Relaxivity and diffusion of gadolinium agents in cartilage

Prior work indicates that the distribution of Gd(DTPA)(2-) (as measured by T-1) is a good surrogate measure of the distribution of gycosaminoglycan (GAG) in cartilage. In addition to the measured T-1 in the presence of Gd(DTPA)(2-), the precision of the measurement of Gd(DTPA)(2-) concentration depends on the T-1 without Gd(DTPA)(2-) (T(1)degrees), and the relaxivity (r) of Gd(DTPA)(2-) in cartilage, parameters that are influenced by cartilage composition. These parameters were measured in native and GAG-depleted cartilage in order to estimate the bounds on the values one might expect for cartilage in arbitrary states of degeneration. The range of T(1)degrees was 0.3 sec; the range of r was 0.6 (mM*s)(-1) at 8.5 T and 1.4 (mM*s)(-1) at 2 T. These data suggest that Gd(DTPA)(2-) will be underestimated (and GAG overestimated) if the values for T(1)degrees, and r are assumed to be those of native cartilage. (For example, in a severe case a 90% loss of GAG would be underestimated as a 70% loss.) Gd(HPDO3A) was investigated as a nonionic "control agent" and found to have relaxivity and diffusion properties that were comparable to Gd(DTpA)(2-) (r(GD(HPDO3A))/r(Gd(DTPA)) approximate to 1; D-Gd(HPDO3A)/D-Gd(DTPA) approximate to 0.85). Since Gd(HPDO3A) distributes uniformly through cartilage (independent of GAG), the distribution of T-1 with Gd(HPDO3A) can be used as a surrogate measure of variations in T(1)degrees and r, if present. From the perspective of transport, if Gd(HPDO3A) has fully penetrated the cartilage, Gd(DTPA)(2-) would have in the same time frame. Therefore, the data confirm the efficacy of using Gd(HPDO3A) as a "control agent" for dGEMRIC.