title: Assessment of T1 and T2* effects in vivo and ex vivo using iron oxide nanoparticles in steady state--dependence on blood volume and water exchange.
abstract: 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/T2* and 1/T1, respectively) in blood, muscle, and renal cortex was investigated at 1.5 T. Ex vivo measurements of 1/T2* and 1/T1 were additionally performed in whole pig blood spiked with different concentrations of the iron oxide nanoparticle. In renal cortex and muscle, 1/T2* 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/T2* 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/T1 in blood increased linearly with contrast agent concentration, with a slope (T1-relaxivity) of 13.9 +/- 0.9 s(-1)mM(-1). The achievable increase in 1/T1 in renal cortex and muscle was limited by the rate of water exchange between the intra- and extravascular compartments and the 1/T1-curves were well described by a two-compartment water exchange limited relaxation model.
authors.affiliation: Nycomed Imaging AS, Oslo, Norway. atle.bjornerud@rikshospitalet.no
authors.forename: Atle
authors.initials: A
authors.lastname: Bjørnerud
authors.forename: Lars O
authors.initials: LO
authors.lastname: Johansson
authors.forename: Karen
authors.initials: K
authors.lastname: Briley-Saebø
authors.forename: Håkan K
authors.initials: HK
authors.lastname: Ahlström
mesh_terms: D000818:Animals; D001810:Blood Volume; D001834:Body Water / Q000378:metabolism; D003287:Contrast Media / Q000493:pharmacokinetics*; D003911:Dextrans; D052203:Ferrosoferric Oxide; D007091:Image Processing, Computer-Assisted; D007501:Iron / Q000493:pharmacokinetics*; D007672:Kidney Cortex / Q000033:anatomy & histology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D009132:Muscles / Q000033:anatomy & histology*; D036103:Nanotechnology; D010087:Oxides / Q000493:pharmacokinetics*; D010316:Particle Size; D013552:Swine
chemical_list: D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; C097921:ferumoxtran-10; D007501:Iron; D052203:Ferrosoferric Oxide