Estimating blood and brain concentrations and blood-to-brain influx by magnetic resonance imaging with step-down infusion of Gd-DTPA in focal transient cerebral ischemia and confirmation by quantitative autoradiography with Gd-[14C]DTPA

An intravenous step-down infusion procedure that maintained a constant gadolinium-diethylene-triaminepentaacetic acid (Gd-DTPA) blood concentration and magnetic resonance imaging (MRI) were used to localize and quantify the blood-brain barrier (BBB) opening in a rat model of transient cerebral ischemia (n = 7). Blood-to-brain influx rate constant (K-i) values of Gd-DTPA from such regions were estimated using MRI-Patlak plots and compared with the K-i values of Gd-[C-14] DTPA, determined minutes later in the same rats with an identical step-down infusion, quantitative autoradiography (QAR), and single-time equation. The normalized plasma concentration-time integrals were identical for Gd-DTPA and Gd-[C-14] DTPA, indicating that the MRI protocol yielded reliable estimates of plasma Gd-DTPA levels. In six rats with a BBB opening, 14 spatially similar regions of extravascular Gd-DTPA enhancement and Gd-[C-14] DTPA leakage, including one very small area, were observed. The terminal tissue-plasma ratios of Gd-[C-14] DTPA tended to be slightly higher than those of Gd-DTPA in these regions, but the differences were not significant. The MRI-derived K-i values for Gd-DTPA closely agreed and correlated well with those obtained for Gd[C-14] DTPA. In summary, MRI estimates of Gd-DTPA concentration in the plasma and brain and the influx rate are quantitatively and spatially accurate with step-down infusions. Journal of Cerebral Blood Flow & Metabolism (2009) 29, 1048-1058; doi:10.1038/jcbfm.2009.20; published online 25 March 2009