Nondestructive imaging of human cartilage glycosaminoglycan concentration by MRI

Despite the compelling need mandated by the prevalence and morbidity of deg enerative cartilage diseases, it is extremely difficult to study disease pr ogression and therapeutic efficacy, either in vitro or in vivo (clinically) , This is partly because no techniques have been available for nondestructi vely visualizing the distribution of functionally important macromolecules in living cartilage. Here we describe and validate a technique to image the glycosaminoglycan concentration ([GAG]) of human cartilage nondestructivel y by magnetic resonance imaging (MRI). The technique is based on the premis e that the negatively charged contrast agent gadolinium diethylene triamine pentaacetic acid (Gd(DTFA)(2.)) will distribute in cartilage in inverse re lation to the negatively charged GAG concentration. Nuclear magnetic resona nce spectroscopy studies of cartilage explants demonstrated that there was an approximately linear relationship between T-1 (in the presence of Gd(DTP A)(2-)) and [GAG] over a large range of [GAG], Furthermore, there was a str ong agreement between the [GAG] calculated from [Gd(DTPA)(2-)] and the actu al [GAG] determined from the validated methods of calculations from [Na+] a nd the biochemical DMMB assay. Spatial distributions of GAG were easily obs erved in T-1-weighted and T-1-calculated MRI studies of intact human joints , with good histological correlation. Furthermore, in vivo clinical images of T-1 in the presence of Gd(DTPA)(2-) (i.e., GAG distribution) correlated well with the validated ex vivo results after total knee replacement surger y, showing that it is feasible to monitor GAG distribution in vivo. This ap proach gives us the opportunity to image directly the concentration of GAG, a major and critically important macromolecule in human cartilage. Magn Re son Med 41:857-865, 1999. (C) 1999 Wiley-Liss, Inc.