The Transport of Anionic and Nonionic MRI Contrast Agents into Human Hip Cartilage

INTRODUCTION Delayed gadolinium enhanced MRI of cartilage (dGEMRIC) is a quantitative MRI method utilizing anionic contrast agent Gd-DTPA. The suggested mechanism is that the fixed charge density (FCD) of cartilage, induced by glycosaminoglycans (GAG), dictates the contrast agent distribution in cartilage via electrostatic repulsion [1]. The aim of the present study was to investigate the difference between transport of anionic and nonionic contrast agent into human hip cartilage. METHODS Two MRI contrast agents, namely anionic Gd-DTPA (Magnevist, Bayer Schering Pharma AG, Berlin, Germany), and nonionic Gd-DTPA-BMA (Omniscan, GE Healthcare, Milwaukee, WI, USA) were used. Human femoral heads (n=8, age: 79±7, range 65-88) were harvested from patients undergoing hip replacement surgery due to hip fracture. The cartilage was visually intact. Two adjacent osteochondral plugs (diameter=4mm) were detached from weight-bearing region, one plug to be investigated using each contrast agent. A 200MHz (4.7T) spectrometer (Bruker Avance-II) was used to obtain profile images from the samples in depth-wise direction. First, T1 relaxation time was measured without contrast agent (inversion recovery sequence, TR=5 s, 16 TI’s between 1 and 1000 ms, depth-wise resolution of 20 μm). Subsequently, the samples were exposed to 2mM solution of contrast agent. Due to test tube geometry the contrast agent could transport into the cartilage through cartilage surface only. After this, T1 was measured with 25 minutes intervals until ten hours. The change in relaxation rate (ΔR1), reflecting the contrast agent concentration, was calculated for each time point, and the cartilage depth was normalized. Mean values of ΔR1 were calculated as a depth-wise profile after ten hours of contrast agent exposure, and as time-dependent curves at the most superficial, middle and deep cartilage (each ROI included 1/20 of total cartilage thickness). The difference between the ΔR1’s was tested with Mann-Whitney U test for each time and depth. RESULTS After ten hours of equilibration, the ΔR1 for Gd-DTPA-BMA was significantly higher than that for Gd-DTPA at all depths (Figure 1). Both profiles displayed decreasing ΔR1 towards deep cartilage, but for Gd-DTPA the depth-wise decrease was faster near the surface, whereas for Gd-DTPA-BMA it was faster in the deep cartilage. For superficial cartilage, Gd-DTPA reaches maximum concentration relatively fast, around two hours, whereas Gd-DTPA-BMA hasn’t reached equilibrium in ten hours (Figure 2a). In the beginning, the concentration of Gd-DTPA is higher, but eventually Gd-DTPA-BMA reaches higher concentrations with a significant difference from six hours onwards. For middle cartilage the concentrations are similar in the beginning, but Gd-DTPA-BMA reaches higher concentration (Figure 2b). Significant difference is displayed already after two hours. For deep cartilage, the situation is similar with lower concentrations and significant difference from three hours onwards (Figure 2c).