**14. Evaluation of the Aggrecan Content and Distribution in Pathological Cartilage Using Imaging Techniques**

This review shows that aggrecan is an important functional component of articular cartilage and is depleted in OA cartilage. Several non-invasive cartilage imaging procedures have been developed that allow the assessment of the spatiotemporal distribution of aggrecan during OA disease progression. MRI of articular cartilage (AC) has been applied to assess osteoarthritic changes occurring in cartilage with the progression of OA. Traditional MRI evaluates AC morphology and measures cartilage thickness over time [249]. More advanced MRI techniques can now be used to assess AC matrix composition non-invasively to detect early articular changes. T2-mapping and T1ρ sequences estimate the relaxation times of water inside AC and have found application in clinical protocols to assess cartilage changes in OA [250]. Diffusion-weighted and diffusion tensor imaging can also be used to assess ECM changes in AC since the movement of water in cartilage is affected by ECM composition and structure. Specific imaging techniques that evaluate cartilage GAGs, such as delayed gadolinium enhanced MRI [251] or Chemical Exchange Saturation Transfer [252,253] and sodium imaging [254,255] or PET (positron emission tomography)-sodium imaging [256] have also shown utility in the non-invasive detection of AC damage [257].
