New imaging tools for mouse models of osteoarthritis

Abstract

Osteoarthritis (OA) is a chronic degenerative disease characterized by a disruption of articular joint cartilage homeostasis. Mice are the most commonly used models to study OA. Despite recent reviews, there is still a lack of knowledge about the new development in imaging techniques. Two types of modalities are complementary: those that assess structural changes in joint tissues and those that assess metabolism and disease activity. Micro MRI is the most important imaging tool for OA research. Automated methodologies for assessing periarticular bone morphology with micro-CT have been developed allowing quantitative assessment of tibial surface that may be representative of the whole OA joint changes. Phase-contrast X-ray imaging provides in a single examination a high image precision with good differentiation between all anatomical elements of the knee joint (soft tissue and bone). Positron emission tomography, photoacoustic imaging, and fluorescence reflectance imaging provide molecular and functional data. To conclude, innovative imaging technologies could be an alternative to conventional histology with greater resolution and more efficiency in both morphological analysis and metabolism follow-up. There is a logic of permanent adjustment between innovations, 3R rule, and scientific perspectives. New imaging associated with artificial intelligence may add to human clinical practice allowing not only diagnosis but also prediction of disease progression to personalized medicine.

Keywords: Imaging; Innovation; Mouse models; Osteoarthritis; Technologies.

Fig. 1

Representative images of one MIA knee mouse model of OA observed by 3D imaging techniques Image reprinted with permission from [43]. A MRI with a ultrashort echo time sequence (echo time = 0.00813 ms; repetition time = 4.0 ms; flip angle = 5 degree; voxel size = 50 × 50 × 50 µm³. B Conventional X-ray micro-tomography image (source voltage = 60 kVp; voxel size = 6 × 6 × 6 µm³). C Synchrotron X-ray phase-contrast imaging (source energy = 52 keV; voxel size = 6.1 × 6.1 × 6.1µm³)

Fig. 2

Positron emission tomography of rat knees. Image reprinted with permission from [67]. Legend: coronal 18F-fluoride PET images (2 W). a ACLT knee (2 W), b sham (2 W). ACLT knee (a) shows a higher uptake of 18F-fluoride especially in the medial femur and medial tibia than sham-operated knee (b), consistent with results by gamma counting of resected specimen

Fig. 3

Ultrasound Imaging of a mouse knee. Image reprinted with permission from [70]. A An ultrasound B-mode image of a mouse knee joint. B Outlined joint space (solid green), tibia, and femur on the ultrasound B-mode image. C Alcian blue/orange G (ABOG)-stained knee section with outlined joint space detected by ultrasound. D Illustration shows 3D reconstruction of join space derived from a stack of ultrasound B-mode images

Fig. 4

In vivo fluorescence reflectance imaging of protease activity in a mouse model of posttraumatic osteoarthritis. Image reprinted with permission from [76]. Representative pseudo-colored images of male and female mice imaged with MMPSense fluorescent tracers