Development of a Minimally Invasive Method to Assess Glycosaminoglycan Content for Early Diagnosis of Osteoarthritis

Abstract

Purpose: Osteoarthritis (OA) is a painful degenerative joint disease that affects over 30 million people worldwide. By the time patients present with either clinical or radiographic signs of OA, they typically have advanced disease. It has been shown that the depletion of glycosaminoglycans (GAG) within articular cartilage is key to the pathogenesis of OA and begins long before patients experience symptoms. The purpose of this project is to develop a minimally invasive method of assessing the GAG content of cartilage that can eventually be used as a screening tool for patients at risk of developing OA. Methods: Several phantom compounds that are biomimetic are articular cartilage were created to simulate a range of GAG concentrations that are analogous to the concentrations found in diseased and healthy joints. The phantoms were exposed to a positively charged, iodinated contrast agent (CA4+) for varying time intervals and assessed using Contrast-Enhanced Computed Tomography (CECT). CT attenuation values (in HU) were expected to correlate to a specific GAG concentration in each phantom. Phantom compounds made from Tisseel (a synthetic fibrin matrix), synthetic collagen and chondroitin sulfate (PureCol-C4S), and synthetic collagen and bovine cartilage (PureCol-BC) were assessed with CECT at GAG percent by weight of 2.5%, 5%, 7.5%, and 10%, after exposure to contrast for 1 hour, 4 hours, and 20 hours. Results: Tisseel-based phantoms demonstrated qualitatively increased uptake of contrast with increased percent-by-weight GAG, but showed gross matrix degradation hours after exposure to contrast, limiting study capability. PureCol-C4S phantoms at equilibrium (20 hours) showed the following CT attenuations (in HU) by weight of GAG; Control: 1096, 2.5%: 8796, 5%: 10298, 7.5%: 5481, 10%: 11837. PureCol-BC phantoms at equilibrium showed the following CT attenuations (in HU); Control: 1082.25, Low GAG: 1633.14, Medium GAG: 1535.57, High GAG: 1916.29 (R2=0.803). Conclusions: A phantom biomimetic to articular cartilage demonstrates qualitatively increased CECT attenuation when exposed to CA4+ with increasing GAG content. A more stable phantom and larger sample size is necessary to establish an appropriate quantitative relationship.