Characterization of viscosupplementation formulations using chemical exchange saturation transfer (ViscoCEST)

BACKGROUND: Osteoarthritis (OA) is characterized by progressive loss of cartilage in joints, and is a major cause of pain and disability, and imposes significant health care expense. New therapies are being developed to treat the symptomatic effect of OA, one of which is intra-articular injection of viscosupplementations of different forms of hyaluronic acid (HA). The current study evaluates the chemical exchange saturation transfer (CEST) effect from two popular viscosupplementations [Hylan gf-20 (Synvisc) and hyaluronan (Orthovisc)] by targeting the exchangeable hydroxyl protons present on these molecules (ViscoCEST). METHODS: ViscoCEST imaging from two viscosupplementations (Synvisc and Orthovisc) was performed on a 7T Siemens whole body MRI scanner. ViscoCEST images were collected with different combination of saturation pulse power and saturation duration. Z spectra were acquired at B(1rms) of 3.6 μT and 1 s saturation duration by varying the frequency from −4 to +4 ppm in step size of 0.1 ppm. Field inhomogeneity (B(0)) and radiofrequency (B(1)) maps were also acquired to correct ViscoCEST contrast map for any inhomogeneity. RESULTS: Both viscosupplementations showed broad CEST effect (ViscoCEST), which peaked ~0.8 ppm from down field of water resonance. Orthovisc showed 20 % higher ViscoCEST contrast than Synvisc suggestive of more HA component in Orthovisc. Increased ViscoCEST contrast was observed from both viscosupplementations with increase in B(1rms) and saturation pulse duration. CONCLUSION: ViscoCEST has a potential to image the spatial distribution of viscosupplements in vivo in patients’ intra-articular space as well as temporal variation in their spatial distribution.