Imaging technologies for preclinical models of bone and joint disorders

Abstract

Preclinical models for musculoskeletal disorders are critical for understanding the pathogenesis of bone and joint disorders in humans and the development of effective therapies. The assessment of these models primarily relies on morphological analysis which remains time consuming and costly, requiring large numbers of animals to be tested through different stages of the disease. The implementation of preclinical imaging represents a keystone in the refinement of animal models allowing longitudinal studies and enabling a powerful, non-invasive and clinically translatable way for monitoring disease progression in real time. Our aim is to highlight examples that demonstrate the advantages and limitations of different imaging modalities including magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), single-photon emission computed tomography (SPECT) and optical imaging. All of which are in current use in preclinical skeletal research. MRI can provide high resolution of soft tissue structures, but imaging requires comparatively long acquisition times; hence, animals require long-term anaesthesia. CT is extensively used in bone and joint disorders providing excellent spatial resolution and good contrast for bone imaging. Despite its excellent structural assessment of mineralized structures, CT does not provide in vivo functional information of ongoing biological processes. Nuclear medicine is a very promising tool for investigating functional and molecular processes in vivo with new tracers becoming available as biomarkers. The combined use of imaging modalities also holds significant potential for the assessment of disease pathogenesis in animal models of musculoskeletal disorders, minimising the use of conventional invasive methods and animal redundancy.

Interleukin-6 and chondrocyte mineralisation act in tandem to promote experimental osteoarthritis

“…We demonstrated that in the murine meniscectomy model of OA, calcium-containing crystal deposits were formed in the articular space prior to cartilage degradation (see online supplementary figure S1). These crystal deposits were previously identified as hypertrophic calcification,36 ectopic bone,37 mineralised area38 and heterotopic cartilage,39 but their chemical characterisation and their role in OA had never been determined. Starting from 1 month after OA induction, microCT-scan revealed multiple deposits within the joint, detached from bone, so that they could not be considered as osteophytes.…”

Induced superficial chondrocyte death reduces catabolic cartilage damage in murine posttraumatic osteoarthritis

“…For example, confocal microscopy provided 90% power to detect a 30% difference in superficial chondrocyte density using 4 specimens per group for the femoral head, humeral head, and lateral femoral condyle and 6 specimens per group for the medial femoral condyle (Supplemental Table 3). At present, the confocal imaging method is limited to ex vivo analyses of cartilage structure, a limitation shared with other highresolution imaging techniques such as μCT and μMRI (37,38).…”

Thallium Labeled Citrate-Coated Prussian Blue Nanoparticles as Potential Imaging Agent

“…This provides the ability of acquiring (almost) simultaneous in vivo images of highly resolved anatomy and accurately measured physiology in a noninvasive manner in animal models, clinical research, or diagnostics. This approach enables the explicit localization as well as the quantification of metabolic activity in target tissues [1, 2]. Nanoparticles embody unique imaging possibilities.…”