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

作者：Nagaraja Tavarekere N^*; Ewing James R; Karki Kishor; Jacobs Paul E; Divine George W; Fenstermacher Joseph D; Patlak Clifford S; Knight Robert A

来源：NMR in Biomedicine, 2011, 24(5): 547-558.

DOI：10.1002/nbm.1625

• arterial input function
• blood-brain barrier
• cerebral blood flow
• cerebral ischemia
• DCE-MRI
• magnetic resonance contrast agents
• neurovascular unit
• Patlak plot

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 (Ki) 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 a-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-[C-14] 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-[C-14] DTPA measurements. In addition to Ki, 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-[C-14]DTPA, and Ki was slightly, but not significantly, higher for Gd-DTPA than for Gd-[C-14] 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-[C-14] 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.

• 出版日期2011-6