Identification of Variations in Blood-Brain Barrier Opening After Cerebral Ischemia by Dual Contrast-Enhanced Magnetic Resonance Imaging and T 1sat Measurements

Abstract

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 T 1 in the presence of off-resonance radiofrequency saturation (T 1sat ), in these regions reflect such differences. Methods— Male Wistar rats (≈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; T 1sat changes, cerebral blood flow, and blood-to-brain transfer constants ( K i s) for the 2 contrast agents were measured. After MRI, rats were injected with fluorescent dextran and brains were studied by fluorescence microscopy. 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 T 1sat 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 K i 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 T 1sat in quantifying stroke-induced graded BBB damage in the absence of contrast-enhanced MRI.