In Vivo Monitoring of Joint Cartilage – Lessons to Be Learned by Delayed Gadolinium Enhanced Magnetic Resonance Imaging of Cartilage

Leif E Dahlberg, Eveliina Lammentausta, Carl Johan Tiderius, Miika T Nieminen
European Musculoskeletal Review, 2012;7(1):58-62
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Abstract

Understanding the pathogenesis of osteoarthritis is fundamental for developing cause-related treatment strategies. This requires biomarkers that enable the detection of tissue changes in early disease. Delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) has been proposed for the estimation of cartilage glycosaminoglycan (GAG) content. With sufficient post-contrast delay, allowing full equilibration, the technique reflects cartilage GAG content in vitro. In the in vivo realm, equilibrium is not achieved, making the technique sensitive to other factors besides GAG. While the specificity of dGEMRIC to GAG content may be compromised, it appears to be a sensitive biomarker to reveal early degenerative changes in cartilage quality.
Keywords
Delayed gadolinium-enhanced magnetic resonance imaging of cartilage, glycosaminoglycan, magnetic resonance imaging, cartilage, monitoring
Disclosure The authors have no conflicts of interest to declare.
Received: December 22, 2011 Accepted January 24, 2012
Correspondence: Leif Dahlberg, Professor Joint and Soft Tissue Unit Department of Clinical Sciences, Malmö Lund University Department of Orthopaedics Skåne University Hospital SE-205 02 Malmö, Sweden. E: leif.dahlberg@med.lu.se

Understanding the pathogenesis of our most common joint disorder, osteoarthritis (OA), is fundamental for developing cause-related treatment strategies. The hallmark of the OA joint is cartilage loss, which, when present together with joint pain, defines knee OA. Clearly, the pathological processes have started many years before cartilage loss is seen on radiographs. Interventions need to be carried out early enough to prevent irreversible cartilage changes and cartilage loss. So far, our limited access to methods capable of detecting joint cartilage molecular alterations in the pre-radiographic course of OA has hampered the identification of individuals at risk of OA, as well as the development of effective treatments.

The extracellular matrix of articular cartilage consists of two main macromolecules, type II collagen and the large aggregating proteoglycan aggrecan. The collagen fibril is a heteropolymer primarily composed of type II collagen, with small amounts of types IX and XI collagens.1 Aggrecan, with its highly negatively charged glycosaminoglycans (GAGs), can bind up to 50 times its weight in water, resulting in a swelling pressure that is normally constrained by the tensile strength of the collagen fibrillar network.2 This interaction is the key mechanism behind the viscoelastic properties of articular cartilage that provide joints with the necessary resistance to mechanical loading. For a long time it has been known that cartilage GAG content is related to the tissue fixed charge density (FCD), which in turn is related to cartilage biomechanical properties.2,3 This has generated efforts to estimate cartilage GAG content and FCD in vivo. A method that holds promise in this respect is using a paramagnetic negatively charged contrast agent that, after intravenous injection, distributes into the cartilage inversely to cartilage negative charge. Using this method, delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC), both in vitro and in cross-sectional and longitudinal patient cohorts, has considerably increased our knowledge of the relationship between exogenous factors and structural molecular cartilage changes that are related to GAG in joint health and pre-radiographic disease.

Osteoarthritis Pathogenesis

The risk of knee OA is associated with meniscectomy, obesity, muscle weakness and major injury, whereas hip OA is commonly associated with congenital and developmental defects such as acetabular dysplasia and possibly obesity.4,5 In addition, age is generally considered a risk factor for OA; however, knee and hip OA incidence has not been convincingly shown to increase with ageing.4,6

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