Estimating blood and brain concentrations and blood-to-brain influx by magnetic resonance imaging with step-down infusion of Gd-DTPA in focal transient cerebral ischemia and confirmation by quantitative autoradiography with Gd-[(14)C]DTPA.
An intravenous step-down infusion procedure that maintained a constant gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) blood concentration and magnetic resonance imaging (MRI) were used to localize and quantify the blood-brain barrier (BBB) opening in a rat model of transient cerebral ischemia (n=7). Blood-to-brain influx rate constant (K(i)) values of Gd-DTPA from such regions were estimated using MRI-Patlak plots and compared with the K(i) values of Gd-[(14)C]DTPA, determined minutes later in the same rats with an identical step-down infusion, quantitative autoradiography (QAR), and single-time equation. The normalized plasma concentration-time integrals were identical for Gd-DTPA and Gd-[(14)C]DTPA, indicating that the MRI protocol yielded reliable estimates of plasma Gd-DTPA levels. In six rats with a BBB opening, 14 spatially similar regions of extravascular Gd-DTPA enhancement and Gd-[(14)C]DTPA leakage, including one very small area, were observed. The terminal tissue-plasma ratios of Gd-[(14)C]DTPA tended to be slightly higher than those of Gd-DTPA in these regions, but the differences were not significant. The MRI-derived K(i) values for Gd-DTPA closely agreed and correlated well with those obtained for Gd-[(14)C]DTPA. In summary, MRI estimates of Gd-DTPA concentration in the plasma and brain and the influx rate are quantitatively and spatially accurate with step-down infusions.
Knight
Robert A
RA
Department of Neurology, Henry Ford Hospital, Detroit, Michigan 48202, USA. knight@neurnis.neuro.hfh.edu
Karki
Kishor
K
Ewing
James R
JR
Divine
George W
GW
Fenstermacher
Joseph D
JD
Patlak
Clifford S
CS
Nagaraja
Tavarekere N
TN