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

摘要

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 3h of middle cerebral artery occlusion and 2.5h 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 Ki was slightly, but not significantly, higher for Gd-DTPA than for Gd-[~(14)C]DTPA. The Ki 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 Ki 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 Ki estimates based on such data are good quantitative indicators of BBB injury.