on January 3, 2008
Published online before print January 3, 2008, doi: 10.1161/STROKEAHA.107.496059
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Submitted on June 12, 2007
From the Departments of Anesthesiology (T.N.N., R.L.C.) and Neurology (K.K., J.R.E., R.A.K.), Henry Ford Hospital, Detroit, Mich; and the Department of Physics (K.K., J.R.E., R.A.K.), Oakland University, Rochester, Mich. * To whom correspondence should be addressed. E-mail: annta{at}neuro.hfh.edu.
Background and Purpose—Variations in blood-brain barrier (BBB) opening after ischemia have been suggested by some tracer and magnetization transfer studies, although direct in vivo proof is still lacking. Contrast-enhanced magnetic resonance imaging (MRI) is also often used to visualize BBB damage in stroke. We hypothesized that MR contrast agents of different sizes enhance differently when BBB openings vary in size and that magnetization transfer alterations, measured by T1 in the presence of off-resonance radiofrequency saturation (T1sat), in these regions reflect such differences. Methods—Male Wistar rats ( Results—The Gd-BSA-EB–enhancing areas were always smaller (147±80 pixels) than those for Gd-DTPA (308±204 pixels) and were contained within the latter. The difference between the 2 areas was significant (P=0.024). Changes in T1sat were larger in Gd-BSA-EB–enhancing areas (ipsilateral to contralateral [I/C]=1.53±0.20) than in Gd-DTPA–enhancing areas (I/C=1.40±0.24, P=0.005). The differences in cerebral blood flow values between the 2 regions were not significant (P=0.62), but those for the Ki values of the 2 tracers were different (P=0.01 to 0.02). Excellent agreement between regions of Gd-BSA-EB enhancement and EB fluorescence was also observed. Conclusions—These results substantiate earlier reports of regional differences in BBB opening after stroke and provide the first in vivo evidence for this phenomenon. They also support the possible use of T1sat in quantifying stroke-induced graded BBB damage in the absence of contrast-enhanced MRI.
Accepted on July 3, 2007
Identification of Variations in Blood-Brain Barrier Opening After Cerebral Ischemia by Dual Contrast-Enhanced Magnetic Resonance Imaging and T1sat Measurements
Tavarekere N. Nagaraja PhD*;
300 g, n=7) were subjected to 3 hours of suture occlusion of the middle cerebral artery followed by reperfusion. Status of the BBB at 24 hours after the ictus was assessed first by Gd-DTPA (554 Da) MRI and then by Gd–bovine serum albumin linked to Evans blue (Gd-BSA-EB; 68 kDa) MRI for contrast enhancement; T1sat changes, cerebral blood flow, and blood-to-brain transfer constants (Kis) for the 2 contrast agents were measured. After MRI, rats were injected with fluorescent dextran and brains were studied by fluorescence microscopy.
Key words: blood-brain barrier • brain drug delivery • brain imaging • middle cerebral artery • neurovascular unit