title: MRI and quantitative autoradiographic studies following bolus injections of unlabeled and (14)C-labeled gadolinium-diethylenetriaminepentaacetic acid in a rat model of stroke yield similar distribution volumes and blood-to-brain influx rate constants.
abstract: 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.
authors.affiliation: Department of Anesthesiology, Henry Ford Hospital, Detroit, MI 48202, USA.
authors.forename: Tavarekere N
authors.initials: TN
authors.lastname: Nagaraja
authors.forename: James R
authors.initials: JR
authors.lastname: Ewing
authors.forename: Kishor
authors.initials: K
authors.lastname: Karki
authors.forename: Paul E
authors.initials: PE
authors.lastname: Jacobs
authors.forename: George W
authors.initials: GW
authors.lastname: Divine
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Fenstermacher
authors.forename: Clifford S
authors.initials: CS
authors.lastname: Patlak
authors.forename: Robert A
authors.initials: RA
authors.lastname: Knight
mesh_terms: D000818:Animals; D001345:Autoradiography / Q000379:methods*; D001812:Blood-Brain Barrier / Q000473:pathology; D001921:Brain / Q000473:pathology*; D002247:Carbon Isotopes; D004195:Disease Models, Animal; D019786:Gadolinium DTPA / Q000097:blood*; D007267:Injections; D007700:Kinetics; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling; D020521:Stroke / Q000097:blood* / Q000473:pathology
chemical_list: D002247:Carbon Isotopes; D019786:Gadolinium DTPA