Contrast enhanced micro-computed tomography (CEμCT) is a widely used, cost-efficient method for imaging soft tissues. For articular cartilage imaging, different stains are used to assess amount of cartilage constituents. Osteoarthritis progression can be monitored using CEμCT in clinical environment and laboratory.
In clinical modalities, ioxaglate (Hexabrix™) is used to indirectly assess proteoglycan content of cartilage. It is a iodine based anionic stain that has inversely proportional distribution to proteoglycan content. Collagen specific contrast agents are not in clinical use yet.
In vitro studies that evaluate osteoarthritis progression use histological staining as a gold standard method. Downside for this is long required time and destruction of sample for a thin, two-dimensional view of the sample. Alternatively, μCT could be used as a non-invasive tool for this when using a collagen stain. One such contrast agent is phosphotungstic acid. It has been shown to be able for three-dimensional evaluation of osteoarthritis grade in same manner as with histological stains.
Cationic contrast agent (CA4+) is used in vitro to assess proteoglycan content. It binds to glycosaminoglycan side chains while also slightly accumulating around chondrons. Its advantage is that it binds to target molecule giving accurate information about proteoglycan content when compared to other contrast agents.
Chondrocyte imaging with contrast agents is quite demanding. There is not a commonly accepted stain for chondrocytes up to date, but such dyes would be of high interest. Some potential stains might be gallocyanin chrome-alum or glucose-coated gold nanoparticles. A possible method for using gold nanoparticles is proposed in this thesis. There are also studies of chondron morphology using hexamethyldisilazane drying. Downside for this method is tissue shrinkage that might alter at least superficial chondrons.
Competing modalities for CEμCT include magnetic resonance imaging (MRI), Fourier transform infrared spectroscopy, near-infrared spectroscopy and Raman spectroscopy. In clinical environment MRI has clear advantage as it does not require utilization of ionizing radiation to produce great soft tissue contrast. High cost and low availability however are main limitations. Spectroscopic methods do not require contrast agents, but especially infrared spectroscopy requires extensive sample preparation and these methods provide only 2D maps of the sample.
Latest methods for desktop CEμCT cartilage imaging are reviewed in this thesis. Extracellular matrix assessing methods are studied in clinic and in vitro. Some chondrocyte imaging possibilities are discussed. CEμCT can be used to cost-effectively assess articular cartilage characteristics and OA progression in 3D
