Quantitation and localization of blood-to-brain influx by magnetic resonance imaging and quantitative autoradiography in a model of transient focal ischemia

Abstract

The ability of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) enhanced MRI to localize and quantitate blood-brain barrier (BBB) opening was evaluated against quantitative autoradiographic (QAR) imaging of 14C-α-aminoisobutyric acid (AIB) distribution. The blood-to-brain transfer constant (Ki) for Gd-DTPA was determined by MRI in rats after 3 h of focal cerebral ischemia plus 2.5 h of reperfusion (n = 9), and that of AIB was determined by QAR shortly thereafter. Tissue regions of interest (ROIs) for Gd-DTPA leakage were identified by ISODATA segmentation of pre- and post-Gd-DTPA Look-Locker (L-L) T1 maps. Patlak plots were constructed using time course of blood and tissue T1 changes induced by Gd for estimating Ki. Among the nine rats, 14 sizable regions of AIB uptake were found; 13 were also identified by ISODATA segmentation. Al-though the 13 MRI-ROIs spatially approximated those of AIB uptake, the segmentation sometimes missed small areas of lesser AIB uptake that did not extend through more than 60% of the 2.0-mm-thick slice. Mean Ki's of AIB were highly correlated with those of Gd-DTPA across the 13 regions; the group means (±SD) were similar for the two tracers (7.1 ± 3.3 × 10 -3 and 6.8 ± 3.5 × 10-3 ml.g-1 · min-1, respectively). In most instances, Gd-DTPA MRI accurately localized areas of BBB opening. © 2005 Wiley-Liss, Inc.