MRI and quantitative autoradiographic studies following bolus injections of unlabeled and 14C-labeled gadolinium-diethylenetriamine-pentaacetic acid in a rat model of stroke yield similar distribution volumes and blood-to-brain influx rate constants

In previous studies on a rat model of transient cerebral ischemia, the blood and brain concentrations of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) following intravenous bolus injection were repeatedly assessed by dynamic contrast-enhanced (DCE)-MRI, and blood-to-brain influx rate constants ( K i ) were calculated from Patlak plots of the data in areas with blood–brain barrier (BBB) opening. For concurrent validation of these findings, after completing the DCE-MRI study, radiolabeled sucrose or α-aminoisobutyric acid was injected intravenously, and the brain disposition and K i values were calculated by quantitative autoradiography (QAR) assay employing the single-time equation. To overcome two of the shortcomings of this comparison, the present experiments were carried out with a radiotracer virtually identical to Gd-DTPA, Gd-[ 14 C]DTPA, and K i was calculated from both sets of data by the single-time equation. The protocol included 3 h of middle cerebral artery occlusion and 2.5 h of reperfusion in male Wistar rats ( n = 15) preceding the DCE-MRI Gd-DTPA and QAR Gd-[ 14 C]DTPA measurements. In addition to K i , the tissue-to-blood concentration ratios, or volumes of distribution ( V R ), were calculated. The regions of BBB opening were similar on the MRI maps and autoradiograms. Within them, V R was nearly identical for Gd-DTPA and Gd-[ 14 C]DTPA, and K i was slightly, but not significantly, higher for Gd-DTPA than for Gd-[ 14 C]DTPA. The K i values were well correlated ( r = 0.67; p = 0.001). When the arterial concentration–time curve of Gd-DTPA was adjusted to match that of Gd-[ 14 C]DTPA, the two sets of K i values were equal and statistically comparable with those obtained previously by Patlak plots (the preferred, less model-dependent, approach) of the same data ( p = 0.2–0.5). These findings demonstrate that this DCE-MRI technique accurately measures the Gd-DTPA concentration in blood and brain, and that K i estimates based on such data are good quantitative indicators of BBB injury.