Assessment of T-1 and T*(2) effects in vivo and ex vivo using iron oxide nanoparticles in steady state-dependence on blood volume and water exchange

Accurate knowledge of the relationship between contrast agent concentration and tissue relaxation is a critical requirement for quantitative assessment of tissue perfusion using contrast-enhanced MRI. In the present study, using a pig model, the relationship between steady-state blood concentration levels of an iron oxide nanoparticle with a hydrated diameter of 12 nm (NC100150 Injection) and changes in the transverse and longitudinal relaxation rates (1/T-2* and 1/T-1, respectively) in blood, muscle, and renal cortex was investigated at 1.5 T. Ex vivo measurements of 1/T-2* and 1/T-1 were additionally performed in whole pig blood spiked with different concentrations of the iron oxide nanoparticle. In renal cortex and muscle, 1/T-2* increased linearly with contrast agent concentration with slopes of 101 +/- 22 s(-1) mM(-1) and 6.5 +/- 0.9 s(-1) mM(-1) (mean +/- SD), respectively. In blood, 1/T-2* increased as a quadratic function of contrast agent concentration, with different quadratic terms in the ex vivo vs. the in vivo experiments. In vivo, 1/T-1 in blood increased linearly with contrast agent concentration, with a slope (T-1-relaxivity) of 13.9 +/- 0.9 s(-1) mM(-1). The achievable increase in 1/T-1 in renal cortex and muscle was limited by the rate of water exchange between the intra- and extravascular compartments and the 1/T-1-curves were well described by a two-compartment water exchange limited relaxation model. (C) 2002 Wiley-Liss, Inc.