse, by means of gold-standard synchrotron-based phase-contrast methods. Specifically, we have used analyser-based phase-contrast micro-computed tomography (micro-CT) for its high sensitivity to faint phase changes, coupled with a high-resolution (4.5 μm pixel) detector. Healthy, diseased (four weeks post induction of OA) and artificially damaged mouse AC was imaged at the Elettra synchrotron in Trieste, Italy, using the above method. For validation, we used conventional micro-CT combined with radiopaque soft-tissue staining and standard histomorphometry. We show that mouse cartilage can be visualized correctly by means of the synchrotron method. This suggests that: (i) further developments of the laboratory-based CAXPCi system, especially in terms of pushing the resolution limits, might have the potential to resolve mouse AC ex vivo and (ii) additional improvements may lead to a new generation of CAXPCi micro-CT scanners which could be used for in vivo longitudinal pre-clinical imaging of soft tissue at resolutions impossible to achieve by current MRI technology.
Highlights
Osteoarthritis (OA) is a pathology of the articular joint affecting up to one-third of the population older than 50 years and, owing to the current lack of effective treatments, its prevalence and social burden is predicted to increase with the ageing population worldwide [1]
250 mm (b) from the three-dimensional reconstruction) of the mouse tibial epiphysis obtained by synXPC micro-CT enables the visualization of the cartilage interface in a similar way to the image of the coronal section of rat tibial epiphysis obtained by coded-aperture X-ray phasecontrast imaging (CAXPCi)
Our findings demonstrate that mouse articular cartilage (AC) can be visualized by high-resolution synXPC microCT, and that the image quality resembles that of rat cartilage imaged with the laboratory-based CAXPCi system, especially in terms of the mechanism that makes the cartilage layer visible
Summary
Osteoarthritis (OA) is a pathology of the articular joint affecting up to one-third of the population older than 50 years and, owing to the current lack of effective treatments, its prevalence and social burden is predicted to increase with the ageing population worldwide [1]. This lack of progress in the development of effective cures for OA is largely due to the difficulty in diagnosing early cartilage lesions. The potential of the mouse model of OA is currently limited by its poor throughput, largely dependent on the extremely time-consuming histopathology assessment of the articular cartilage (AC). Conventional histology does not allow the sample structure to be reconstructed and visualized in three dimensions, and neither simultaneous, multiple views (e.g. coronal and sagittal and cross-sectional) of the sample nor three-dimension-based quantitative measurements such as tissue volume, thickness and surface are possible
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